Metamagnetic Anomalies near Dynamic Phase Transitions.

We report the existence of anomalous metamagnetic fluctuations in the vicinity of the dynamic phase transition (DPT) that do not occur for the corresponding thermodynamic behavior of simple ferromagnets. Our results demonstrate that key characteristics associated with the DPT are qualitatively different from conventional thermodynamic phase transitions. We also provide evidence that these differences are tunable by showing that the presence of metamagnetic fluctuations and the size of the critical scaling regime depend strongly on the amplitude of the oscillating field that is driving the DPT in the first place.

Polarization conversion-based molecular sensing using anisotropic plasmonic metasurfaces.

Anisotropic media induce changes in the polarization state of transmitted and reflected light. Here we combine this effect with the refractive index sensitivity typical of plasmonic nanoparticles to experimentally demonstrate self-referenced single wavelength refractometric sensing based on polarization conversion. We fabricated anisotropic plasmonic metasurfaces composed of gold dimers and, as a proof of principle, measured the changes in the rotation of light polarization induced by biomolecular adsorption with a surface sensitivity of 0.2 ng cm(-2). We demonstrate the possibility of miniaturized sensing and we show that experimental results can be reproduced by analytical theory. Various ways to increase the sensitivity and applicability of the sensing scheme are discussed.

Nanopatterning reconfigurable magnetic landscapes via thermally assisted scanning probe lithography.

The search for novel tools to control magnetism at the nanoscale is crucial for the development of new paradigms in optics, electronics and spintronics. So far, the fabrication of magnetic nanostructures has been achieved mainly through irreversible structural or chemical modifications. Here, we propose a new concept for creating reconfigurable magnetic nanopatterns by crafting, at the nanoscale, the magnetic anisotropy landscape of a ferromagnetic layer exchange-coupled to an antiferromagnetic layer. By performing localized field cooling with the hot tip of a scanning probe microscope, magnetic structures, with arbitrarily oriented magnetization and tunable unidirectional anisotropy, are reversibly patterned without modifying the film chemistry and topography. This opens unforeseen possibilities for the development of novel metamaterials with finely tuned magnetic properties, such as reconfigurable magneto-plasmonic and magnonic crystals. In this context, we experimentally demonstrate spatially controlled spin wave excitation and propagation in magnetic structures patterned with the proposed method.

Enhanced Magneto-Optical Edge Excitation in Nanoscale Magnetic Disks.

We report unexpected enhancements of the magneto-optical effect in ferromagnetic Permalloy disks of diameter D<400 nm. The effect becomes increasingly pronounced for smaller D, reaching more than a 100% enhancement for D=100 nm samples. By means of experiments and simulations, the origin of this effect is identified as a nanoscale ring-shaped region at the disk edges, in which the magneto-optically induced electric polarization is enhanced. This leads to a modification of the electromagnetic near fields and causes the enhanced magneto-optical excitation, independent from any optical resonance.

Segregation of materials in double precursor electron-beam-induced-deposition: a route to functional magnetic nanostructures.

Here we report an observation of the phenomenon of spatial segregation of two materials in double precursor electron beam induced deposition. Segregation occurs under proper deposition conditions in a single spot illumination due to generic variation of electron current density within an electron beam. Combining precursors for magnetic (dicobaltoctacarbonyl) and non-magnetic (tetraethyl orthosilicate) properties we demonstrate a one-step fabrication process for magnetic tubules at the scale of 100 nm. Electron holography applied on the cross-section of thus prepared tubules reveals the concentration of the magnetic field in the cobalt rich shell, corroborating spatially distributed functionality. We elaborate the numerical model describing the observed phenomenon and defining the conditions for its practical achievement.

Transient behavior of the dynamically ordered phase in uniaxial cobalt films.

We study the time dependent magnetic behavior of uniaxial cobalt films in the vicinity of the dynamic phase transition (DPT) as a function of the period P and bias H(b) of an oscillating magnetic field. In addition to the DPT at a critical period P(c), we observe the occurrence of transient behavior for P

Fabrication and magnetic characterization of cobalt antidot arrays: effect of the surrounding continuous film.

