Intratumoral Thermal Reading During Photo‐Thermal Therapy by Multifunctional Fluorescent Nanoparticles

The tremendous development of nanotechnology is bringing us closer to the dream of clinical application of nanoparticles in photothermal therapies of tumors. This requires the use of specific nanoparticles that must be highly biocompatible, efficient light‐to‐heat converters and fluorescent markers. Temperature reading by the heating nanoparticles during therapy appears of paramount importance to keep at a minimum the collateral damage that could arise from undesirable excessive heating. In this work, this thermally controlled therapy is possible by using Nd³⁺ ion‐doped LaF₃ nanocrystals. Because of the particular optical features of Nd³⁺ ions at high doping concentrations, these nanoparticles are capable of in vivo photothermal heating, fluorescent tumor localization and intratumoral thermal sensing. The successful photothermal therapy experiments here presented highlight the importance of controlling therapy parameters based on intratumoral temperature measurements instead of on the traditionally used skin temperature measurements. In fact, significant differences between intratumoral and skin temperatures do exist and could lead to the appearance of excessive collateral damage. These results open a new avenue for the real application of nano­particle‐based photothermal therapy at clinical level.     

A VLIW processor with reconfigurable instruction set for embedded applications

This paper describes a new architecture for embedded reconfigurable computing, based on a very-long instruction word (VLIW) processor enhanced with an additional run-time configurable datapath. The reconfigurable unit is tightly coupled with the processor, featuring an application-specific instruction-set extension. Mapping computation intensive algorithmic portions on the reconfigurable unit allows a more efficient elaboration, thus leading to an improvement in both timing performance and power consumption. A test chip has been implemented in a standard 0.18-/spl mu/m CMOS technology. The test of a signal processing algorithmic benchmark showed speedups ranging from 4.3/spl times/ to 13.5/spl times/ and energy consumption reduced up to 92%.     

Evolution of silicon bulk lifetime during III–V‐on‐Si multijunction solar cell epitaxial growth

The evolution of Si bulk minority carrier lifetime during the heteroepitaxial growth of III–V on Si multijunction solar cell structures via metal‐organic chemical vapor deposition (MOCVD) has been analyzed. In particular, the impact on Si lifetime resulting from the four distinct phases within the overall MOCVD‐based III–V/Si growth process were studied: (1) the Si homoepitaxial emitter/cap layer; (2) GaP heteroepitaxial nucleation; (3) bulk GaP film growth; and (4) thick GaAs_yP_1‐y compositionally graded metamorphic buffer growth. During Phase 1 (Si homoepitaxy), an approximately two order of magnitude reduction in the Si minority carrier lifetime was observed, from about 450 to ≤1 µs. However, following the GaP nucleation (Phase 2) and thicker film (Phase 3) growths, the lifetime was found to increase by about an order of magnitude. The thick GaAs_yP_1‐y graded buffer was then found to provide further recovery back to around the initial starting value. The most likely general mechanism behind the observed lifetime evolution is as follows: lifetime degradation during Si homoepitaxy because of the formation of thermally induced defects within the Si bulk, with subsequent lifetime recovery due to passivation by fast‐diffusing atomic hydrogen coming from precursor pyrolysis, especially the group‐V hydrides (PH₃, AsH₃), during the III–V growth. These results indicate that the MOCVD growth methodology used to create these target III–V/Si solar cell structures has a substantial and dynamic impact on the minority carrier lifetime within the Si substrate. Copyright © 2015 John Wiley & Sons, Ltd.     

Active Materials for 3D Printing in Small Animals: Current Modalities and Future Directions for Orthopedic Applications

The successful clinical application of bone tissue engineering requires customized implants based on the receiver’s bone anatomy and defect characteristics. Three-dimensional (3D) printing in small animal orthopedics has recently emerged as a valuable approach in fabricating individualized implants for receiver-specific needs. In veterinary medicine, because of the wide range of dimensions and anatomical variances, receiver-specific diagnosis and therapy are even more critical. The ability to generate 3D anatomical models and customize orthopedic instruments, implants, and scaffolds are advantages of 3D printing in small animal orthopedics. Furthermore, this technology provides veterinary medicine with a powerful tool that improves performance, precision, and cost-effectiveness. Nonetheless, the individualized 3D-printed implants have benefited several complex orthopedic procedures in small animals, including joint replacement surgeries, critical size bone defects, tibial tuberosity advancement, patellar groove replacement, limb-sparing surgeries, and other complex orthopedic procedures. The main purpose of this review is to discuss the application of 3D printing in small animal orthopedics based on already published papers as well as the techniques and materials used to fabricate 3D-printed objects. Finally, the advantages, current limitations, and future directions of 3D printing in small animal orthopedics have been addressed.     

Host Restriction Factors Modulating HIV Latency and Replication in Macrophages

In addition to CD4⁺ T lymphocytes, myeloid cells and, particularly, differentiated macrophages are targets of human immunodeficiency virus type-1 (HIV-1) infection via the interaction of gp120Env with CD4 and CCR5 or CXCR4. Both T cells and macrophages support virus replication, although with substantial differences. In contrast to activated CD4⁺ T lymphocytes, HIV-1 replication in macrophages occurs in nondividing cells and it is characterized by the virtual absence of cytopathicity both in vitro and in vivo. These general features should be considered in evaluating the role of cell-associated restriction factors aiming at preventing or curtailing virus replication in macrophages and T cells, particularly in the context of designing strategies to tackle the viral reservoir in infected individuals receiving combination antiretroviral therapy. In this regard, we will here also discuss a model of reversible HIV-1 latency in primary human macrophages and the role of host factors determining the restriction or reactivation of virus replication in these cells.     

Malignant Transformation of Giant Cell Tumour of Bone: A Review of Literature and the Experience of a Referral Centre

Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1–9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.     

Toward the discovery of novel anti-HIV drugs. Second-generation inhibitors of the cellular ATPase DDX3 with improved anti-HIV activity: synthesis, structure-activity relationship analysis, cytotoxicity studies, and target validation

A hit optimization protocol applied to the first nonnucleoside inhibitor of the ATPase activity of human DEAD-box RNA helicase DDX3 led to the design and synthesis of second-generation rhodanine derivatives with better inhibitory activity toward cellular DDX3 and HIV-1 replication. Additional DDX3 inhibitors were identified among triazine compounds. Biological data were rationalized in terms of structure-activity relationships and docking simulations. Antiviral activity and cytotoxicity of selected DDX3 inhibitors are reported and discussed. A thorough analysis confirmed human DDX3 as a valid anti-HIV target. The compounds described herein represent a significant advance in the pursuit of novel drugs that target HIV-1 host cofactors.     

Urolithin as a converging scaffold linking ellagic acid and coumarin analogues: design of potent protein kinase CK2 inhibitors

Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase; its abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other relevant diseases. Previously, using different in silico screening approaches, two potent and selective CK2 inhibitors were identified by our group: ellagic acid, a naturally occurring tannic acid derivative (K(i)=20 nM) and 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC, K(i)=60 nM). Comparing the crystallographic binding modes of both ellagic acid and DBC, an X-ray structure-driven merging approach was taken to design novel CK2 inhibitors with improved target affinity. A urolithin moiety is proposed as a possible bridging scaffold between the two known CK2 inhibitors, ellagic acid and DBC. Optimization of urolithin A as the bridging moiety led to the identification of 4-bromo-3,8-dihydroxy-benzo[c]chromen-6-one as a novel, potent and selective CK2 inhibitor, which shows a K(i) value of 7 nM against the protein kinase, representing a significant improvement in affinity for the target compared with the two parent fragments.