Targeted delivery of photosensitizers: efficacy and selectivity issues revealed by multifunctional ORMOSIL nanovectors in cellular systems

PEGylated and non-PEGylated ORMOSIL nanoparticles prepared by microemulsion condensation of vinyltriethoxy-silane (VTES) were investigated in detail for their micro-structure and ability to deliver photoactive agents. With respect to pure silica nanoparticles, organic modification substantially changes the microstructure and the surface properties. This in turn leads to a modulation of both the photophysical properties of embedded photosensitizers and the interaction of the nanoparticles with biological entities such as serum proteins. The flexibility of the synthetic procedure allows the rapid preparation and screening of multifunctional nanosystems for photodynamic therapy (PDT). Selective targeting of model cancer cells was tested by using folate, an integrin specific RGD peptide and anti-EGFR antibodies. Data suggest the interference of the stealth-conferring layer (PEG) with small targeting agents, but not with bulky antibodies. Moreover, we showed that selective photokilling of tumour cells may be limited even in the case of efficient targeting because of intrinsic transport limitations of active cellular uptake mechanisms or suboptimum localization

Sheets of vertically aligned BaTiO₃ nanotubes reduce cell proliferation but not viability of NIH-3T3 cells

All biomaterials initiate a tissue response when implanted in living tissues. Ultimately this reaction causes fibrous encapsulation and hence isolation of the material, leading to failure of the intended therapeutic effect of the implant. There has been extensive bioengineering research aimed at overcoming or delaying the onset of encapsulation. Nanotechnology has the potential to address this problem by virtue of the ability of some nanomaterials to modulate interactions with cells, thereby inducing specific biological responses to implanted foreign materials. To this effect in the present study, we have characterised the growth of fibroblasts on nano-structured sheets constituted by BaTiO3, a material extensively used in biomedical applications. We found that sheets of vertically aligned BaTiO3 nanotubes inhibit cell cycle progression - without impairing cell viability - of NIH-3T3 fibroblast cells. We postulate that the 3D organization of the material surface acts by increasing the availability of adhesion sites, promoting cell attachment and inhibition of cell proliferation. This finding could be of relevance for biomedical applications designed to prevent or minimize fibrous encasement by uncontrolled proliferation of fibroblastic cells with loss of material-tissue interface underpinning long-term function of implants

A coherent polarimeter array for the Large Scale Polarization Explorer balloon experiment

We discuss the design and expected performance of STRIP (STRatospheric Italian Polarimeter), an array of coherent receivers designed to fly on board the LSPE (Large Scale Polarization Explorer) balloon experiment. The STRIP focal plane array comprises 49 elements in Q band and 7 elements in W-band using cryogenic HEMT low noise amplifiers and high performance waveguide components. In operation, the array will be cooled to 20 K and placed in the focal plane of a $\sim 0.6$ meter telescope providing an angular resolution of $\sim1.5$ degrees. The LSPE experiment aims at large scale, high sensitivity measurements of CMB polarization, with multi-frequency deep measurements to optimize component separation. The STRIP Q-band channel is crucial to accurately measure and remove the synchrotron polarized component, while the W-band channel, together with a bolometric channel at the same frequency, provides a crucial cross-check for systematic effects.Comment: In press on the Proceedings of the SPIE Conference Astronomical Telescopes + instrumentation 2012, Amsterdam, paper 8446-27

Acute immune signatures and their legacies in severe acute respiratory syndrome coronavirus-2 infected cancer patients

Given the immune system’s importance for cancer surveillance and treatment, we have investigated how it may be affected by SARS-CoV-2 infection of cancer patients. Across some heterogeneity in tumor type, stage, and treatment, virus-exposed solid cancer patients display a dominant impact of SARS-CoV-2, apparent from the resemblance of their immune signatures to those for COVID-19+ non-cancer patients. This is not the case for hematological malignancies, with virus-exposed patients collectively displaying heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus shedding. Furthermore, while recovered solid cancer patients’ immunophenotypes resemble those of nonvirus-exposed cancer patients, recovered hematological cancer patients display distinct, lingering immunological legacies. Thus, while solid cancer patients, including those with advanced disease, seem no more at risk of SARS-CoV-2-associated immune dysregulation than the general population, hematological cancer patients show complex immunological consequences of SARS-CoV-2 exposure that might usefully inform their care

QUBIC: the Q&U Bolometric Interferometer for Cosmology

The primordial B-mode polarisation of the Cosmic Microwave Background is the imprints of the gravitational wave background generated by inflation. Observing the B-mode is up to now the most direct way to constrain the physics of the primordial Universe, especially inflation. To detect these B-modes, high sensitivity is required as well as an exquisite control of systematics effects. To comply with these requirements, we propose a new instrument called QUBIC (Q and U Bolometric Interferometer for Cosmology) based on bolometric interferometry. The control of systematics is obtained with a close-packed interferometer while bolometers cooled to very low temperature allow for high sensitivity. We present the architecture of this new instrument, the status of the project and the self-calibration technique which allows accurate measurement of the instrumental systematic effects

Putting the Pieces Together: Integrative Modeling Platform Software for Structure Determination of Macromolecular Assemblies

A set of software tools for building and distributing models of macromolecular assemblies uses an integrative structure modeling approach, which casts the building of models as a computational optimization problem where information is encoded into a scoring function used to evaluate candidate models

Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization

Combining genome-wide structural models with phenomenological data is at the forefront of efforts to understand the organizational principles regulating the human genome. Here, we use chromosome-chromosome contact data as knowledge-based constraints for large-scale three-dimensional models of the human diploid genome. The resulting models remain minimally entangled and acquire several functional features that are observed in vivo and that were never used as input for the model. We find, for instance, that gene-rich, active regions are drawn towards the nuclear center, while gene poor and lamina associated domains are pushed to the periphery. These and other properties persist upon adding local contact constraints, suggesting their compatibility with non-local constraints for the genome organization. The results show that suitable combinations of data analysis and physical modelling can expose the unexpectedly rich functionally-related properties implicit in chromosome-chromosome contact data. Specific directions are suggested for further developments based on combining experimental data analysis and genomic structural modelling

QUBIC instrument for CMB polarization measurements

Measurements of cosmic microwave background (CMB) polarization may reveal the presence of a background of gravitational waves produced during cosmic inflation, providing thus a test of inflationary models. The Q&U Bolometric Interferometer for Cosmology (QUBIC) is an experiment designed to measure the CMB polarization. It is based on the novel concept of bolometric interferometry, which combines the sensitivity of bolometric detectors with the properties of beam synthesis and control of calibration offered by interferometers. To modulate and extract the input polarized signal of the CMB, QUBIC exploits Stokes polarimetry based on a rotating half-wave plate (HWP). In this work, we illustrate the design of the QUBIC instrument, focusing on the polarization modulation system, and we present preliminary results of beam calibrations and the performance of the HWP rotator at 300 K