Distillation of Quantum Steering.

We show-both theoretically and experimentally-that Einstein-Podolsky-Rosen steering can be distilled. We present a distillation protocol that outputs a perfectly correlated system-the singlet assemblage-in the asymptotic infinite-copy limit, even for inputs that are arbitrarily close to being unsteerable. As figures of merit for the protocol's performance, we introduce the assemblage fidelity and the singlet-assemblage fraction. These are potentially interesting quantities on their own beyond the current scope. Remarkably, the protocol works well also in the nonasymptotic regime of few copies, in the sense of increasing the singlet-assemblage fraction. We demonstrate the efficacy of the protocol using a hyperentangled photon pair encoding two copies of a two-qubit state. This represents to our knowledge the first observation of deterministic steering concentration. Our findings are not only fundamentally important but may also be useful for semi-device-independent protocols in noisy quantum networks.

Quantum Steering Beyond Instrumental Causal Networks.

We theoretically predict, and experimentally verify with entangled photons, that outcome communication is not enough for hidden-state models to reproduce quantum steering. Hidden-state models with outcome communication correspond, in turn, to the well-known instrumental processes of causal inference but in the one-sided device-independent scenario of one black-box measurement device and one well-characterized quantum apparatus. We introduce one-sided device-independent instrumental inequalities to test against these models, with the appealing feature of detecting entanglement even when communication of the black box's measurement outcome is allowed. We find that, remarkably, these inequalities can also be violated solely with steering, i.e., without outcome communication. In fact, an efficiently computable formal quantifier-the robustness of noninstrumentality-naturally arises, and we prove that steering alone is enough to maximize it. Our findings imply that quantum theory admits a stronger form of steering than known until now, with fundamental as well as practical potential implications.

A three-dimensional view of structural changes caused by deactivation of fluid catalytic cracking catalysts.

Since its commercial introduction three-quarters of a century ago, fluid catalytic cracking has been one of the most important conversion processes in the petroleum industry. In this process, porous composites composed of zeolite and clay crack the heavy fractions in crude oil into transportation fuel and petrochemical feedstocks. Yet, over time the catalytic activity of these composite particles decreases. Here, we report on ptychographic tomography, diffraction, and fluorescence tomography, as well as electron microscopy measurements, which elucidate the structural changes that lead to catalyst deactivation. In combination, these measurements reveal zeolite amorphization and distinct structural changes on the particle exterior as the driving forces behind catalyst deactivation. Amorphization of zeolites, in particular, close to the particle exterior, results in a reduction of catalytic capacity. A concretion of the outermost particle layer into a dense amorphous silica-alumina shell further reduces the mass transport to the active sites within the composite.Catalyst deactivation in fluid catalytic cracking processes is unavoidably associated with structural changes. Here, the authors visualize the deactivation of zeolite catalysts by ptychography and other imaging techniques, showing pronounced amorphization of the outer layer of the catalyst particles.

Effects of rapid maxillary expansion and mandibular advancement on upper airways in Marfan's syndrome children: a home sleep study and cephalometric evaluation.

PURPOSE: Evaluation of the effects of rapid maxillary expansion and mandibular advancement using Propulsor Universal Light appliance on the upper airways in Marfan's syndrome children through home sleep studies, Epworth Sleepiness Scale questionnaire, and cephalometric analysis of the upper airways on lateral radiographs. METHODS: The study sample consisted of 30 children with Marfan's syndrome, and the control group consisted of 30 untreated and matched children. For Marfan subjects, data were taken at different time points compared to treatment: at T0 (before treatment), T1 (after rapid maxillary expansion), and T2 (after mandibular advancement). For control subjects, data were taken at similar intervals, at three follow-up visits: at T0 (as a starting screening tool), T1 (after approximately 2 years), and T2 (in proximity of the peak skeletal growth). RESULTS: Apnea-hypopnea and oxygen desaturations were significantly higher in the study group at T0 and T1 compared with control children. At T2, the values were not significant (p value 0.442 for both apnea-hypopnea index (AHI) and oxygen desaturation index (ODI)). Horizontal airway dimensions were significantly reduced, and vertical airway values were significantly increased in Marfan's syndrome at T0 and T1 but not at T2 (p values at T2: 0.071 for Phw1-Psp, 0.106 for Phw1-Psp', 0.101 for Phw2-Tb, 0.559 for UAL in male and 0.560 for UAL in female). CONCLUSIONS: Early rapid maxillary expansion and mandibular advancement using Propulsor Universal Light appliance significantly improved airway patency of Marfan's syndrome children and are strongly encouraged as a routine treatment for both correction of class II malocclusions and prevention of obstructive sleep apnea.

