Characterization of Er in porous Si

The fabrication of porous Si-based Er-doped light emitting devices is a very promising developing field for all-silicon light emitters. However, while luminescence of Er-doped porous silicon devices has been demonstrated, very little attention has been devoted to the doping process itself. We have undertaken a detailed study of this process examining the porous silicon matrix from several points of view, during and after the doping. In particular, we have found that the Er doping process shows a threshold level which, as evidenced by the cross correlation of the various techniques used, does depend on the sample thickness and on the doping parameters

Ankle Bipolar Fresh Osteochondral Allograft Survivorship and Integration: Transplanted Tissue Genetic Typing and Phenotypic Characteristics

Il trapianto fresco bipolare o allograft di caviglia puo rappresentare una valida alternative nel trattamento dell’artrosi post-traumatica nel paziente giovane ed attivo. Nonostante l’utilizzo di tale procedura, poco si conosce sulla ricolonizzazione del trapianto osteocondrale da parte delle cellule del ricevente. Scopo di questo studio era definire il profilo genotipico di prelievi bioptici eseguiti da allograft di caviglia a 21 mesi di follow-up. 22 allograft sono stati inclusi nello studio. Lo score clinico AOFAS e la valutazione radiologica è stata eseguita al follow-up finale di 61±13.6 mesi. 22 prelievi bioptici sono stati prelevati ad una media di 21 mesi di FU. Sono stati analizzati con valutazione istologica ed immunoistochimica. 20 prelievi sono stati confrontati mediante typing genetico con il DNA del donatore e del ricevente. In 6 casi è stata associata una valutazione fenotipica della popolazione cellulare rinvenuta nel prelievo bioptico con valutazione dell’espressione genica. Abbiamo osservato 2 fallimenti. Lo score AOFAS è passato da un valore pre-operatorio di 25,7 ± 8.0 punti a 76.2±14.1 (p<0.05) al follow up finale. L’analisi genotipica ha mostrato una popolazione compatibile con il ricevente in 12 casi, una popolazione mista ricevente donatore in 5 e la presenza esclusiva di cellule del donatore in 3. L’analisi dell’espressione genica ha evidenziato markers specifici della linea cartilaginea. L’analisi genotipica e le valutazioni istologiche ed immunoistochimiche suggeriscono una migrazione di cellule del ricevente nella porzione cartilaginea dell’allograft a partenza dall’osso subcondrale. L’analisi dell’espressione genica sembra suggerire che queste cellule, una volta migrate, possano differenziarsi nella linea cartilaginea.Ankle bipolar fresh osteochondral allograft may represent a valid alternative in the treatment of sever post-traumatic ankle arthritis in young and active patients. Despite the widespread use of this procedure little is known about allograft recolonization by host cells. Aim of this study was to assess the genotypic profile and the phenotypic pattern of retrieved specimens from ankle allografts at 21 months follow-up. 22 ankle allografts were included in the study. AOFAS clinical score and radiographic evaluation was performed up to the final follow-up of 61±13.6 months. 22 bioptic specimens harvested at 21 months follow-up were analyzed by histological and immunohistochemical analysis. 20 specimens were compared with recipient and donor constitutional DNA by genotyping. In 6 cases gene expression was evaluated by means of real-time reverse transcription-polymerase chain reaction. We observed 2 failures. AOFAS score improved from 25,7 ± 8.0 points pre-operatively to 77,5 ±11,2 at 12 months follow-up and 76.2±14.1 (p<0.05) at final follow-up. Genotyping on allograft retrieved specimens showed an exclusive recipient cellular population in 12 cases, a mixed profile in 5 cases and exclusive presence of donor cells in 3 cases. Gene expression analysis showed that grafted cartilage expressed cartilage-specific markers. The genotyping analysis along with histological and immunohistochemical evaluations suggest the ingrowth of host cells into the transplanted cartilage migrating from the subchondral bone and crossing the tidemark. Gene expression analysis seems to suggest that these cells, once migrated, may differentiate toward cartilaginous lineage

Reversible normalisation of serum TSH levels in patients with autoimmune atrophic gastritis who received L-T4 in tablet form after switching to an oral liquid formulation: A case series

