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The DebateQuestion 1: Various commentators have frequently invoked the importance of moderate Muslims and the role that they can play in fighting extremism in the Muslim world. But it is not clear who is a moderate Muslim. The recent cancellation of Tariq Ramadan’s visa to the United States, the raids on several American Muslim organizations, and the near marginalization of mainstream American Muslims in North America pose the following question: If moderate Muslims are critical to an American victory in the war on terror, then why does the American government frequently take steps that undermine moderate Muslims? Perhaps there is a lack of clarity about who the moderate Muslims are. In your view, who are these moderate Muslims and what are their beliefs and politics? JLE: Our human tendency is to define what is normal or moderate in terms of someone just like “us.” The American government, as well as many western and Muslim governments and experts, define moderate by searching for reflections of themselves. Thus, Irshad Manji or “secular” Muslims are singled out as self-critical moderate Muslims by such diverse commentators as Thomas Friedman or Daniel Pipes. In an America that is politicized by the “right,” the Republican and religious right, and post-9/11 by the threat of global terrorism and the association of Islam with global terrorism, defining a moderate Muslim becomes even more problematic. Look at the situations not only in this country but also in Europe, especially France. Is a moderate Muslim one who accepts integration, or must it be assimilation? Is a moderate Muslim secular, as in laic (which is really anti-religious)? Is a moderate Muslim one who accepts secularism, as in the separation of church and state, so that no religion is privileged and the rights of all (believer and nonbeliever) are protected? Is a moderate Muslim one who accepts a particular notion of gender relations, not simply the equality of women and men but a position against wearing hijab? (Of course let’s not forget that we have an analogous problem with many Muslims whose definition of being a Muslim, or of being a “good” Muslim woman, is as narrowly defined.) In today’s climate, defining who is a moderate Muslim depends on the politics or religious positions of the individuals making the judgment: Bernard Lewis, Daniel Pipes, Gilles Kepel, Stephen Schwartz, Pat Robertson, and Tom DeLay. The extent to which things have gotten out of hand is seen in attempts to define moderate Islam or what it means to be a good European or American Muslim. France has defined the relationship of Islam to being French, sought to influence mosques, and legislated against wearing hijab in schools. In the United States, non-Muslim individuals and organizations, as well as the government, establish or fund organizations that define or promote “moderate Islam,” Islamic pluralism, and so on, as well as monitor mainstream mosques and organizations. The influence of foreign policy plays a critical role. For some, if not many, the litmus test for a moderate Muslim is tied to foreign policy issues, for example, how critical one is of American or French policy or one’s position in regard to Palestine/Israel, Algeria, Kashmir, and Iraq. Like many Muslim regimes, many experts and ideologues, as well as publications like The Weekly Standard, National Review, The Atlantic, The New York Sun and media like Fox Television, portray all Islamists as being the same. Mainstream and extremist (they deny any distinction between the two) and indeed all Muslims who do not completely accept their notion of secularism, the absolute separation of religion and the state, are regarded as a threat. Mainstream Islamists or other Islamically oriented voices are dismissed as “wolves in sheep’s clothing.” What is important here is to emphasize that it is not simply that these individuals, as individual personalities, have influence and an impact, but that their ideas have taken on a life of their own and become part of popular culture. In a post-9/11 climate, they reinforce the worst fears of the uninformed in our populace. The term moderate is in many ways deceptive. It can be used in juxtaposition to extremist and can imply that you have to be a liberal reformer or a progressive in order to pass the moderate test, thus excluding more conservative or traditionalist positions. Moderates in Islam, as in all faiths, are the majority or mainstream in Islam. We assume this in regard to such other faiths as Judaism and Christianity. The Muslim mainstream itself represents a multitude of religious and socioeconomic positions. Minimally, moderate Muslims are those who live and work “within” societies, seek change from below, reject religious extremism, and consider violence and terrorism to be illegitimate. Often, in differing ways, they interpret and reinterpret Islam to respond more effectively to the religious, social, and political realities of their societies and to international affairs. Some seek to Islamize their societies but eschew political Islam; others do not. Politically, moderate Muslims constitute a broad spectrum that includes individuals ranging from those who wish to see more Islamically oriented states to “Muslim Democrats,” comparable to Europe’s Christian Democrats. The point here is, as in other faiths, the moderate mainstream is a very diverse and disparate group of people who can, in religious and political terms, span the spectrum from conservatives to liberal reformers. They may disagree or agree on many matters. Moderate Jews and Christians can hold positions ranging from reform to ultraorthodox and fundamentalist and, at times, can bitterly disagree on theological and social policies (e.g., gay rights, abortion, the ordination of women, American foreign and domestic policies). So can moderate Muslims.