We have performed an experimental study on the influence of a ferromagnetic continuous film in the magnetization reversal processes in discrete submicrometric antidot arrays fabricated on it. In order to compare the magnetic properties, two sets of antidot arrays have been fabricated over a cobalt thin film: embedded in the continuous film, and isolated by a trench surrounding the array. X-ray photoemission electron microscopy images of the virgin state show the same magnetic domain distribution in both sets of samples, finding no evidence of any effect of the surrounding film. This result is supported by the hysteresis loops measured with magneto-optical Kerr effect, as isolated and non-isolated arrays present almost coincident loops. A huge increase of the coercivity of the film is achieved, and the expected dependence on the geometrical parameters of the array is found, connecting the previous studies on the micro- and nanometric scales.

Magnetic domain wall conduits for single cell applications.

The ability to trap, manipulate and release single cells on a surface is important both for fundamental studies of cellular processes and for the development of novel lab-on-chip miniaturized tools for biological and medical applications. In this paper we demonstrate how magnetic domain walls generated in micro- and nano-structures fabricated on a chip surface can be used to handle single yeast cells labeled with magnetic beads. In detail, first we show that the proposed approach maintains the microorganism viable, as proven by monitoring the division of labeled yeast cells trapped by domain walls over 16 hours. Moreover, we demonstrate the controlled transport and release of individual yeast cells via displacement and annihilation of individual domain walls in micro- and nano-sized magnetic structures. These results pave the way to the implementation of magnetic devices based on domain walls technology in lab-on-chip systems devoted to accurate individual cell trapping and manipulation.

Elastic and magnetic dynamics of nanomagnet-ordered arrays impulsively excited by subpicosecond laser pulses.

This Letter reports on the first observation of elastic and magnetic dynamics of ordered arrays of permalloy nanodots excited by low-intensity 120 fs light pulses. The first order of the diffraction pattern, generated by the probe beam in a pump-probe configuration, is used for time-resolved reflectivity and time-resolved magneto-optical Kerr effect measurements. The nonadiabatical absorption of the pump triggers an acoustic standing wave, detected by the reflected probe signal, with a frequency related to the array wave vector. Instead, the magneto-optical signal exhibits, on the nanosecond time scale, the signature of the heat-exchange diffusion processes. In addition, a clear oscillation of the magnetic signal, at a frequency close to the frequency of the acoustic wave, is unambiguously detected. Finally, the interplay between the elastic and magnetic dynamics is analyzed and interpreted.

Dynamic origin of stripe domains.

We investigate stripe domain formation in nanometer sized Co bars. The magnetic equilibrium states and the magnetic spin wave frequencies are obtained from micromagnetic-like simulations. We find that the lowest frequency standing-wave mode has the same spatial structure as the stripe domains at remanence and it goes soft at the field where the stripe domains emerge. We show, therefore, that the final domain structure at remanence, which is not the configuration with lowest energy, is predicted from a high-field analysis of the frequencies of the standing spin waves.

Silencing of SH-PTP2 defines a crucial role in the inactivation of epidermal growth factor receptor by 5-aminosalicylic acid in colon cancer cells.

Recent studies have suggested that 5-aminosalicylic acid (5-ASA) inhibits colorectal cancer (CRC) development. However, the mechanism underlying the antineoplastic effect of 5-ASA remains unknown. We here examined the effect of 5-ASA on epidermal growth factor receptor (EGFR) activation, a pathway that triggers mitogenic signals in CRC cells. We show that 5-ASA inhibits EGFR activation, through a mechanism that does not rely on CRC cell death induction. 5-ASA enhances the activity, but not expression, of phosphorylated (p)-EGFR-targeting phosphatases (PTPs), and treatment of cells with PTP inhibitors abrogates the 5-ASA-mediated EGFR dephosphorylation. Both SH-PTP1 and SH-PTP2 interact with EGFR upon 5-ASA treatment. However, knockdown of SH-PTP2 but not SH-PTP1 by small interference RNAs prevents the 5-ASA-induced EGFR dephosphorylation. Finally, we show that 5-ASA attenuates p-EGFR in ex vivo organ cultures of CRC explants. Data indicate that 5-ASA disrupts EGFR signalling by enhancing SH-PTP2 activity, and suggest a mechanism by which 5-ASA interferes with CRC growth.

