Dispirooxindole-β-Lactams: Synthesis via Staudinger Ketene-Imine Cycloaddition and Biological Evaluation

In this work, we present the first synthesis of dispirooxindole-β-lactams employing optimized methodology of one-pot Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with β-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against E. coli strain LPTD.     

A Novel Morphological Parameter Predicting Fibrotic Evolution in Myeloproliferative Neoplasms: New Evidence and Molecular Insights

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) represent a group of hematological disorders that are traditionally considered as indistinct slow progressing conditions; still, a subset of cases shows a rapid evolution towards myelofibrotic bone marrow failure. Specific abnormalities in the megakaryocyte lineage seem to play a central role in this evolution, especially in the bone marrow fibrosis but also in the induction of myeloproliferation. In this review, we analyze the current knowledge of prognostic factors of MPNs related to their evolution to myelofibrotic bone marrow failure. Moreover, we focused the role of the megakaryocytic lineage in the various stages of MPNs, with updated examples of MPNs in vitro and in vivo models and new therapeutic implications.     

Novel Models of Crohn’s Disease Pathogenesis Associated with the Occurrence of Mitochondrial Dysfunction in Intestinal Cells

Crohn’s disease remains one of the challenging problems of modern medicine, and the development of new and effective and safer treatments against it is a dynamic field of research. To make such developments possible, it is important to understand the pathologic processes underlying the onset and progression of Crohn’s disease at the molecular and cellular levels. During the recent years, the involvement of mitochondrial dysfunction and associated chronic inflammation in these processes became evident. In this review, we discuss the published works on pathogenetic models of Crohn’s disease. These models make studying the role of mitochondrial dysfunction in the disease pathogenesis possible and advances the development of novel therapies.     

Chelating Polymers for Targeted Decontamination of Actinides: Application of PEI-MP to Hydroxyapatite-Th(IV)

In case of an incident in the nuclear industry or an act of war or terrorism, the dissemination of plutonium could contaminate the environment and, hence, humans. Human contamination mainly occurs via inhalation and/or wounding (and, less likely, ingestion). In such cases, plutonium, if soluble, reaches circulation, whereas the poorly soluble fraction (such as small colloids) is trapped in alveolar macrophages or remains at the site of wounding. Once in the blood, the plutonium is delivered to the liver and/or to the bone, particularly into its mineral part, mostly composed of hydroxyapatite. Countermeasures against plutonium exist and consist of intravenous injections or inhalation of diethylenetetraminepentaacetate salts. Their effectiveness is, however, mainly confined to the circulating soluble forms of plutonium. Furthermore, the short bioavailability of diethylenetetraminepentaacetate results in its rapid elimination. To overcome these limitations and to provide a complementary approach to this common therapy, we developed polymeric analogs to indirectly target the problematic retention sites. We present herein a first study regarding the decontamination abilities of polyethyleneimine methylcarboxylate (structural diethylenetetraminepentaacetate polymer analog) and polyethyleneimine methylphosphonate (phosphonate polymeric analog) directed against Th(IV), used here as a Pu(IV) surrogate, which was incorporated into hydroxyapatite used as a bone model. Our results suggest that polyethylenimine methylphosphonate could be a good candidate for powerful bone decontamination action.     

A neural network based intelligent system for tile prefetching in web map services

Web mapping has become a popular way of distributing interactive digital maps over the internet. Instead of dynamically generating map images on the fly, those can be pre-generated and served from a server-side cache for faster retrieval. However, these caches can grow unmanageably in size when the cartography covers mid to large areas for multiple rendering scales. This forces modest organizations to use partial caches containing just a subset of the total tiles, and makes their services less attractive than other mapping services like Google Maps or Microsoft Bing Maps. This work proposes a neural-network-based intelligent system that predicts which areas are likely to be requested in the future from a catalog of geographic features and a short history of past requests. These priority regions can be used by a tile prefetching policy to achieve an optimal population of the cache. Neural networks are trained and validated using supervised learning with real data-sets from a public nation-wide web map service. Trace-driven simulations demonstrate that accurate long-term predictions, up to 90% in terms of cache-hit ratio, can be obtained with the proposed model by prefetching a low fraction, only the 20% of the total tiles, and with a short training period.     

Mechanical squeezing of an elastomeric nanochannel device: numerical simulations and ionic current characterization

Peculiar transport phenomena appear at nanoscale, since surface effects strongly affect the behaviour of fluids. Electrostatic and steric interactions, capillary forces and entropic effects play a key role in the behaviour of fluids and biomolecules. Since these effects strongly depend on the size of the nanofluidic system, a careful characterization of the fluidic environment is necessary. Moreover, the possibility to dynamically modulate the size of nanochannels is very appealing in the field of biomolecule manipulation. Recently, we have developed a lab-on-chip made of poly(dimethylsiloxane) (PDMS). This polymeric device is based on a tuneable nanochannel able to dynamically change its dimension in order to fit the application of interest. In fact, a mechanical compression applied on the top of the elastomeric device squeezes the nanochannel, reducing the channel cross section and allowing a dynamical optimization of the nanostructures. In this paper, this squeezing process is fully characterized both numerically and experimentally. This analysis provides information on the reduction of the nanochannel dimensions induced by compression as a function of the work of adhesion and of the stiffness of the materials composing the device. Moreover, calculations demonstrate the possibility to predict the change of the nanochannel size and shape induced by the compression. The possibility to dynamically tune the channel size opens up new opportunities in biomolecular sensing or sieving and in the study of new hydrodynamics effects.     

Fix-and-Relax-Coordination for a multi-period location–allocation problem under uncertainty

A multi-period discrete facility location problem is introduced for a risk neutral strategy with uncertainty in the costs and some of the requirements along the planning horizon. A compact 0–1 formulation for the Deterministic Equivalent Model of the problem under two alternative strategies for the location decisions is presented. Furthermore, a new algorithmic matheuristic, Fix-and-Relax-Coordination, is introduced. This solution scheme is based on a specialization of the Branch-and-Fix Coordination methodology, which exploits the Nonanticipativity Constraints and uses the Twin Node Family concept. The results of an extensive computational experience allow to compare the alternative modeling strategies and assess the effectiveness of the proposed approach versus the plain use of a state-of-the-art MIP solver.     

Three-dimensional optical data storage through multi-photon confocal microscopy and imaging

Three dimensional optical data storage is one of the most promising tools to respond to the always growing demand for high data storage capacity. Here, we focused a femtosecond laser source by means of a confocal microscope onto different transparent recording media. The purpose of the study is to probe the capability of the system to independently address different data layers within the storage medium achieving thus three dimensional data storage. We demonstrated the possibility to write superposed independent layers of data due to either multiphoton excitation or to local optical breakdown and the performances observed in the different types of media used are compared.     

Mixed Messages about Mixed Tenure: Do Reviews Tell the Real Story?

Mixed tenure is the predominant development and regeneration strategy and is a key component of UK housing and urban policy. It is purported to provide wide-ranging social, environmental and economic benefits to residents. While there is a large literature on mixed tenure, policy makers are likely to rely on reviews and summaries of the evidence rather than primary studies. But can they rely on such reviews? Using systematic review methods this paper critically appraises recent reviews for the evidence that mixed tenure policies and strategies have achieved any of these expected benefits. Of the six UK reviews of primary studies, most drew on less than half the available primary studies, none provided a critical appraisal of individual studies and made no comment on conflicting evidence between and within studies. While the reviews gave indications of the deficiencies of the evidence base, rather than focus on the implications of these deficiencies, four of the six reviews emphasised the positive effects of tenure mix.