Determination of 63Ni and 59Ni in spent ion-exchange resin and activated charcoal from the IEA-R1 nuclear research reactor.

A radiochemical method has been adapted to determine (59)Ni and (63)Ni in samples of radioactive wastes from the water cleanup system of the IEA-R1 nuclear research reactor. The process includes extraction chromatographic resin with dimethylglyoxime (DMG) as a functional group. Activity concentrations of (59)Ni and (63)Ni were measured, respectively, by X-ray spectrometry and liquid scintillation counting, whereas the chemical yield was determined by ICP-OES. The average ratio of measured activity concentrations of (63)Ni and (59)Ni agree well with theory.

Quantum speed limit for physical processes.

The evaluation of the minimal evolution time between two distinguishable states of a system is important for assessing the maximal speed of quantum computers and communication channels. Lower bounds for this minimal time have been proposed for unitary dynamics. Here we show that it is possible to extend this concept to nonunitary processes, using an attainable lower bound that is connected to the quantum Fisher information for time estimation. This result is used to delimit the minimal evolution time for typical noisy channels.

Anoikis: an emerging hallmark in health and diseases.

Anoikis is a programmed cell death occurring upon cell detachment from the correct extracellular matrix, thus disrupting integrin ligation. It is a critical mechanism in preventing dysplastic cell growth or attachment to an inappropriate matrix. Anoikis prevents detached epithelial cells from colonizing elsewhere and is thus essential for tissue homeostasis and development. As anchorage-independent growth and epithelial-mesenchymal transition, two features associated with anoikis resistance, are crucial steps during tumour progression and metastatic spreading of cancer cells, anoikis deregulation has now evoked particular attention from the scientific community. The aim of this review is to analyse the molecular mechanisms governing both anoikis and anoikis resistance, focusing on their regulation in physiological processes, as well as in several diseases, including metastatic cancers, cardiovascular diseases and diabetes.

Accreditation and training on internal dosimetry in a laboratory network in Brazil: an increasing demand.

In recent years, Brazilian Nuclear Programme has been reviewed and updated by government authorities in face of the demand for energy supply and its associated environmental constraints. The immediate impact of new national programmes and projects in nuclear field is the increase in the number of exposed personnel and the consequent need for reliable dosimetry services in the country. Several Technical Documents related to internal dosimetry have been released by the International Atomic Energy Agency and International Commission on Radiological Protection. However, standard bioassay procedures and methodologies for bioassay data interpretation are still under discussion and, in some cases, both in routine and emergency internal monitoring, procedures can vary from one laboratory to another and responses may differ markedly among Dosimetry Laboratories. Thus, it may be difficult to interpret and use bioassay data generated from different laboratories of a network. The main goal of this work is to implement a National Network of Laboratories aimed to provide reliable internal monitoring services in Brazil. The establishment of harmonised in vivo and in vitro radioanalytical techniques, dose assessment methods and the implementation of the ISO/IEC 17025 requirements will result in the recognition of technical competence of the network.

Redox regulation of anoikis: reactive oxygen species as essential mediators of cell survival.

Proper attachment to the extracellular matrix (ECM) is essential for cell survival. The loss of integrin-mediated cell-ECM contact results in an apoptotic process termed anoikis. However, mechanisms involved in regulation of cell survival are poorly understood and mediators responsible for anoikis have not been well characterized. Here, we demonstrate that reactive oxygen species (ROS) produced through the involvement of the small GTPase Rac-1 upon integrin engagement exert a mandatory role in transducing a pro-survival signal that ensures that cells escape from anoikis. In particular, we show that ROS are responsible for the redox-mediated activation of Src that trans-phosphorylates epidermal growth factor receptor (EGFR) in a ligand-independent manner. The redox-dependent phosphorylation of EGFR activates both extracellular signal-regulated protein kinase and Akt downstream signalling pathways, culminating in degradation of the pro-apoptotic protein Bim. Hence, our results shed new light on the mechanism granting the adhesion-dependent antiapoptotic effect, highlighting a fundamental role of ROS-mediated Src regulation in ensuring anoikis protection.