Glasses with compositions falling in the Ca-Al-Si-O system are used to bond oxide ceramics. Alumina, zirconia and an alumina-zirconia composite are used as ceramic components. Joints are obtained at temperatures slightly higher than the melting temperature of glass which, for the selected compositions, change from 1210 to 1410oC. The degree of interaction between the ceramic components and the glass interlayer is mainly influenced by the bonding temperature and by the cooling rate. Conversely, the presence of defects like pores at the ceramic-glass interfaces depends on the experimental technique adopted to deposit the glass onto the ceramic surface. The 3-point flexural strength of the joint is measured at room temperature and for selected samples at 500oC. The mechanical properties of the joints are related to the microstructure at the interface.

Fired microstructures of standard porcelain stoneware tile and tile made from mixes containing waste glass as part of the flux system were studied by XRD, SEM, and TEM. The standard porcelain stoneware microstructure consists of 100-1000 μm long mullite needles, feldspar relics, and partially dissolved α-quartz embedded in a glassy matrix. The use of soda-lime-silica (SLS) glass in the flux system led to crystallization of plagioclase, wollastonite, and sodium silicates. CaO-rich areas adjacent to quartz particles, as a result of interactions between SLS glass and silica from the quartz, and eutectic morphologies, revealed that SLS glass accelerated liquid formation and thus sintering and densification. Formation of these additional phases led to lower levels of quartz, mullite, and Na-feldspar in the microstructure although lower firing temperatures could be used to achieve full density due to generation of more fluid liquid. Use of PbO-containing waste glasses had little effect on the microstructure compared with standard composition while use of mixed PbO-containing and SLS glasses led to microstructures containing plagioclase but to lower extent than in tile with higher levels of SLS.

In this paper, we show the regularity in Morrey spaces L2,λ for the gradient of minimizers of quasilinear functionals of the type We allow VMO dependence on the variable x and continuous dependence on the variable u.

The purpose of this study was to examine affective, behavioral, and cognitive functioning in adolescents with multiple suicide attempts. Forty-seven adolescents with a history of multiple suicide attempts (MA) were compared to 74 single suicide attempters (SA) on psychiatric diagnosis, depressive symptoms, affect regulation, self-mutilation, alcohol use, and hopelessness. Results revealed that the MA group was more likely to be diagnosed with a mood disorder, and reported more severe depressive symptoms and anger, in comparison to the SA group. Behaviorally, the MA group had higher rates of disruptive behavior disorders and higher levels of affect dysregulation and serious self-mutilation than the SA group. Further, greater levels of hopelessness were reported by the MA than the SA group. After controlling for a mood disorder diagnosis, only differences in anger, affect dysregulation, and serious self-mutilation remained significant. Overall, results suggest that treatment with adolescent suicide attempters might specifically target anger and affect dysregulation to reduce risk for future suicidal behavior.

Examined the relative importance of diagnostic and psychosocial factors in the prediction of adolescent suicidal ideation. Seventy-three high school students exhibiting emotional disturbance in the school setting completed a diagnostic interview and self-report measures assessing social support, family environment, negative life events, and problem solving. Using hierarchical regression analyses, only the presence of a pure internalizing disorder predicted suicidal ideation in addition to psychosocial variables. Interactions were found between psychiatric disorders and psychosocial variables. These results underscore the importance of including both diagnostic and psychosocial variables in research examining risk factors for adolescent suicidal behavior. Further, they suggest that adolescents presenting with psychiatric disorders, high levels of stress, and poor social support networks should be monitored for suicidality.

The aim of the present work is to obtain ceramic tiles with superior surface mechanical characteristics and chemical resistance, by the addition of nano-oxides, such as zirconia and alumina, since such advanced ceramics oxides are well known for their excellent mechanical properties and good resistance to chemical attack. In order to avoid any dangerousness, the nanoparticles were used in form of aqueous suspension and they were sprayed, by airbrush, directly onto the dried ceramic support, before firing. To observe the distribution of the nanoparticles and to optimise the surface treatment, SEM-EDS analyses were carried out on the fired samples. XRD analysis was conducted to assess the phase evolution of the different materials during the firing step. The surface mechanical characteristics of the samples have been evaluated by Vickers’ hardness and scratch test. In addition, chemical resistance tests were also performed. Microstructural observations allowed how alumina and zirconia nanoparticles acted to improve the surface performances of the modified ceramic tiles to be understood.

The possibility of recycling the Municipal Solid Wastes Incinerated (MSWI) bottom ash by its incorporation in ceramic tiles was investigated. The MSWI bottom ash was introduced both in untreated (previous deironization) and vitrified condition. The sintering of the different products was investigated by determining water absorption and linear shrinkage. To evaluate possible variations due to the presence of different amount of bottom ash, mineralogical and microstructural examinations by quantitative X-ray diffraction and scanning electron microscopy, were performed. While the untreated bottom ash, till an amount of 5 wt%, did not seem to affect the above characteristics of selected materials, the vitrified bottom ash, 5–10 wt%, as strong fluxing agent, promoted the sintering of porcelain stoneware. Leaching results allow to assert that the fired samples are not dangerous.