Regulation of the T helper cell type 1 transcription factor T-bet in coeliac disease mucosa.

BACKGROUND: In coeliac disease (CD) mucosa, the histological lesion is associated with marked infiltration of T helper cell type 1 (Th1) cells. However, the molecular mechanisms which regulate Th1 cell differentiation in CD mucosa are unknown. AIMS: To analyse expression of transcription factors which control the Th1 cell commitment in CD. PATIENTS: Duodenal mucosal samples were taken from untreated CD patients and normal controls. METHODS: Interferon gamma (IFN-gamma) and interleukin (IL)-4 RNA expression was examined in T lamina propria lymphocytes by quantitative reverse transcription-polymerase chain reaction. T-bet and STAT-4, two Th1 promoting transcription factors, and STAT-6 and GATA-3, transcription factors which govern T helper cell type 2 (Th2) cell polarisation, were examined in duodenal biopsies by western blotting. The effect of gliadin and IFN-gamma on expression of T-bet was examined in an ex vivo culture of biopsies taken from normal and treated CD patients. RESULTS: As expected, IFN-gamma but not IL-4 RNA transcripts were increased in the mucosa of CD patients in comparison with controls. CD mucosal samples consistently exhibited higher levels of T-bet than controls. However, no difference in active STAT-4 expression was seen between CD patients and controls, suggesting that Th1 polarisation was not induced by local IL-12. GATA-3 and STAT-6 were also low in both CD and control mucosa. In normal duodenal biopsies, IFN-gamma stimulated T-bet through a STAT-1 dependent mechanism. Challenge of treated CD but not control biopsies with gliadin enhanced T-bet and this effect was also inhibited by STAT-1 inhibition. CONCLUSIONS: This study shows that activation of STAT-1 by IFN-gamma promotes T-bet in CD mucosa.

Intra-oesophageal distribution and perception of acid reflux in patients with non-erosive gastro-oesophageal reflux disease.

BACKGROUND: The majority of patients with gastro-oesophageal reflux disease do not present with erosive oesophagitis and make up a heterogeneous group. Patients with non-erosive gastro-oesophageal reflux disease are less responsive than patients with oesophagitis to acid-suppressive therapy. AIM: To assess the role of acid reflux in gastro-oesophageal reflux disease symptoms. METHODS: The spatio-temporal characteristics of reflux events were analysed and related to reflux perception in 45 patients with non-erosive gastro-oesophageal reflux disease and 20 patients with erosive oesophagitis. RESULTS: Compared with healthy controls, all patients showed a higher intra-oesophageal proximal spread of acid, which was prominent in patients with non-erosive gastro-oesophageal reflux disease (> 50% of events lasting for 1-2 min). Irrespective of mucosal injury, the risk of reflux perception was very high when acid reached proximal sensors (odds ratio, 7.6; 95% confidence interval, 4.6-12.5), being maximal in patients with non-erosive gastro-oesophageal reflux disease with normal acid exposure time (odds ratio, 11; 95% confidence interval, 5.2-22.3). CONCLUSIONS: Patients with non-erosive gastro-oesophageal reflux disease are characterized by a significantly higher proportion of proximal acid refluxes and a higher sensitivity to short-lasting refluxes when compared with patients with oesophagitis. The highest proximal acid exposure and highest perception occurred in patients with non-erosive gastro-oesophageal reflux disease presenting with a normal pH-metric profile. The assessment of acid distribution and its perception in the oesophageal body can better identify reflux patients who should benefit from acid-suppressive treatment.