Background: L-thyroxine (L-T4) malabsorption is a potential concern in patients with autoimmune atrophic gastritis. Methods: We evaluated five patients with autoimmune gastritis, who showed high serum thyrotropin (TSH) levels (in the hypothyroid range) while in therapy with L-T4 in tablet. All patients were switched to receive an oral L-T4 liquid formulation maintaining the same dosage. Results: In all patients who received L-T4 in tablet form after switching to an oral liquid formulation with the same L-T4 dosage, TSH circulating levels were normalized. In four patients who were switched back again to receive L-T4 in tablets, maintaining the dosage, TSH levels worsened again reaching levels in the hypothyroid range. Conclusions: The fact that the change from tablets to liquid oral formulation normalised serum TSH levels, and that switching back to tablets caused thyrotropin levels to worsen, leads us to believe that absorption of L-T4 is greater with oral liquid formulations in these patients. These results suggest that the L-T4 oral liquid formulation could circumvent the pH alteration resulting from atrophic gastritis

Controlling the Er content of porous silicon using the doping current intensity

The results of an investigation on the Er doping of porous silicon are presented. Electrochemical impedance spectroscopy, optical reflectivity, and spatially resolved energy dispersive spectroscopy (EDS) coupled to scanning electron microscopy measurements were used to investigate on the transient during the first stages of constant current Er doping. Depending on the applied current intensity, the voltage transient displays two very different behaviors, signature of two different chemical processes. The measurements show that, for equal transferred charge and identical porous silicon (PSi) layers, the applied current intensity also influences the final Er content. An interpretative model is proposed in order to describe the two distinct chemical processes. The results can be useful for a better control over the doping process

Impaired sense of smell in a Drosophila Parkinson's model.

Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by the clinical triad: tremor, akinesia and rigidity. Several studies have suggested that PD patients show disturbances in olfaction at the earliest onset of the disease. The fruit fly Drosophila melanogaster 32 is becoming a powerful model organism to study neurodegenerative diseases. We sought to use this system to explore olfactory dysfunction, if any, in PINK1 mutants, which is a model for PD. PINK1 mutants display many important diagnostic symptoms of the disease such as akinetic motor behavior. In the present study, we describe for the first time, to the best of our knowledge, neurophysiological and neuroanatomical results concerning the olfactory function in PINK1 mutant flies. Electroantennograms were recorded in response to synthetic and natural volatiles (essential oils) from groups of PINK1 mutant adults at three different time points in their life cycle: one from 3-5 day-old flies, from 15-20 and from 27-30 days. The results obtained were compared with the same age-groups of wild type flies. We found that mutant adults showed a decrease in the olfactory response to 1-hexanol, α-pinene and essential oil volatiles. This olfactory response in mutant adults decreased even more as the flies aged. Immunohistological analysis of the antennal lobes in these mutants revealed structural abnormalities, especially in the expression of Bruchpilot protein, a marker for synaptic active zones. The combination of electrophysiological and morphological results suggests that the altered synaptic organization may be due to a neurodegenerative process. Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology. These results help to explore the potential of using olfaction as a means of monitoring PD progression and developing new treatments

Lenvatinib exhibits antineoplastic activity in anaplastic thyroid cancer in vitro and in vivo

Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages. The effect of lenvatinib (1 and 100 nM; and 1, 10, 25 and 50 μM) was investigated in primary ATC, 8305C and AF cells as well as in AF cells in CD nu/nu mice. Lenvatinib significantly reduced ATC cell proliferation (P<0.01, ANOVA) and increased the percentage of apoptotic ATC cells (P<0.001, ANOVA). Furthermore, lenvatinib inhibited migration (P<0.01) and invasion (P<0.001) in ATC. In addition, lenvatinib inhibited EGFR, AKT and ERK1/2 phosphorylation and downregulated cyclin D1 in the ATC cells. Lenvatinib also significantly inhibited 8305C and AF cell proliferation, increasing apoptosis. AF cells were subcutaneously injected into CD nu/nu mice and tumor masses were observed 20 days later. Tumor growth was significantly inhibited by lenvatinib (25 mg/kg/day), as well as the expression of VEGF-A and microvessel density in the AF tumor tissues. In conclusion, the antitumor and antiangiogenic activities of lenvatinib may be promising for the treatment of anaplastic thyroid cancer, and may consist a basis for future clinical therapeutic applications