We report a case of temporomandibular disorder patient with disc displacement without reduction, myofascial pain, limited opening and a novel, never described, nonsynonimous mutation of catechol-O-methyl-transferase (COMT) gene. COMT is one of the enzymes that metabolizes catecholamines, thereby acting as a key modulator of dopaminergic and adrenergic/noradrenergic neurotransmissions, which play a key role in pain modulation. This novel mutation, p.R58S, changed a codon (58 from arginine to serine) in the COMT protein. The introduction of a serine residue in a highly organised secondary structure, in critical regions of the protein, results in a structural alteration. Therefore, we speculate an influence of the mutation on the high pain sensitivity of the patient.

At present the most interesting technology for the preparation of advanced opto-electronic devices seems to be the one based on semiconductor nanowires (NWs). Because of their high aspect ratio the NWs are the best candidates for the combination of highly mismatched semiconductors while maintaining good crystal quality. In particular, thanks to strain relaxation at the NW sidewalls, a reduction of the misfit dislocation density is possible, which is highly beneficial for device applications. In this regard interface sharpness is also a critical issue, especially for InAs/GaAs. In this work we present a study of the structure and strain relaxation in InAs/GaAs axial nanostructures in self-assisted NWs grown by MBE on (111) Si substrates. The growth was performed without the use of any catalyst. The top InAs segment is grown on the bottom self-assisted GaAs part of the NW via a two-step process by supplying In and As separately. The samples have been studied by High Resolution TEM (HR-TEM) as well as Scanning TEM (STEM) with a HAADF (High Angle Annular Dark Field) detector. HR-TEM showed that the InAs/GaAs is sharp at the atomic level, a result that has never been reported in the literature for MBE grown InAs/GaAs NWs. By STEM-HAADF the chemical transition between GaAs and InAs was seen to occur abruptly over a distance of 1.5 nm across the interface. The strain relaxation and related misfit dislocation (MD) generation were investigated by mapping the strain distribution obtained by processing HR-TEM images of the interface by the Geometrical Phase Analysis (GPA) method. MDs were detected as expected due to the size of about 70 nm of the NWs. However, their mutual distance increases radially on going from the NW center towards the sidewalls confirming that the strain was partially relaxed elastically at the sidewalls thus decreasing the formation probability of the MDs, i.e. their density. The latter experimental results have been compared with FEM (Finite Element Method) calculations with excellent agreement.

As the only fuel that is not chemically bound to carbon, hydrogen has gained interest as an energy carrier to face the current environmental issues of greenhouse gas emissions and to substitute the depleting non-renewable reserves. In the last years, there has been a significant increase in the number of publications about the bacterium Thermotoga neapolitana that is responsible for production yields of H2 that are among the highest achievements reported in the literature. Here we present an extensive overview of the most recent studies on this hyperthermophilic bacterium together with a critical discussion of the potential of fermentative production by this bacterium. The review article is organized into sections focused on biochemical, microbiological and technical issues, including the effect of substrate, reactor type, gas sparging, temperature, pH, hydraulic retention time and organic loading parameters on rate and yield of gas production.

Transparent YAG ceramics doped with active ions have become a valuable alternative to single crystals in solid state lasers in the last 10 years. The dopant ion substitutes Y3+ in the crystal, and despite low concentration it influences the sintering process. It has been shown for example that, differently to Yb, Nd fastens sintering, and this is related to the ionic radius. This work describes the influence of doping ions on the microstructure evolution of transparent YAG ceramics and on the material properties. Variously doped YAG ceramics have been prepared by solid state reaction under high vacuum and characterized in terms of microstructure and thermal and mechanical properties. A model relation approximating the optical transmittance is provided. Transmittance is then presented not only as a material characteristic, but also as an indicator of microstructure development. The sintering and densification is discussed in relation to the transmittance and to material properties, in all cases considering the effect of the doping ions. It is interesting to show the sensitivity of various properties on the microstructural homogeneity and the small differences in porosity lying between nearly dense, translucent and transparent material. The influence of the active ions on the sintering evolution and consequently final properties highlighted in the present work can be exploited for the optimization of the processing conditions.

The wetting of transparent YAG (Y3Al5O12) by alloys of the AgCuTi system has been studied for the first time. The role of the activity of Ti in determining the interactions between the brazing alloys and the YAG substrate has been analyzed by CALPHAD method. The low contact angle values ensure very good (at 950 °C) and fair (at 850 °C and 820 °C) wettability conditions. A significant reactivity occurred at the solid–liquid interfaces, with the formation of new phases. TiY2O5 was found at Ag–Ti/YAG interfaces, while a second layer, identified as “M4X”, associated to the significant wettability improvement, was specifically found only in the AgCuTi/YAG samples tested at 950 °C. All these phases were identified by the newly calculated Ag–Cu–Ti phase diagram and were confirmed by SEM and EDS analyses. The obtained good wettability and the maintained transparency of the YAG are promising for the production of brazed optical windows to be used under extreme conditions.

