Absolute copy number and relative change in determinations of human immunodeficiency virus type 1 RNA in plasma: effect of an external standard on kit comparisons

Use of a common set of human immunodeficiency virus type 1 (HIV-1) RNA standards eliminated differences among absolute HIV-1 RNA copy number estimates made with three commercially available assays. The relative changes in the viral RNA levels determined by the commercial assays were similar and were unaffected by the use of a common set of standards.     

Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung tumors

Neural cell adhesion molecules (NCAM) represent specific markers of neuroendocrine (NE) differentiation in lung cancer. Because the polysialic acid form (NCAM-PSA) has reduced adhesion properties, we hypothesized that NCAM-PSA expression could favor metastatic spread. Immunostaining of NCAM and NCAM-PSA were therefore compared in 120 NE lung tumors, including 17 typical carcinoids, 3 atypical carcinoids, 30 large cell NE carcinomas and 70 small cell lung carcinomas, as compared with 25 adenocarcinomas and 25 squamous cell carcinomas. Neural cell adhesion molecules were negative in adenocarcinomas and squamous cell carcinomas but were constantly expressed in all NE tumors from typical carcinoids to small cell lung carcinomas. NCAM-PSA expression was significantly more frequent in high-grade tumors, with 24 of 30 positive cases in large cell NE carcinomas and 65 of 70 positive cases in small cell lung carcinoma, than in carcinoids with 10 of 17 and 2 of 3 positive cases in typical carcinoids and atypical carcinoids, respectively. The neural cell adhesion molecule-polysialic acid form scores of staining were significantly higher in high-grade as compared with low-grade tumors (p = 0.002), and were correlated with nodal spread (p = 0.04) and metastasis (p = 0.016) across histologic classes but not in individual tumor type. We conclude that NCAM-PSA connotes poor differentiation and aggressive clinical behavior in the spectrum of NE lung tumors, but cannot be regarded as a prognostic factor in individual tumor classes.     

Analysing the cognitive effectiveness of the WebML visual notation

WebML is a domain-specific language used to design complex data-intensive Web applications at a conceptual level. As WebML was devised to support design tasks, the need to define a visual notation for the language was identified from the very beginning. Each WebML element is consequently associated with a separate graphical symbol which was mainly defined with the idea of providing simple and expressive modelling artefacts rather than by adopting a rigorous scientific approach. As a result, the graphical models defined with WebML may sometimes prevent proper communication from taking place between the various stakeholders. In fact, this is a common issue for most of the existing model-based proposals that have emerged during the last few years under the umbrella of model-driven engineering. In order to illustrate this issue and foster in using a scientific basis to design, evaluate, improve and compare visual notations, this paper analyses WebML according to a set of solid principles, based on the theoretical and empirical evidence concerning the cognitive effectiveness of visual notations. As a result, we have identified a set of possible improvements, some of which have been verified by an empirical study. Furthermore, a number of findings, experiences and lessons learnt on the assessment of visual notations are presented.     

Colocalization and Interaction Study of Neuronal JNK3, JIP1, and β-Arrestin2 Together with PSD95

c-Jun N-terminal kinases (JNKs) are stress-activated serine/threonine protein kinases belonging to the mitogen-activated protein kinase (MAPK) family. Among them, JNK3 is selectively expressed in the central nervous system, cardiac smooth muscle, and testis. In addition, it is the most responsive JNK isoform to stress stimuli in the brain, and it is involved in synaptic dysfunction, an essential step in neurodegenerative processes. JNK3 pathway is organized in a cascade of amplification in which signal transduction occurs by stepwise, highly controlled phosphorylation. Since different MAPKs share common upstream activators, pathway specificity is guaranteed by scaffold proteins such as JIP1 and β-arrestin2. To better elucidate the physiological mechanisms regulating JNK3 in neurons, and how these interactions may be involved in synaptic (dys)function, we used (i) super-resolution microscopy to demonstrate the colocalization among JNK3–PSD95–JIP1 and JNK3–PSD95–β-arrestin2 in cultured hippocampal neurons, and (ii) co-immunoprecipitation techniques to show that the two scaffold proteins and JNK3 can be found interacting together with PSD95. The protein-protein interactions that govern the formation of these two complexes, JNK3–PSD95–JIP1 and JNK3–PSD95–β-arrestin2, may be used as targets to interfere with their downstream synaptic events.     

Scoping Review on Platelets and Tumor Angiogenesis: Do We Need More Evidence or Better Analysis?

Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated rich in angiogenic factors in their granules to actively participate in the hemostatic process by megakaryocytes and further enriched in angiogenic factors by all components of the tumor microenvironment to control the angiogenic process because of their preferential relationship with the endothelial component of vessels. In recent decades, the literature has reported a great deal of evidence on the role of platelets in tumor angiogenesis; however, it is unclear whether the number or mean volume of platelets and/or their content and localization in TME may have clinical relevance in the choice and management of therapy for the cancer patient. In this scoping review, we collected and critically reviewed the scientific evidence supporting a close relationship between platelets, cancer, and angiogenesis. The aim of this work was to define the landscape of platelet-activated angiogenesis in cancer progression and analyze what and how much evidence is present in the last 20 years in the literature at both the preclinical and clinical levels, to answer whether platelets could be a useful determinant for analyzing tumor angiogenesis. In conclusion, this scoping review indicates that there is much evidence, both preclinical and clinical, but in the preclinical context, studies demonstrate the direct involvement of platelets in tumor angiogenesis; in the clinical context the evidence is indirect, though strong, and the indication of how and to what extent platelet content contributes to tumor angiogenesis is lacking. So, do we need more evidence or better analysis? More molecular and quali-quantitative data is needed to translate the results obtained in preclinical studies into the clinical setting. This information about platelets, if correlated with tumor type and its biology, including tumor vasculature, type of angiogenesis, and patient characteristics (age, sex, comorbidities, drug treatments for chronic diseases) could be an important pa- rameter for correlating platelet biology to angiogenesis, for personalizing cancer therapy, and for clinical prognosis.     

Erythro–Magneto–HA–Virosome: A Bio-Inspired Drug Delivery System for Active Targeting of Drugs in the Lungs

Over the past few decades, finding more efficient and selective administration routes has gained significant attention due to its crucial role in the bioavailability, absorption rate and pharmacokinetics of therapeutic substances. The pulmonary delivery of drugs has become an attractive target of scientific and biomedical interest in the health care research area, as the lung, thanks to its high permeability and large absorptive surface area and good blood supply, is capable of absorbing pharmaceuticals either for local deposition or for systemic delivery. Nevertheless, the pulmonary drug delivery is relatively complex, and strategies to mitigate the effects of mechanical, chemical and immunological barriers are required. Herein, engineered erythrocytes, the Erythro–Magneto–Hemagglutinin (HA)–virosomes (EMHVs), are used as a novel strategy for efficiently delivering drugs to the lungs. EMHV bio-based carriers exploit the physical properties of magnetic nanoparticles to achieve effective targeting after their intravenous injection thanks to an external magnetic field. In addition, the presence of hemagglutinin fusion proteins on EMHVs’ membrane allows the DDS to anchor and fuse with the target tissue and locally release the therapeutic compound. Our results on the biomechanical and biophysical properties of EMHVs, such as the membrane robustness and deformability and the high magnetic susceptibility, as well as their in vivo biodistribution, highlight that this bio-inspired DDS is a promising platform for the controlled and lung-targeting delivery of drugs, and represents a valuable alternative to inhalation therapy to fulfill unmet clinical needs.     

Octadecyl-modified silica supports for metallocene catalyst applied in ethylene polymerization

Chemical modification of silica-based supports is an alternative route for modulating the active sites of metallocene catalysts, presenting the potential to obtain polyethylenes with improved properties. Therefore, this work investigates the effect of octadecylsilane content in silica support on the behavior of resulting supported metallocene catalysts on ethylene polymerization. For this propose, a series of octadecyl-modified silicas whit different amounts of octadecyl (ODS) groups were synthesized by a modified Stöber sol–gel method and then applied as supports for a metallocene catalyst. The supported metallocene catalysts were evaluated in ethylene polymerization and ethylene/1-hexene copolymerization reactions. Besides, studies of the growth kinetics of polyethylene particles in a gas phase reactor were performed using videomicroscopy. The octadecylsilane content in the supports was in the range of 0.2 to 1.4 mmol g⁻¹. DRIFTS and ¹³C CP/MAS NMR results showed a predominance of an all-trans octadecyl chain conformation. SEM images showed spherical particle morphology for silicas having octadecylsilane content up to 0.6 mmol g⁻¹. The supported catalysts presented activity in ethylene polymerization in the range of 1100–1900 kg PE molZr⁻¹ h⁻¹ bar⁻¹. The surface polarity of the catalyst influenced the molar mass of the resulting polyethylene. The increase of the ODS content on the silica surface led to a supported catalyst with slower kinetic behavior in the gas phase, which might be attributed to the diffusive effects of the octadecyl layer on the catalyst surface.