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus

Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients

Vandetanib has antineoplastic activity in anaplastic thyroid cancer, in vitro and in vivo

The antitumor activity of vandetanib [a multiple signal transduction inhibitor including the RET tyrosine kinase, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor (VEGFR), ERK and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C [undifferentiated thyroid cancer (TC)] and in an ATC-cell line (AF), was investigated in the present study. Vandetanib (1 and 100 nM; 1, 10, 25 and 50 μM) was tested by WST-1, apoptosis, migration and invasion assays: in primary ATC cells, in the 8305C continuous cell line, and in AF cells; and in 8305C cells in CD nu/nu mice. Vandetanib significantly reduced ATC cell proliferation (P<0.01, ANOVA), induced apoptosis dose-dependently (P<0.001, ANOVA), and inhibited migration (P<0.01) and invasion (P<0.001). Furthermore, vandetanib inhibited EGFR, AKT and ERK1/2 phosphorylation and downregulated cyclin D1 in ATC cells. In 8305C and AF cells, vandetanib significantly inhibited the proliferation, inducing also apoptosis. 8305C cells were injected subcutaneously in CD nu/nu mice and tumor masses became detectable after 30 days. Vandetanib (25 mg/kg/day) significantly inhibited tumor growth and VEGF-A expression and microvessel density in 8305C tumor tissues. In conclusion, the antitumor and antiangiogenic activity of vandetanib is very auspicious in ATC, opening the way to a future clinical evaluation

Operational research and the Royal Canadian Air Force Eastern Air Command\u27s search for efficiency in airborne anti-submarine warfare, 1942-1945

This thesis analyses the contributions of operational research to the work of the Royal Canadian Air Force Eastern Air Command during the Second World War. The efforts of the handful of Canadian operational researchers in the Allied campaign against the German U-boat force, although having produced only modest results, did make a small but important contribution to the war which have been neglected by historians. The use of aircraft against submarines began during the First World War when both technologies were still in their infancy. Although initial results were poor, the handful of sinkings by aircraft demonstrated its potential as a counter to the seemingly invulnerable submarine. Great Britain, with its vulnerable seaward lines of communication, emerged by 1918 as the leader in the development of anti-submarine aircraft, largely through the co-operative efforts of scientists and airmen to refine and advance the concept of airborne anti-submarine warfare. Although much of this knowledge was squandered through the neglect of the Royal Air Force’s land-based anti-submarine aircraft force during the inter-war period, the early introduction of scientists to the field of airborne anti-submarine warfare provided a precedent for a future revival of this relationship. The techniques of operational research, first promulgated during the British experiments with radar during the 1930s, were, by 1941, applied to assist Royal Air Force Coastal Command in its campaign against the German U-boats which were taking an ever-increasing toll of Allied shipping. The work of P.M.S. Blackett and his staff at Coastal Command Operational Research Section would serve as the foundation upon which Eastern Air Command’s Operational Research Section (ORS) would be constructed when it was created in November 1942. Under the leadership of Professor Colin Barnes and later Dr. J.W.T. Spinks, Eastern Air Command ORS produced a series of studies which explored issues of concern to the Command’s anti-submarine (bomber-reconnaissance) squadrons. They used methodologies adapted for Canadian purposes from the original British and American models. These studies of diverse topics such as bombing accuracy and search techniques for missing aircraft, along with the squadron and Command efficiency data collected in operational planning role assumed by Eastern Air Command ORS (one which had earlier been rejected as unproductive clerical work by Coastal Command ORS), characterized the growth of Canadian-oriented operational research during the final three years of the Second World War. The work of the handful of civilian and military operational researchers at Eastern Air Command ORS, although threatened with elimination during the deep cuts to the military in the immediate post-war years, survived to form part of the body of Canadian military operational research techniques which has assisted the Canadian Forces in their duties throughout the last half-century