Oxidation and tyrosine phosphorylation: synergistic or antagonistic cues in protein tyrosine phosphatase.

Protein tyrosine phosphatases (PTPs) have been generally recognised as key modulators of cell proliferation, differentiation, adhesion and motility. During signalling, several PTPs undergo two posttranslational modifications that greatly affect their enzymatic activity: tyrosine phosphorylation and cysteine oxidation. Although these modifications share their reversibility depending on the intracellular environment, their effects on enzymatic activity are opposite, tyrosine phosphorylation being correlated to enzyme activation and thiol oxidation to complete inactivation. Several papers have suggested that both these modifications occur in response to the same stimuli i.e. cell proliferation induced by numerous growth factors and cytokines. Conversely, the possibility that these two regulation mechanisms act simultaneously on PTPs has not been established and very few reports investigated this dual regulation of PTPs. To underline the relevance of the question, we discuss several possibilities: (i) that tyrosine phosphorylation and cysteine oxidation of PTPs may share the same target molecules but with different kinetics; (ii) that PTP phosphorylation and oxidation may take place on different subcellular pools of the same protein and (iii) that these two modifications, although having divergent effects on enzyme activity, cooperate in the integrated and coordinated function of PTPs during receptor tyrosine kinase signalling. We believe that our perspective will open new perspectives on an ancient problem--the apparent contradiction of opposing enzymatic regulation of many PTPs--thus clarifying their role as positive or negative transducers (or both) of many extracellular stimuli.

Insulin inhibits platelet-derived growth factor-induced cell proliferation.

Cellular behavior can be considered to be the result of a very complex spatial and temporal integration of intracellular and extracellular signals. These signals arise from serum-soluble factors as well as from cell-substrate or cell-cell interactions. The current approach in mitogenesis studies is generally to analyze the effect of a single growth factor on serum-starved cells. In this context, a metabolic hormone such as insulin is found to be a mitogenic agent in many cellular types. In the present study, we have considered the effect of insulin stimulation in platelet-derived growth factor (PDGF)-activated NIH-3T3 and C2C12 cells. Our results show that insulin is able to inhibit strongly both NIH-3T3 and C2C12 cell growth induced by PDGF, one of the most powerful mitotic agents for these cell types. This inhibitory effect of insulin is due primarily to a premature down-regulation of the PDGF receptor. Thus, when NIH-3T3 or C2C12 cells are stimulated with both PDGF and insulin, we observe a decrease in PDGF receptor phosphorylation with respect to cells treated with PDGF alone. In particular, we find that costimulation with insulin leads to a reduced production of H2O2 with respect to cell stimulation with PDGF alone. The relative low concentration of H2O2 in PDGF/insulin-costimulated cell leads to a limited down-regulation of protein tyrosine phosphatases, and, consequently, to a reduced PDGF receptor phosphorylation efficiency. The latter is very likely to be responsible for the insulin-dependent inhibition of PDGF-receptor mitogenic signaling.

Erythrocyte Na/K-ATPase is increased in subjects with subclinical hypothyroidism.