Increased levels of glucose uptake and increased expression of the glucose transporter (GLUT) genes are characteristic features of tumors. In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. In muscle tissues, glucose transport is primarily mediated by GLUT4. However, the mechanisms that regulate GLUT4 gene expression in tumor tissues are largely unknown. Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis. GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. PAX3/FKHR mutants with deletions in either the homeodomain (HD) or the FKHR-derived activation domain (FKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. Progressive 5-deletion analysis of GLUT4-P further identified a specific region of the promoter, 66/163 bp, which retained about 65% of the full transactivation effect. EMSA studies established that the PAX3/FKHR protein directly and specifically binds to this region and to a shorter fragment, 4/36 bp, that contains potential binding sites for HD and PD, but not to a 4/36-bp fragment whose HD and PD sites have been mutated. Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a 4/ 36-bp region within the GLUT4 promoter. Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro .( J Clin Endocrinol Metab 87: 5312–5324, 2002)

AlN, Si3N4 and SiAlON ceramic materials were sintered from sub-micrometre powders, by a hot pressing (HP) or pressureless sintering (PLS) procedures, at temperatures in the range of 1700-1850 degreesC. On these substrates, diamond coatings of different thickness were grown from a CH4/H-2 gas mixture, using a HF-CVD apparatus at 30 torr, 750 degreesC. Different pre-treatments of substrates, including chemical etching, diamond polishing and carbon seeding by pulsed laser deposition (PLD) of a graphite target, were used to study and enhance the first stages of diamond nucleation and growth. The structure and morphology of nitride ceramic substrates and diamond deposits have been characterised by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Diamond film quality and residual stress have been studied by Raman spectroscopy. The polycrystalline film adhesion on the various pre-treated ceramic nitride substrates has been evaluated by the indentation technique (Vickers' indenter). Morphological and structural configuration of polycrystalline diamond/ sintered ceramic nitride interfaces have been studied by SEM cross-sections.

Vasodilator actions of insulin are mediated by signaling pathways involving phosphatidylinositol 3-kinase (PI 3-kinase) and Akt that lead to activation of endothelial nitric oxide synthase (eNOS) in endothelium. Signaling molecules immediately upstream and downstream from PI 3-kinase involved with production of NO in response to insulin have not been previously identified. In this study, we evaluated roles of insulin receptor substrate 1 (IRS-1) and phosphoinositide-dependent kinase 1 (PDK-1) in production of NO. The fluorescent dye 4,5-diamine fluorescein diacetate was used to directly measure NO in NIH-3T3(IR) cells transiently cotransfected with eNOS and various IRS-1 or PDK-1 constructs. In control cells, transfected with only eNOS, insulin stimulated a rapid dose-dependent increase in NO. Overexpression of wild-type IRS-1 increased the maximal insulin response 3-fold. Overexpression of IRS1-F6 (mutant that does not bind PI 3-kinase) or an antisense ribozyme against IRS-1 substantially inhibited insulin-stimulated production of NO. Likewise, overexpression of wild-type PDK-1 enhanced insulin-stimulated production of NO, whereas a kinase-inactive mutant PDK-1 inhibited this action of insulin. Qualitatively similar results were observed in vascular endothelial cells. Production of NO by a calcium-dependent mechanism in response to lysophosphatidic acid was unaffected by either wild-type or mutant IRS-1 and PDK-1. We conclude that IRS-1 and PDK-1 play necessary roles in insulin-signaling pathways leading to activation of eNOS. Furthermore, classical Ca2+-mediated pathways for activation of eNOS are separable from IRS-1- and PDK-1-dependent insulin-signaling pathways.

The purpose of the current study was to examine the relationship between childhood abuse, social support, and problem-solving appraisal within a juvenile delinquent sample. Hierarchical regression analyses were used to assess whether childhood abuse, social support, and problem-solving appraisal were independently predictive of suicidality, and further, whether problem-solving appraisal and social support moderated the childhood abuse–suicidality relationship. Childhood sexual abuse was found to be an independent predictor of suicidal ideation and behavior. In addition, both problem-solving confidence and social support moderated the relationship between childhood abuse and suicidal ideation. The results of this study underscore the importance of both problem-solving appraisal and social support to suicidality in adolescents with a history of abuse.