Exchange-induced anisotropies at ferromagnetic-antiferromagnetic interfaces above and below the Néel temperature.

The exchange bias and magnetic anisotropies in a Co layer on a single-crystalline FeF2 film have been determined between 30 and 300 K. By postulating that the coupling between the ferromagnet and the antiferromagnet persists above the Néel temperature (T(N)) we develop a model that quantitatively describes the exchange bias and the anisotropies over the whole temperature range, both above and below T(N). Using only the measured low temperature exchange bias and a distribution of blocking temperatures we explain (i) the temperature dependence of the bias, (ii) the magnitude of the anisotropies, (iii) the opposite sign of the first and second order anisotropies, (iv) the observed 1/T and 1/T(3) temperature dependencies of the first and second order uniaxial anisotropies above T(N), and (v) the decrease of the anisotropies below T(N).

Cytoskeletal proteins and resident flora.

Recent observations demonstrate that enteropathogenetic and enterohaemorrhagic bacteria, as well as other non enteropathogenetic bacteria (Listeria, Coxiella Burnetii), may subvert the host cell cytoskeleton. Models from enteropathogenic bacteria demonstrate that cytoskeletal proteins are required for bacteria binding to the enterocytes and that they play a role in the immune response of the host to intestinal bacteria. The cytoskeletal protein family Tropomyosins is present in all eukaryotic cells, with multiple isoforms regulated by multiple genes. Of the different Tropomyosin isoforms, TM5 has been shown to be expressed in colonic and jejunal epithelial cells, while TM1 in colonic and jejunal smooth muscle. In vitro studies have shown the presence of serum and mucosal IgG against TM5 in almost two thirds of patients with ulcerative colitis, suggesting: a. a possible autoimmune response to Tropomyosin in these patients; b. the hypothesis that the development of pouchitis may be related to the expression of TM5 in the ileal pouch; c. the use of probiotics in the treatment of pouchitis. Overall, the new expression of cytoskeletal proteins on the cell surface appears to be possibly induced by several mechanisms, including intestinal bacteria and apoptosis. The expression of cytoskeletal proteins on the cell surface may induce tolerance or autoimmune response on target cells. Further investigations are, however needed on the possible role of cytoskeletal proteins in human diseases.

Resident bacterial flora and immune system.

The "controlled inflammation" of the normal human gut is a closely controlled phenomenon and any change in the cell type number and/or functions, including the release of soluble mediators can lead to an "uncontrolled" inflammation. The physiological inflammation in the human gut plays a crucial role in maintaining a local immune response that is appropriate, efficiently protective and which respects the gut structure and function. The intestinal mucosa represents a considerable proportion of the human immune system. Disregulation of the mucosal immune response can switch a "controlled" toward an "uncontrolled" intestinal inflammation. A key role in the maintenance of an adequate balance between antigenic stimulation and host immune response is played by the immunoregulatory molecules released by activated immunocytes in the human gut. The role of the host immune system in the maintenance of an adequate balance between luminal antigens, including the resident bacterial flora and host immune response, is strongly supported by animal models of uncontrolled intestinal inflammation. Besides the aetiology of inflammatory bowel disease, luminal antigens (including food, viral and bacterial antigens) contribute to the maintenance of the inflammatory process in inflammatory bowel disease, by stimulating the immunocompetent cells in the intestinal mucosa. Of the luminal antigens, the resident bacterial flora seems to play a major role in the development of animal models of "uncontrolled" intestinal inflammation. Recent evidence also suggest that bacterial flora can modulate the function of the intestinal mucosal cells. These observations support the role of the intestinal bacterial flora in the induction of an uncontrolled inflammation in the human gut, leading to tissue damage. Probiotics, defined as living micro-organisms which, when taken in appropriate amounts, improve the health status, have been proposed in the treatment of inflammatory bowel disease, but their mechanisms of action still remain to be fully elucidated.