OBJECTIVE: In erythrocytes of patients with overt hyperthyroidism, the number of ouabain-binding sites and the activity of the Na(+)/K(+)-ATPase have been demonstrated to be decreased, whereas the opposite is true in patients with overt hypothyroidism. No information has been reported on the status of the Na(+)/K(+)-ATPase in subclinically hypothyroid (Sub Hypo) patients. DESIGN: We investigated the number of ouabain-binding sites and Na(+)/K(+)-ATPase activity in erythrocytes of chronic Sub Hypo subjects. PATIENTS AND METHODS: We measured (3)H-ouabain-binding sites in erythrocytes from 15 patients with subclinical hypothyroidism, and compared with those found in 17 normal subjects (N), seven with overt hypothyroidism (Hypo) and 10 with overt hyperthyroidism (Hyper). The activity of the sodium pump was assessed by measuring ouabain-sensitive (86)Rb uptake in a subpopulation of the same groups. RESULTS: The number of ouabain-binding sites in Sub Hypo patients (252 +/- 17; mean +/- SEM) was significantly higher (P < 0.02) than in Hyper (135 +/- 12) and N (203 +/- 10) groups, whereas it was not significant different from Hypo (293 +/- 31). There was a positive correlation between the number of ouabain-binding sites and TSH concentrations (P < 0.002) when Sub Hypo and N groups were considered together. There was a negative correlation between the number of ouabain-binding sites and free thyroxine (FT4; P < 0.0001) and free triiodothyronine (FT3) concentrations (P < 0.001) when all subjects were considered. Ouabain-sensitive (86)Rb uptake (picomoles (86)Rb/h 10(6) cells) in Sub Hypo was significantly higher (4.2 +/- 0.5) when compared with N (2.5 +/- 0.2, P < 0.01) and Hyper (2.5 +/- 0.5, P < 0.02). CONCLUSIONS: Erythrocytes of subclinically hypothyroid patients show a significant increase in the number of ouabain-binding sites and in ouabain-sensitive (86)Rb uptake. The state of erythrocyte Na(+)/K(+)-ATPase may therefore represent a biochemical marker of subclinical hypothyroidism.

Down-regulation of platelet-derived growth factor receptor signaling during myogenesis.

Cell differentiation is often associated with a block in the cell cycle. Growth factor signaling has been reported to be impaired in differentiated cells, due to the withdrawal of growth factors or to transcriptional down-regulation of their receptors. Our proposal is that the down regulation of growth factor signaling may be achieved through an alternative pathway: the decrease of growth factor receptor activation and the ensuing inhibition of intracellular pathways leading the cell to division. Here we report that platelet-derived growth factor receptor (PDGFr) signaling is down-regulated during muscle differentiation, although its expression level remains unchanged. PDGFr signaling inhibition is achieved through a decrease in the receptor tyrosine phosphorylation level, in particular of Tyr716, Tyr751, Tyr857 and Tyr1021, leading to down-regulation of intracellular signaling pathways. Furthermore, during myogenesis, the expression level of several phosphotyrosine phosphatases (PTPs) increases and most of them shift toward the reduced/activated state. We propose a causal link between the down-regulation of PDGFr tyrosine phosphorylation and the increases in PTP specific activity during myogenesis.

First stereocontrolled synthesis of (S)-cleonin and related cyclopropyl-substituted amino acids.

[reaction: see text]. Enantiomerically pure (S)-cleonin, a key component of the antitumor antibiotic cleomycin, was prepared starting from (R)-serine. The Kulinkovich cyclopropanation of the methyl ester of N-Cbz serine acetonide gave the hydroxycyclopropyl moiety. The amino alcohol region was further oxidized to amino acid. The Kulinkovich cyclopropanation allowed also the preparation of other non-natural substituted cyclopropylglycines.

Low molecular weight protein-tyrosine phosphatase is involved in growth inhibition during cell differentiation.

Low molecular weight protein-tyrosine phosphatase (LMW-PTP) is an enzyme involved in mitogenic signaling and cytoskeletal rearrangement after platelet-derived growth factor (PDGF) stimulation. Recently, we demonstrated that LMW-PTP is regulated by a redox mechanism involving the two cysteine residues of the catalytic site, which turn reversibly from reduced to oxidized state after PDGF stimulation. Since recent findings showed a decrease of intracellular reactive oxygen species in contact inhibited cells and a lower tyrosine phosphorylation level in dense cultures in comparison to sparse ones, we studied if the level of endogenous LMW-PTP is regulated by growth inhibition conditions, such as cell confluence and differentiation. Results show that both cell confluence and cell differentiation up-regulate LMW-PTP expression in C2C12 and PC12 cells. We demonstrate that during myogenesis LMW-PTP is regulated at translational level and that the protein accumulates at the plasma membrane. Furthermore, we showed that both myogenesis and cell-cell contact lead to a dramatic decrease of tyrosine phosphorylation level of PDGF receptor. In addition, we observed an increased association of the receptor with LMW-PTP during myogenesis. Herein, we demonstrate that myogenesis decreases the intracellular level of reactive oxygen species, as observed in dense cultures. As a consequence, LMW-PTP turns from oxidized to reduced form during muscle differentiation, increasing its activity in growth inhibition conditions such as differentiation. These data suggest that LMW-PTP plays a crucial role in physiological processes, which require cell growth arrest such as confluence and differentiation.