The historical site of the Monte Mario lower Pleistocene succession (Rome, Italy) is an important marker of the Pliocene/Pleistocene boundary. Recently, the Monte Mario site was excavated and restudied. A spectacular angular unconformity characterizes the contact between the Monte Vaticano and the Monte Mario formations, which marks the Pliocene/Pleistocene boundary. Biostratigraphical analyses carried out on ostracod, foraminifer, and calcareous nannofossil assemblages indicate an Early Pliocene age (topmost Zanclean, 3.81–3.70 Ma) for the underlying Monte Vaticano Formation, whereas the Monte Mario Formation has been dated as early Pleistocene (Santernian, 1.66–1.59 Ma). Palaeomagnetic analyses point to C2Ar and C1r2r polarity chrons for the Monte Vaticano and the Monte Mario formations, respectively. The Monte Mario Formation consists of two obliquity-forced depositional sequences (MM1 and MM2) characterized by transgressive systems tracts of littoral marine environments at depths, respectively, of 40–80 m and 15–20 m. The data obtained from foraminifer and ostracod assemblages allow us to reconstruct early Pleistocene relative sea-level changes near Rome. At the Plio/Pleistocene transition, a relative sea-level drop of at least 260 m occurred, as a result of both tectonic uplift of the central Tyrrhenian margin and glacio-eustatic changes linked to early Pleistocene glaciation (Marine Isotope Stage 58).

Little is known about the distribution and species composition of cetaceans in the Gulf of Taranto, central Mediterranean Sea. Available information is limited to stranding reports and to scant preliminary observations at sea. Cetacean sightings were recorded between April 2007 and October 2009 during 23 daily boat surveys, totalling 1728 km of navigation. Three cetacean species were encountered: striped dolphins (n = 41), Risso's dolphins (n = 5) and fin whales (n = 3). An additional sighting of a sperm whale group is reported. Encounter rates of striped dolphins were the highest, suggesting a regular occurrence in the study area. Risso's dolphins seemed to be predictably present in continental slope waters off the coast of Basilicata. Fin whales and striped dolphins, normally inhabiting deep pelagic waters offshore, were found in continental slope waters relatively close to the coast, possibly due to the particular bathymetry of the Gulf of Taranto and to oceanographic conditions that enhance l...

The swine-origin influenza A (H1N1) virus is mainly responsible for flu. No hepatitis attributable to H1N1 virus has been previously documented. Herein, we report on a kidney transplant patient who developed influenza H1N1 virus-induced hepatocellular injury. The patient's body temperature was only somewhat elevated, and pulmonary and flu symptoms were mild. H1N1 virus was detected by polymerase chain reaction assay in nasopharyngeal and bronchoalveolar swabs, as well as in the serum. The hepatocellular injury episode resolved after the patient had been placed on oseltamivir therapy. This observation suggests that acute hepatocellular injury could be linked to the influenza H1N1 virus.

The aim of our study was to assess the use of orthodontic appliances made in titanium for patients with an allergy to resin and nickel. We aim to highlight the resolution of problems such as stomatitis and peri-labial dermatitis, which generally manifest in patients who use traditional orthodontic appliances in acrylic resin and steel.A total of 120 patients of ages between ten and fifteen undergoing orthodontic treatment requiring a rapid palatal expander or a mobile appliance were evaluated and two patch sensitivity tests were done to assess the presence of allergies.The biocompatibility of a material is directly dependent on its corrosion effect. If a metal does not allow the release of ions it will not have a damaging action or cause destruction on the cellular DNA. The oxidation status of an ion is related to the reactivity of the ion itself and thus may give the latter a carcinogenic effect. Titanium appliances used for this study have obtained excellent results due to their ability to form superficial oxides, which block the oxidation phenomenon and thus corrosion.We have noticed a total regression of the symptoms after the use of titanium appliances in patients who had a sensitivity reaction.

Aim of the present study was to present a case report of a patient suffering from pycnodysostosis and assess how it may manifest and affect the dental/ orthodontic treatment.An 11-year-old patient who was diagnosed with pycnodysostosis at the age of 18 months, attended the orthodontics department requiring treatment for extensive carious lesions, periodontal disease and severe crowding.After an accurate radiographic, clinical and orthodontic assessment of the patient taking into consideration the severity of the condition and the patient's necessities, we have formulated a treatment plan, which was accepted by both the patient and parents. We took into consideration the risks and benefits of the options available and the requests of the patient.We have decided to opt for the extraction of teeth to relieve the crowding as this was impeding good oral hygiene and hence increasing the risk of caries and periodontal disease. Such patients must be placed under an oral hygiene prevention scheme, a treatment plan must be accurately designed and the patient must be constantly motivated.