Review article: monitoring the activity of Crohn's disease.

Crohn's disease is characterized by a chronic inflammation of the intestine of unknown aetiology. One of the main problems when treating patients with Crohn's disease, is the identification of patients undergoing early clinical relapse, for timely treatment and the possible prevention of complications. No sub-clinical markers are currently available that predict relapse during remission. Several parameters have been proposed for this purpose. Although none have proven useful, growing evidence suggests a possible benefit in the clinical management of Crohn's disease. Among these, we may identify: clinical behaviour, the characteristics of the host, clinical activity, markers of intestinal inflammation and markers of immune activation. In particular, the possible relationship between cytokine pattern and the clinical behaviour of Crohn's disease has been addressed. Overall, these observations suggest that mucosal immune activation is a feature of Crohn's disease, and may persist in the form of activated immunocompetent cells during remission. On the basis of this evidence, studies are currently investigating whether the down-regulation of immune activation markers is associated with clinical remission in Crohn's disease. It has been shown that higher mucosal levels of TNF-alpha and an increased state of activation of lamina propria mononuclear cells in patients with inactive Crohn's disease, are significantly associated with an earlier clinical relapse of the disease. These observations suggest that a persistent local immune activation during remission may represent a marker of early clinical relapse of Crohn's disease.

Outcome of endoscopic sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction as predicted by manometry and quantitative choledochoscintigraphy.

BACKGROUND: Sphincter of Oddi dysfunction is diagnosed at manometry and, after cholecystectomy, non-invasively at quantitative choledochoscintigraphy. Patients may benefit from endoscopic sphincterotomy. AIMS: The aim of this study was to assess the usefulness of choledochoscintigraphy compared with manometry in predicting outcome of sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction. PATIENTS AND METHODS: Thirty patients with biliary-type pain complying with the Rome diagnostic criteria of sphincter of Oddi dysfunction and belonging to biliary group I and II were subjected to clinical evaluation, choledochoscintigraphic assessment of the hepatic hilum-duodenum transit time, endoscopic retrograde cholangiopancreatography, and perendoscopic manometry. Twenty two biliary group I and II patients with prolonged hepatic hilum-duodenum transit times were invited to undergo sphincterotomy. Fourteen patients underwent sphincterotomy; eight refused. Clinical and scintigraphic assessments were performed at follow up. RESULTS: Hepatic hilum-duodenum transit time was delayed in all patients with manometric evidence of sphincter of Oddi dysfunction, in all biliary group I patients and in 64% of biliary group II patients. At follow up, all patients who underwent sphincterotomy were symptom free and hepatic hilum-duodenum transit time had either normalised or significantly improved. A favourable post sphincterotomy outcome was predicted in 93% of cases at choledochoscintigraphy and in 57% at manometry. CONCLUSIONS: Quantitative choledochoscintigraphy is a useful and non-invasive test to diagnose sphincter of Oddi dysfunction as well as a reliable predictor of sphincterotomy outcome in post cholecystectomy biliary group I and II patients, irrespective of clinical classification and manometric findings.

Immunoregulation in the gut: success and failures in human disease.

In normal conditions, human gut mucosa is infiltrated with a large number of mononuclear cells. This is a reflection of the fact that human intestine is continuously subjected to a massive stimulation by luminal antigens. This state of "physiological" inflammation is a tightly controlled phenomenon, as several mucosal cells interact to generate and maintain an appropriate local immune response. Changes in cell type number and/or function, including the release of soluble mediators, have been associated with the development of chronic inflammatory diseases, such as Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease. Evidence also indicates that the type of inflammatory response occurring in the intestine of patients with CD differs from that in UC, and this probably reflects distinct pathways of immune activation. In CD mucosa, a Th1 response with high IL-12 and IFNgamma production prevails, while in UC a humoral immunity appears to be predominant. Despite this, CD and UC share downstream inflammatory events, characterised by high levels of inflammatory cytokines, free radicals, matrix-degrading enzymes and growth factors.