Impact of Cu(II) and Ni(II) on a structure of chiral peptide nucleic acids having four, six and eight thymines in a peptide side chain.

The studies on binding ability of longer chiral peptide nucleic acids (having four, six and eight thymines in a peptide side chain) have shown that the interactions between the nucleic base rings within a ligand molecule have a critical impact on the complex stability. Thymines inserted in the peptide side chain interact with each other as well as with peptide back-bone increasing the structural organization of the cPNA molecule. The metal ion coordination to cPNA, on the other hand, induces a very specific ligand structure, which may have a basic impact on the cPNA self-recognition processes.

Small ring constrained peptidomimetics. Synthesis of epoxy peptidomimetics, inhibitors of cysteine proteases.

Different dipeptide analogues containing an oxirane ring in the place of the peptidic bond were prepared starting from naturally occurring amino acids. N-Fmoc-amino aldehydes were transformed into the corresponding methoxyvinyl derivatives through a Wittig reaction, and the addition of PhSeCl gave a series of different alpha-phenylselenyl aldehydes. Mukajiama reaction with silylketene acetals gave an intermediate product that was finally transformed into the desired oxiranyl peptidomimetics. Following this strategy we were able to control three new contiguous stereocenters starting from the enantiomerically pure amino acid. The dipeptide analogues could be used in SPPS on a SASRIN resin as the final epoxides were relatively unstable under acidic conditions. Moreover the synthesis of the single dipeptide mimetics was carried out on solid phase to generate a small library of epoxy peptidomimetics. Some of the products prepared in this work resulted as time-dependent reversible inhibitors of cysteine protease.

Two vicinal cysteines confer a peculiar redox regulation to low molecular weight protein tyrosine phosphatase in response to platelet-derived growth factor receptor stimulation.

Low molecular weight protein tyrosine phosphatase (LMW-PTP) is an enzyme involved in platelet-derived growth factor (PDGF)-induced mitogenesis and cytoskeleton rearrangement because it is able to bind and dephosphorylate the activated receptor. LMW-PTP presents two cysteines in positions 12 and 17, both belonging to the catalytic pocket; this is a unique feature of LMW-PTP among all protein tyrosine phosphatases. Our previous results demonstrated that in vitro LMW-PTP is oxidized by either H(2)O(2) or nitric oxide with the formation of a disulfide bond between Cys-12 and Cys-17. This oxidation leads to reversible enzyme inactivation because treatment with reductants permits catalytic activity rescue. In the present study we investigated the in vivo inactivation of LMW-PTP by either extracellularly or intracellularly generated H(2)O(2), evaluating its action directly on its natural substrate, PDGF receptor. LMW-PTP is oxidized and inactivated by exogenous oxidative stress and recovers its activity after oxidant removal. LMW-PTP is oxidized also during PDGF signaling, very likely upon PDGF-induced H(2)O(2) production, and recovers its activity within 40 min. Our results strongly suggest that reversibility of in vivo LMW-PTP oxidation is glutathione-dependent. In addition, we propose an intriguing and peculiar role of Cys-17 in the formation of a S-S intramolecular bond, which protects the catalytic Cys-12 from further and irreversible oxidation. On the basis of our results we propose that the presence of an additional cysteine near the catalytic cysteine could confer to LMW-PTP the ability to rapidly recover its activity and finely regulate PDGF receptor activation during both extracellularly and intracellularly generated oxidative stress.

Solid-phase synthesis of beta-lactams via the Miller hydroxamate approach.

[figure: see text] beta-Lactams were prepared on solid phase starting from serine, threonine, or other beta-hydroxyacids derived from naturally occurring amino acids and a resin bound hydroxylamine. The ring closure was carried out under Mitsunobu conditions. The amino group present on the beta-lactam was used to assemble a short peptide. After a reductive cleavage with Sml2, beta-lactam-containing peptides were obtained.