Multistage nanovectors: from concept to novel imaging contrast agents and therapeutics

Over the last few decades a great variety of nanotechnology based platforms have been synthesized and fabricated to improve the delivery of active compounds to a disease site. Nanoparticles currently used in the clinic, and the majority of nanotherapeutics/nanodiagnostics under investigation, accommodate single- or multiple- functionalities on the same entity. Because many heterogeneous biological barriers can prevent therapeutic and imaging agents from reaching their intended targets in sufficient concentrations, there is an emerging requirement to develop a multimodular nanoassembly, in which different components with individual specific functions act in a synergistic manner. The multistage nanovectors (MSVs) were introduced in 2008 as the first system of this type. It comprises several nanocomponents or "stages", each of which is designed to negotiate one or more biological barriers. Stage 1 mesoporous silicon particles (S1MPs) were rationally designed and fabricated in a nonspherical geometry to enable superior blood margination and to increase cell surface adhesion. The main task of S1MPs is to efficiently transport nanoparticles that are loaded into their porous structure and to protect them during transport from the administration site to the disease lesion. Semiconductor fabrication techniques including photolithography and electrochemical etching allow for the exquisite control and precise reproducibility of S1MP physical characteristics such as geometry and porosity. Furthermore, S1MPs can be chemically modified with negatively/positively charged groups, PEG and other polymers, fluorescent probes, contrast agents, and biologically active targeting moieties including antibodies, peptides, aptamers, and phage. The payload nanoparticles, termed stage 2 nanoparticles (S2NPs), can be any currently available nanoparticles such as liposomes, micelles, inorganic/metallic nanoparticles, dendrimers, and carbon structures, within the approximate size range of 5-100 nm in diameter. Depending upon the physicochemical features of the S1MP (geometry, porosity, and surface modifications), a variety of S2NPs or nanoparticle "cocktails" can be loaded and efficiently delivered to the disease site. As demonstrated in the studies reviewed here, once the S2NPs are loaded into the S1MPs, a variety of novel properties emerge, which enable the design of new and improved imaging contrast agents and therapeutics. For example, the loading of the MRI Gd-based contrast agents onto hemispherical and discoidal S1MPs significantly increased the longitudal relaxivity (r1) to values of up to 50 times larger than those of clinically available gadolinium-based agents (~4 mM(-1) s(-1)/Gd(3+) ion). Furthermore, administration of a single dose of MSVs loaded with neutral nanoliposomes containing small interfering RNA (siRNA) targeted against the EphA2 oncoprotein enabled sustained EphA2 gene silencing for at least 21 days. As a result, the tumor burden was reduced in an orthotopic mouse model of ovarian cancer. We envision that the versatility of the MSV platform and its emerging properties will enable the creation of personalized solutions with broad clinical implications within and beyond the realm of cancer theranostics.     

Matching economical, energetic and environmental benefits: An analysis for hybrid CHCP-heat pump systems

The optimization of design and operation of combined heat, cooling and power systems usually leads to select different plant lay-outs and size of components, depending on the adopted optimization criterion (maximum profit or energy saving or minimum environmental impact). This occurs when the current energy prices and the normative provisions supporting cogeneration are not able to coincide with the specific customer’s interest and the overall “social interest” for a reduction in energy consumption and in pollutants’ emissions. At EU level, polygeneration is considered to have a large potential for residential and commercial buildings district network, for the tertiary sector and for industrial applications. In such applications, it is often convenient to integrate the trigeneration system with a reversible heat pump, because of a low ratio between electric demand and that for heating and cooling. In this paper, the design and operation of such hybrid systems is discussed. The results achievable through different operation modes are compared and, with reference to a 600-rooms hotel and a 300-beds hospital in Italy, the effects on plant design from an hour-by-hour optimization of plant operation are assessed. Finally, the need for a flexible support system for cogeneration plants is put into evidence and some criteria are listed for an effective regulation.     

Technical and economical analysis of a solar–geothermal hybrid plant based on an Organic Rankine Cycle

A combined concentrating solar power system and a geothermal binary plant based on an Organic Rankine Cycle (ORC) is analyzed. Given a supercritical ORC, designed for the optimal utilization of an intermediate enthalpy geothermal source, a solar parabolic trough field was included in the plant, introducing an additional high temperature heat source for the cycle and increasing power production. The off-design performance analysis of the power cycle was performed first. An hour-by-hour simulation was then carried out to estimate the yearly production using a detailed solar field model. Finally, a differential economic analysis was performed to determine the cost of the additional electricity generated with the solar source. On the basis of the current cost of solar collectors, levelized costs of electricity of 145-280 €/MWh were obtained depending on the location of the plant: a competitive value with respect to large, stand-alone concentrating solar power plants.     

A neural theory of attentive visual search: Interactions of boundary, surface, spatial, and object representations.

Visual search data are given a unified quantitative explanation by a model of how spatial maps in the parietal cortex and object recognition categories in the inferotemporal cortex deploy attentional resources as they reciprocally interact with visual representations in the prestriate cortex. The model visual representations are organized into multiple boundary and surface representations. Visual search in the model is initiated by organizing multiple items that lie within a given boundary or surface representation into a candidate search grouping. These items are compared with object recognition categories to test for matches or mismatches. Mismatches can trigger deeper searches and recursive selection of new groupings until a target object is identified. The model provides an alternative to Feature Integration and Guided Search models. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tailings-nonwoven geotextile filter compatibility in mining applications

Nonwoven geotextiles have been commonly used in filtration and drainage of geotechnical engineering works. This paper presents a study on the use of such materials in drainage and filtration systems of tailings dams. Different combinations of tailings and geotextiles were submitted to gradient ratio (GR) tests under confinement in the laboratory with varying values of stress levels and hydraulic gradients. The results of GR tests under confining stresses up to 2000 kPa are presented and discussed. The dimensions of the tailings particles entrapped in the geotextile specimens and those that piped through the geotextile were also assessed. Geotextile specimens from the drainage system of a tailings dam were exhumed for analyses, as part of the research programme. The results obtained showed that stress levels and the hydraulic gradients used in the tests influenced the behaviour of the system. Physical and microscopic analyses of the specimens tested showed greater geotextile impregnation by tailings particles in the field than in the laboratory. The overall performance of the geotextiles tested under laboratory conditions was satisfactory. However, in the field segregation of tailings particles and transport of fines in suspension can subject the filter to more complex and severe clogging mechanisms, not properly simulated in current standard testing procedures.     

Controlling DNA Bundle Size and Spatial Arrangement in Self-assembled Arrays on Superhydrophobic Surface

Nano-Micro Letters - The use of superhydrophobic surfaces (SHSs) is now emerging as an attractive platform for the realization of one-dimensional (1D) nanostructures with potential applications in...