Infrared absorption from Charge Density Waves in magnetic manganites

The infrared absorption of charge density waves coupled to a magnetic background is first observed in two manganites La{1-x}Ca{x}MnO{3} with x = 0.5 and x = 0.67. In both cases a BCS-like gap 2 Delta (T), which for x=0.5 follows the hysteretic ferro-antiferromagnetic transition, fully opens at a finite T{0} < T{Neel}, with 2 Delta(T{0})/kT{c} close to 5. These results may also explain the unusual coexistence of charge ordering and ferromagnetism in La{0.5}Ca{0.5}MnO{3}.Comment: File revtex + 3 figs. in epsf. To appear on Phys. Rev. Let

Peaceful coexistence: agile developer perspectives on software architecture.

This study aims to explore the relationship between agility and architecture by surveying 72 software developers at IBM. Results suggest that software architecture and agility are not like oil and water. In particular, Agile developers perceived architectures as important and supportive (rather than in contrast or neutral) to agile values. This kind of positive perception of software architectural principles and practice bodes well for future efforts to integrate agile and architecture practices

Systems Level Approach Reveals the Correlation of Endoderm Differentiation of Mouse Embryonic Stem Cells with Specific Microstructural Cues of Fibrin Gels.

Stem cells receive numerous cues from their associated substrate that help to govern their behaviour. However, identification of influential substrate characteristics poses difficulties because of their complex nature. In this study, we developed an integrated experimental and systems level modelling approach to investigate and identify specific substrate features influencing differentiation of mouse embryonic stem cells (mESCs) on a model fibrous substrate, fibrin. We synthesized a range of fibrin gels by varying fibrinogen and thrombin concentrations, which led to a range of substrate stiffness and microstructure. mESCs were cultured on each of these gels, and characterization of the differentiated cells revealed a strong influence of substrate modulation on gene expression patterning. To identify specific substrate features influencing differentiation, the substrate microstructure was quantified by image analysis and correlated with stem cell gene expression patterns using a statistical model. Significant correlations were observed between differentiation and microstructure features, specifically fibre alignment. Furthermore, this relationship occurred in a lineage-specific manner towards endoderm. This systems level approach allows for identification of specific substrate features from a complex material which are influential to cellular behaviour. Such analysis may be effective in guiding the design of scaffolds with specific properties for tissue engineering applications

Stem-like and highly invasive prostate cancer cells expressing CD44v8-10 marker originate from CD44-negative cells

In human prostate cancer (PCa), the neuroendocrine cells, expressing the prostate cancer stem cell (CSC) marker CD44, may be resistant to androgen ablation and promote tumor recurrence. During the study of heterogeneity of the highly aggressive neuroendocrine PCa cell lines PC3 and DU-145, we isolated and expanded in vitro a minor subpopulation of very small cells lacking CD44 (CD44neg). Unexpectedly, these sorted CD44neg cells rapidly and spontaneously converted to a stable CD44high phenotype specifically expressing the CD44v8-10 isoform which the sorted CD44high subpopulation failed to express. Surprisingly and potentially interesting, in these cells expression of CD44v8-10 was found to be induced in stem cell medium. CD44 variant isoforms are known to be more expressed in CSC and metastatic cells than CD44 standard isoform. In agreement, functional analysis of the two sorted and cultured subpopulations has shown that the CD44v8-10pos PC3 cells, resulting from the conversion of the CD44neg subpopulation, were more invasive in vitro and had a higher clonogenic potential than the sorted CD44high cells, in that they produced mainly holoclones, known to be enriched in stem-like cells. Of interest, the CD44v8-10 is more expressed in human PCa biopsies than in normal gland. The discovery of CD44v8-10pos cells with stem-like and invasive features, derived from a minoritarian CD44neg cell population in PCa, alerts on the high plasticity of stem-like markers and urges for prudency on the approaches to targeting the putative CSC

L-DOPA preloading increases the uptake of borophenylalanine in C6 glioma rat model: a new strategy to improve BNCT efficacy.

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10B(n,a)7Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of 10B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for 10B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first per- formed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectros- copy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All an- imals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malig- nant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms

Osteoporosis in adult with Marfan syndrome: casuality or causality?

