ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Adenocarcinoma/physiopathology , Colorectal Neoplasms/physiopathology , ErbB Receptors/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Mesalamine/pharmacology , Protein Tyrosine Phosphatases/metabolism , Adenocarcinoma/enzymology , Adenocarcinoma/genetics , Apoptosis/drug effects , Apoptosis/physiology , Blotting, Western , Cell Line, Tumor , Cell Proliferation/drug effects , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/genetics , Enzyme Activation , ErbB Receptors/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Immunoprecipitation , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/physiology , Male , Phosphorylation , Protein Tyrosine Phosphatase, Non-Receptor Type 11 , Protein Tyrosine Phosphatase, Non-Receptor Type 6 , Protein Tyrosine Phosphatases/genetics , Protein Tyrosine Phosphatases/physiology , RNA Interference , RNA, Small Interfering/pharmacologyABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Patients with Crohn's disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-alpha (IFN-alpha) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00-2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04-11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61-3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37-3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37-3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06-1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-alpha for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.
Subject(s)
Crohn Disease/epidemiology , Crohn Disease/virology , Hepacivirus/immunology , Hepatitis B virus/immunology , Hepatitis B/epidemiology , Hepatitis C/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Colitis, Ulcerative/virology , Crohn Disease/complications , Crohn Disease/drug therapy , Female , Hepatitis Antigens/blood , Hepatitis B/complications , Hepatitis C/complications , Humans , Immunosuppressive Agents/therapeutic use , Interferon-alpha/therapeutic use , Italy/epidemiology , Male , Middle Aged , Multivariate Analysis , Prevalence , RNA, Viral/blood , Risk FactorsABSTRACT
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.
Subject(s)
Crohn Disease/diagnosis , Health Status Indicators , Biomarkers/analysis , Crohn Disease/immunology , Cytokines/metabolism , Humans , Prognosis , Recurrence , Severity of Illness IndexABSTRACT
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.
Subject(s)
Gastroesophageal Reflux/physiopathology , Adolescent , Adult , Aged , Esophagitis, Peptic/physiopathology , Esophagitis, Peptic/psychology , Female , Gastric Acid/chemistry , Gastroesophageal Reflux/psychology , Heartburn/etiology , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Perception , Recurrence , Risk FactorsABSTRACT
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.
Subject(s)
Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Anti-Bacterial Agents/therapeutic use , Crohn Disease/drug therapy , Crohn Disease/immunology , Humans , Inflammatory Bowel Diseases/immunology , Intestines/microbiology , Probiotics/therapeutic useABSTRACT
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.
Subject(s)
Cytoskeletal Proteins/metabolism , Intestines/microbiology , Humans , Pouchitis/etiology , Pouchitis/therapy , Probiotics/therapeutic use , Tropomyosin/metabolismABSTRACT
Impaired gallbladder motility may contribute to gallstone pathogenesis by providing time for nucleation and aggregation of cholesterol crystals. Simultaneous scintigraphic-ultrasonographic techniques have been proposed to assess alternating phases of gallbladder emptying and filling. To evaluate patterns of gallbladder motility and of postprandial bile flow by means of a single ultrasonographic technique, 12 healthy volunteers and 20 gallstone patients underwent minute-by-minute gallbladder ultrasonography for 3 h postprandially. Mathematical analysis of volume measurements was used to estimate hepatic and cholecystic bile flux through the gallbladder. Compared to controls, gallstone patients showed greater amounts of unexchanged cholecystic-to-hepatic bile (11% vs. 1%, p <.001) and most of them showed impaired gallbladder washout efficacy. Utrasonographic values of bile exchanges were similar to those derived from scintigraphic-sonographic studies in comparable groups of subjects. This study provides new ultrasonographic variables, which better express gallbladder bile retention in gallstone patients and strongly discriminate gallstone patients from controls.
Subject(s)
Cholelithiasis/diagnostic imaging , Cholestasis/diagnostic imaging , Gallbladder/diagnostic imaging , Liver/metabolism , Postprandial Period/physiology , Adult , Aged , Bile/metabolism , Cholelithiasis/physiopathology , Cholestasis/physiopathology , Female , Gallbladder/physiology , Gallbladder/physiopathology , Humans , Male , Middle Aged , Reference Values , Time Factors , UltrasonographyABSTRACT
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.