Immunosuppressant drugs (ISDs) are commonly prescribed to solid organ transplant patients. Their narrow therapeutic index and potential for toxicity necessitates careful monitoring of blood concentrations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods are increasingly used for ISD measurement. However, there remain many challenges with this methodology, particularly regarding interassay variability. The Thermo Scientific Prelude is an online extraction/liquid chromatography platform that uses turbulent flow technology coupled with MS/MS. A multicenter evaluation of the Prelude for the measurement of cyclosporine A, tacrolimus, and sirolimus is described. ISDs were measured at each site using standardized protocols. Sample preparation liquid chromatography-MS/MS was performed using the Prelude coupled to a TSQ Vantage. Chromatography was achieved with a Cyclone-P TurboFlow/Accucore C8 column combination using a multisolvent loading and eluting pump system. Mass spectrometry acquisitions were performed in selective reaction monitoring mode and data processed using TraceFinder (version 3.1). Multisite mean imprecision for cyclosporine A ranged from 8.8% (54 mcg/L) to 9.8% (450 mcg/L); for tacrolimus, 4.7% (15.5 mcg/L) to 12.6% (2.5 mcg/L); for sirolimus, 7.4% (19.9 mcg/L) to 16.5% (2.6 mcg/L). Approximately 110 specimens were used for method comparison. For cyclosporine A, mean bias against the multisite mean ranged from -18% to 1%; for tacrolimus, values ranged from -7% to 4%; for sirolimus, values ranged from -4% to 2%. Comparisons of multisite mean Prelude results with routine ISD method results was also performed for cyclosporine A (slope = 0.7878, intercept = 24.16, r = 0.98), tacrolimus (slope = 0.9391, intercept = 0.1017, r = 98), and sirolimus (slope = 0.9618, intercept = 0.1483, r = 0.97). The Prelude ISD method offers acceptable and comparable multisite performance. This study has also highlighted the importance of adopting standardized protocols and LC-MS/MS methods for better comparability between ISD assays.

To examine contributions of specific YXXM motifs in human insulin receptor substrate-1 (IRS-1) to mediating the metabolic actions of insulin, we studied IRS-1 mutants containing various substitutions of Phe for Tyr. In transfected NIH-3T3(IR) cells, insulin stimulation caused a 5-fold increase in phosphatidylinositol 3-kinase (PI3K) activity coimmunoprecipitated with wild-type IRS-1. No PI3K activity was associated with IRS1-F6 (Phe substituted for Tyr at positions 465, 612, 632, 662, 941, and 989). Adding back both Tyr(612) and Tyr(632) fully restored IRS-1-associated PI3K activity, whereas adding back either Tyr(612) or Tyr(632) alone was associated with intermediate PI3K activity. In rat adipose cells transfected with epitope-tagged GLUT4, insulin stimulation caused a 2-fold increase in cell surface GLUT4-HA. Cotransfection of cells with GLUT4-HA and either wild-type IRS-1 or IRS1-Y612/Y632 increased basal cell surface GLUT4-HA (in the absence of insulin) to approximately 80% of the levels seen in insulin-stimulated control cells, whereas overexpression of IRS1-F6 had no effect on the insulin dose-response curve. Overexpression of IRS1-Y612 or IRS1-Y632 caused intermediate effects. Thus, both Tyr(612) and Tyr(632) are important for IRS-1 to fully activate PI3K and mediate translocation of GLUT4 in response to insulin.

Protective coatings for non-oxide ceramics have a great potential for reducing oxidation under hot oxidising conditions. In the present paper a technique to coat silicon nitride and silicon carbide ceramics with a glass layer is proposed. The composition of the coating is in the Al2O3–SiO2–Y2O3 system and is close to the composition of the grain boundary phase of the two dense materials. At the processing temperature, that was slightly higher than the glass softening temperature, the glass coating wet both Si3 N4 and SiC and promoted strong adhesion with the ceramic without the formation of any new weak compounds. The coatings are different for Si3 N4 and SiC based systems, especially across the original ceramic/glass interface. In the case of silicon nitride, the grains at the interface that were in direct contact with the glass dissolved until the glass became saturated with nitrogen. Then the Si3 N4 grains moved from their original position towards the free glass surface. The extent of dissolut...

Insulin evokes diverse biological effects through receptor-mediated tyrosine phosphorylation of the insulin receptor substrate (IRS) proteins. Here, we show that, in vitro, the IRS-1, -2 and -3 pleckstrin homology (PH) domains bind with different specificities to the 3-phosphorylated phosphoinositides. In fact, the IRS-1 PH domain binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdIns-3,4,5-P3), the IRS-2 PH domain to phosphatidylinositol 3,4-bisphosphate (PtdIns-3,4-P2), and the IRS-3 PH domain to phosphatidylinositol 3-phosphate. When expressed in NIH-IR fibroblasts and L6 myocytes, the IRS-1 and -2 PH domains tagged with green fluorescent protein (GFP) are localized exclusively in the cytoplasm. Stimulation with insulin causes a translocation of the GFP-IRS-1 and -2 PH domains to the plasma membrane within 3-5 min. This translocation is blocked by the phosphatidylinositol 3-kinase (PI 3-K) inhibitors, wortmannin and LY294002, suggesting that this event is PI 3-K dependent. Interestingly, platelet-derived growth factor (PDGF) did not induce translocation of the IRS-1 and -2 PH domains to the plasma membrane, indicating the existence of specificity for insulin. In contrast, the GFP-IRS-3 PH domain is constitutively localized to the plasma membrane. These results reveal a differential regulation of the IRS PH domains and a novel positive feedback loop in which PI 3-K functions as both an upstream regulator and a downstream effector of IRS-1 and -2 signaling.