Nearly 100 years ago, Antoine Marfan first described a recurrent systemic disorder of connective tissue characterized by overgrowth of the long bones (1). It took an additional 50 years before ocular and cardiovascular manifestations were associated with this disorder, now termed Marfan syndrome (MFS). MFS is an inherited connective tissue disorder transmitted as an autosomal dominant trait. This relatively common genetic condition affects approximately 2 to 3 per 10,000 individuals, without a particular gender, racial, geographic, or ethnic predilection (2). The disorder results from mutations in the fibrillin-1 (FBN1) gene located on chromosome 15q21.1(3). Approximately 15% of cases occur in the absence of a family history, representing new mutations; infact to date, over 550 mutations have been identified in patients with MFS and related connective tissue diseases. However, about a half of MFS cases do not possess mutations in the FBN1 gene..

Sjogren's syndrome: apoptosis by anti-SSA and anti-SSB antibodies

The pathogenesis of the Sjogren's Syndrome (SjS) has not yet been completely defined. However, the cell-mediated immunity plays an important role and the apoptosis of the ductal and acinar epithelial cells is responsible of the glandular tissue damage, through the cytotoxic T-cells, particularly of the CD4+ subpopulation, by the release of proteases (such as perforin and granzyme B) and by the interaction of the Fas Ligand (FasL; CD95L) of the T-lymphocytes, with the Fas (Apo-1; CD95) of the epithelial cells. The apoptotic death of the epithelial cells is the autocrine Fas/FasL interaction also. The anti-SSA and anti-SSB antibodies are the immunological markers of the Sjogren's syndrome, but it is not yet understood if they have pathogenetic implications...

Minute-timescale free-energy calculations reveal a pseudo-active state in the adenosine A2A receptor activation mechanism

G protein-coupled receptors (GPCRs) are membrane proteins targeted by over one-third of marketed drugs. Understanding their activation mechanism is essential for precise regulation of drug pharmacological response. In this work, we elucidate the conformational landscape of the adenosine A2A receptor (A2AR) activation mechanism in its basal apo form and under different ligand-bound conditions through minute-timescale free-energy calculations. We identified a pseudo-active state (pAs) of the A2AR apo form, stabilized by specific “microswitch” residues, including a salt bridge established between the conserved residues R5.66 and E6.30. The pAs enables A2AR to couple with Gs protein upon rearrangement of the intracellular end of transmembrane helix 6, providing unprecedented structural insights into receptor function and signaling dynamics. Our simulation protocol is versatile and can be adapted to study the activation of any GPCRs, potentially making it a valuable tool for drug design and “biased signaling” studies

Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells

Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy. © 2015 Macmillan Publishers Limited. All rights reserved

Selective leaching of precious metals from electrical and electronic equipment through hydrometallurgical methods

The rapid human evolution has improved the quality of our lives through the use of technology. This not only resulted in increased raw materials extraction but also in the production of a worrying amount of electronic wastes. Indeed, in 2019 worldwide production of Electronic and Electric Equipment Waste (WEEE) was worth 50 million tons, causing several disadvantages such as the reduced space in landfills and massive shipping to countries with less restrictive regulations. On the other side, the billionaire electrical devices market is causing a significant increase in Precious Metals (PM) demand. Nowadays, the economic importance of PMs is as high as their supply risk. The answer to this problem consists of finding selective methods to extract and raffinate precious metals from disposed WEEE. On average, WEEEs contain around 30 % of plastics, 30 % ceramics, and 40 % metals; among these only around 0.1 % is characterized by PMs, such as gold, silver, rhodium, platinum, and palladium. The separation of PMs from other non-precious components is generally obtained using pyrometallurgy, which consists of fusing the wastes at temperatures up to 1500 ÷ 1700 °C. However, this method produces toxic gaseous byproducts and implies high energy costs. A possible alternative is given by hydrometallurgical processes, consisting of leaching the WEEE with solutions containing acids and oxidants at temperatures lower than 100°C. One of the main issues of the hydrometallurgical process is to leach copper and other non-precious base-metals selectively while keeping PMs in the solid-state. In this work, we report preliminary results of equilibrium and kinetic leaching tests in a well-stirred batch reactor, aimed at the optimization of the main operating parameters of a hydrometallurgical process for selective leaching of copper and other base-metals from Wasted Printed Circuit Boards (WPCBs). In particular, experiments have been carried out at different HCl and NaCl concentrations of the leaching solutions, exploring also the effect of temperature variation (20, 50, and 70 °C)