Las caracteristicas de la propia superficie de los azulejos ceramicos esmaltados tiene una influencia considerable en la respuesta mecanica de estos a las distintas tensiones provenientes del entorno. De acuerdo con esto, uno de los parametros mas importantes que definen la correcta utilizacion de estos productos es el comportamiento ante el desgaste de la propia superficie. Debido a que la capa de esmalte es la conexion fisica entre el entorno y el cuerpo ceramico, sus caracteristicas tambien determinan vida util del azulejo. El objetivo de la investigacion de la que damos cuenta aqui fue calcular la influencia de la dureza, resistencia a la fractura y porosidad de la capa de esmalte en el comportamiento ante el desgaste de la propia superficie de los azulejos ceramicos esmaltados. Los resultados obtenidos muestran una clara relacion entre las caracteristicas de la capa de esmalte y la eliminacion del material en forma de perdida de peso normalizada, que puede ser considerada como una herramienta util para predecir el comportamiento ante el desgaste de estos productos.

La sottrazione di rifiuti alla discarica e la loro valorizzazione economica sono attività che riguardano la tutela dell’Ambiente, la salute della popolazione e lo sviluppo industriale di un Paese, in particolare se povero di materie prime. Il Progetto LITCAR ha visto la partecipazione di vari laboratori presenti in Regione, con competenze specifiche e diversificate, che hanno contribuito alla realizzazione di un obiettivo condiviso: la valorizzazione dei rifiuti come materia prima secondaria per la realizzazione di prodotti commerciali a ridotto impatto ambientale, in linea con la filosofia europea della Politica Integrata di Prodotto (IPP). La suddivisione dei compiti, la condivisione di informazioni all’interno del gruppo di lavoro e la collaborazione di aziende che hanno creduto nel progetto, hanno consentito l’ottenimento di prodotti per l’edilizia ad elevate prestazioni tecnologiche.

This special issue examines, from a historical and contemporary perspective, notions of free speech and religious freedom within non-Muslim and Muslim societies and the ways in which these interact...

Research which has related scores on the Children's Depression Inventory (CDI) to suicidality have generally neglected to examine the possibility that specific depressive factors within the CDI may be more predictive of suicidality than the full scale score. Knowledge of such factors would help to explain the relationship between depression and suicidality and improve the prediction of suicidal behavior. The current study examined the relationship of depressive factors to suicidality in a sample of 200 incarcerated juvenile delinquents. The published factor structure for the CDI and one derived from the delinquent population were compared. Results revealed two factors from the derived solution, hopelessness and low self-esteem, to be more powerful predictors of suicidal ideation than the full-scale CDI score. These results suggest that symptoms such as low self-esteem and hopelessness may be responsible for the well-documented relationship between depression and suicidality. Furthermore, it appears that the prediction of suicidality may be improved by examining specific depressive factors in suicide research as opposed to full-scale scores from depression inventories such as the CDI.

In 1992, the defmition of erectile dysfunction (ED) replaced the old term of impotence that had been used for many centuries, in order to avoid the general confusion existing until today in this field. In the past, the origin of impotence had been attributed to different causes such as psychological diseases, or witches and demons. In 1764, Fusanacci described impotence that can occur in the male as well as in the female, as a defect in reproduction. The main causes responsible for impotence were identified as inability to achieve erection, a very fluid seminal ejaculation, a defective organ, dryness of testicles, and lack of copulative power after many sexual intercourses with healthy women. Some decades later in 1847, Beatty affirmed that one of the most remarkable changes that can be observed in the passage from childhood to maturity is the development of the sexual organs, followed by the appearanee of new sensations. He dis1inguished impotenee that oeeurs only in men from sterility that for him affeets women, and divided the eauses of impotenee into 3 classes: organie, functional and moral (today defmed as psyehologieal). For Beatty, the . progress of knowledge had taken away magie and soreery from the human mind and now it was widespread only ," among the lowest and most ignorant classes of humble people. In this way, he shows the evolution ofmedieal scienee d~ in XIX eentury in aceepting only the rational explanation of the human diseases.

In recent years, titanium dioxide has been extensively applied in several fields, in fact it has been used in pigments, in gas sensors, in cosmetic products, in dielectric materials and for photocatalysis. In particular, as photocatalyst, its semiconductor characteristics allow its utilization to detoxify some recalcitrant environmental pollutants. Indeed, titania has other positive characteristics such as nontoxicity, long term stability and low cost. In the present work, the photocatalytic activity of ceramic products containing anatase has been evaluated. Commercial anatase powders were added to different ceramic body mixes. Pressed pellets were fired at different temperatures. The ceramic products were analysed by X-ray diffraction analysis to determine the mineralogical compositions, in particular to detect the polymorphic form in which titania was present. The photocatalytic activity of the prepared specimen was then evaluated in order to assess the potentiality of these innovative materials in getting some attractive and favourable side-effects. Actually, under UVA irradiation, ceramics containing titania might be able to attain some degree of sterilization, self cleaning and pollutant removal, whose extent mainly depends on the processing conditions.

We assessed whether conversion from tacrolimus (TAC) to cyclosporine (CsA) was associated with a reduction in hepatitis C virus (HCV) viral load among HCV-positive liver transplant (OLT) patients. Patients and Methods Nine OLT patients with recurrent HCV have TAC and prednisone immunosuppression. None received any HCV antiviral therapy. After the last intake of TAC, the patients underwent a 12-hour area under the curve (AUC 12 ) measurement of both TAC and HCV viral loads. The next morning (D 0 ) patients were given CsA (4 mg/kg bid). At the first intake of CsA and at 1 month (M 1 ) later, the patients underwent AUC 12 for CsA and HCV viral loads. Biological data, including aspartate (AST) and alanine (ALT) aminotransferase, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), and bilirubin levels, were collected during AUC 12 , and at M 1 and M 3 . Results With respect to liver enzymes (AST, ALT, GGT), there was no significant difference between D 0 , M 1 , and M 3 . Conversely, there was a significant decrease in AP between D 0 and M 3 ( P = .02), and a significant increase in total bilirubin between D 0 and M 1 ( P = .04), and between D 0 and M 3 ( P = .01). HCV viral load significantly increased by M 3 ( P = .01). At no time (D 0 , M 1 ) was there any correlation between the AUC 12 of TAC or CsA, and between AUC 12 HCV viral load. Conclusion This pilot study found no acute or chronic anti-HCV effects from CsA that were evident within 12 hours after CsA administrations or beyond 1 month of CsA therapy, respectively.

To optimize the labeling and visualization of PCR products we tested different variables, including deoxynucleotide concentration and ratio, dilution of labeled product, number of PCR cycles, and use of one-step or nested labeling protocols. Labeling was achieved using a fixed amount of labeled dATP, whose relative specific activity was varied by adding increasing amounts of cold dATP. Optimal PCR-labeling intensity was reached at dATP concentrations between 0.9 and 7.0 μmol/L, with a peak at 1.8 μmol/L. This concentration corresponded to an optimal ratio between the increase in specific activity and the decrease in DNA yield. Nucleotide imbalances >1:2 were not advantageous. Mutational analysis by single-strand conformational polymorphism (SSCP) was used to validate PCR-labeling protocols. The limiting nucleotide concentrations did not affect SSCP. Clear SSCP patterns were obtained using DNA templates of different sizes derived from several genes. SSCP patterns obtained using one-step or nested PCR-labeling protocols were equivalent and were visualized after overnight exposure, using [α35S]dATP as the label. Dilutions of labeled products ranging between 1:10 and 1:2.5 influenced SSCP patterns, and the lowest dilution tested produced better-defined and more-intense signals. Optimized SSCP conditions allowed the detection of novel and previously characterized nucleotide variants. Clear microsatellite typing was also obtained using optimized protocols and [α35S]dATP as the label.

This paper describes the characteristics of pumice soils from the area of Mount Vesuvius and discusses sinking, watering and other geotechnical tests on pumice from a number of sites. Attention is drawn to the presence of both inter- and intra-particle voids within this material and appropriate modifications to the standard solid-water-air phase diagram are suggested to take account of this. The importance of understanding the structure of the pumice and its response to rainfall/ground water conditions is discussed in relation to both landslips and stabilisation works.

Germline mutations of the hMLH1 gene are estimated to account for a large fraction of kindreds affected by hereditary non-polyposis colorectal cancer (HNPCC). In a significant number of cases, hMLH1 mutations result in the expression of truncated proteins. We report here two novel alternatively spliced forms of hMLH1 mRNA in normal lymphocytes. One of these novel isoforms lacks the coding region of the gene between codons 557 and 578, corresponding to the entire exon 15. The deletion introduces a frameshift that results in a premature stop signal. The other isoform is characterised by an in-frame deletion spanning codons 578-632, corresponding to loss of the entire exon 16. Further studies are necessary to establish the biological significance of these alternative splicings. The presence of alternatively spliced hMLH1 transcripts that mimic pathogenic mutations should be taken into account in the mutational screening of the hMLH1 gene by reverse transcription-polymerase chain reaction methodologies.