Brain stimulation in obesity Göbel, C H; Tronnier, V M; Münte, T F
International journal of obesity (2005),
12/2017, Letnik:
41, Številka:
12
Journal Article
Recenzirano
Obesity is taking up epidemic proportions worldwide with significant impacts on the health of both the affected individual and on society as a whole. Treatment approaches consist of behavioural and ...pharmacological approaches, however, these are often found to be ineffective. In severe obesity, bariatric surgery is frequently performed. Unfortunately, 40% of patients show substantial weight gain over the long term or display the associated metabolic syndrome, making the development of novel therapies necessary. This review summarizes some of the current conceptual models, in particularly the 'food addiction' model, and then discusses specific therapeutic targets of brain stimulation, both non-invasive (transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and transcutaneous vagus nerve stimulation (VNS)) and invasive (deep brain stimulation and invasive VNS). As we will show, neuromodulatory approaches represent a promising tool for targeting specific brain structures implicated in the pathophysiology of obesity. Non-invasive techniques such as TMS, tDCS and transcutaneous VNS need further investigation before they may become ready for clinical usage. The currently available study data suggest that deep brain stimulation may become an effective and acceptable therapy for otherwise treatment-resistant obese patients. The results of the currently undergoing clinical trials are eagerly awaited.
Thin films of nominally pure and 10 mol % Gd-doped ceria were grown on Al2O3⟨11̅02⟩ (r-cut) and MgO⟨100⟩ substrates with pulsed laser deposition (PLD). Their electrical conductivity properties were ...measured using impedance spectroscopy. Oxygen partial pressure and temperature dependence indicate that the nominally pure films are contaminated with acceptor impurities whose concentration is found to vary perceptibly among the samples. Quite remarkably, the nanocrystalline 10 mol % Gd-doped thin films show conductivities that are, as expected, lower than those for epitaxial films but surprisingly much larger than those obtained previously from other comparable nanocrystalline films (e.g., grown on SiO2), indicating that the oxygen vacancies are much less depleted at the grain boundaries. Correspondingly, the space charge potential was found to be unusually small with a value of 0.19 ± 0.05 V.
The efficacy of immune surveillance and antigen-specific cancer immunotherapy equally depends on the activation of a sustained immune response targeting cancer antigens and the susceptibility of ...cancer cells to immune effector mechanisms. Using functional expression cloning and T-cell receptor (TCR) transgenic mice, we have identified cyclooxygenase 2/prostaglandin-endoperoxide synthase 2 (COX-2) as resistance factor against the cytotoxicity induced by activated, antigen-specific T cells. Expressing COX-2, but not a catalytically inactive COX-2 mutant, increased the clonogenic survival of E1A-transformed murine cancer cells when cocultured with lymphocytes from St42Rag2(-/-) mice harboring a transgenic TCR directed against an E1A epitope. COX-2 expressing tumors established in immune-deficient mice were less susceptible to adoptive immunotherapy with TCR transgenic lymphocytes in vivo. Also, immune surveillance of COX-2-positive tumor cells in TCR transgenic mice was less efficient. The growth of murine MC-GP tumors, which show high endogenous COX-2 expression, in immunocompetent mice was effectively suppressed by treatment with a selective COX-2 inhibitor, celecoxib. Mechanistically, COX-2 expression blunted the interferon-gamma release of antigen-specific T cells exposed to their respective cellular targets, and increased the expression of interleukin-4 and indoleamine 2,3-dioxygenase by tumor cells. Addition of interferon-gamma sensitized COX-2 expressing cancer cells to tumor suppression by antigen-specific T cells. In conclusion, COX-2, which is frequently induced in colorectal cancer, contributes to immune evasion and resistance to antigen-specific cancer immunotherapy by local suppression of T-cell effector functions.
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•Silica support material during catalyst preparation has a strong influence on the performance of the MnxOy-Na2WO4/SiO2 for the OCM.•SBA-15 has been confirmed as an optimum silica ...support material for the MnxOy-Na2WO4.•Under reaction conditions, structural changes in silica support material occurred for comprehensively investigated MnxOy-Na2WO4/SiO2 catalysts and MnWO4 phase was detected.•α-Cristobalite phase of the SiO2 is less stable for the low-performance catalyst Cat-L under reaction conditions.•The transformation of amorphous silica to α-cristobalite starts at lower temperature for the high-performance catalyst Cat-H.
The oxidative coupling of methane (OCM) is one of the best methods for the direct conversion of methane. Among the known OCM catalysts, MnxOy-Na2WO4/SiO2 is a promising candidate for an industrial application, showing a high methane conversion and C2 selectivity, with a good stability during long-term catalytic activity tests. In the present study, some results have been already published and discussed briefly in our previous short communication. However, we herein investigated comprehensively the influence of various silica support materials on the performance of the MnxOy-Na2WO4/SiO2 system in the OCM by means of ex situ and in situ XRD, BET, SEM and TEM characterization methods and showed new results to reveal possible support effects on the catalyst. The catalytic performance of most MnxOy-Na2WO4/SiO2 catalysts supported by different silica support materials did not differ substantially. However, the performance of the SBA-15 supported catalyst was outstanding and the methane conversion was nearly twofold higher in comparison to the other silica supported catalysts at similar C2 selectivity as shown before in the communication. The reason of this substantial increase in performance could be the ordered mesoporous structure of the SBA-15 support material, homogeneous dispersion of active components and high number of active sites responsible for the OCM.
We previously reported that patatin-like protein 2 (PLP2), a pathogen-induced patatin-like lipid acyl hydrolase, promotes cell death and negatively affects Arabidopsis resistance to the fungus ...Botrytis cinerea and to the bacteria Pseudomonas syringae. We show here that, on the contrary, PLP2 contributes to resistance to Cucumber mosaic virus, an obligate parasite inducing the hypersensitive response. These contrasted impacts on different pathosystems were also reflected by differential effects on defense gene induction. To examine a possible link between PLP2 lipolytic activity and oxylipin metabolism, gene expression profiling was performed and identified B. cinerea among these pathogens as the strongest inducer of most oxylipin biosynthetic genes. Quantitative oxylipin profiling in wild-type and PLP2-modified, Botrytis-challenged plants established the massive accumulation of oxidized fatty acid derivatives in infected leaves. Several compounds previously described as modulating plant tissue damage and issued from the α-dioxygenase pathway were found to accumulate in a PLP2-dependent manner. Finally, the contribution of PLP2 to genetically controlled cell death was evaluated using PLP2-silenced or -overexpressing plants crossed with the lesion mimic mutant vascular-associated death 1 (vad1). Phenotypic analysis of double-mutant progeny showed that PLP2 expression strongly promotes necrotic symptoms in vad1 leaves. Collectively, our data indicate that PLP2 is an integral component of the plant cell death execution machinery, possibly providing fatty acid precursors for the biosynthesis of specific oxylipins and differentially affecting resistance to pathogens with distinct lifestyles.
Maintaining pace with ongoing changes due to digitalization is challenging for manufacturing companies. For successful implementation of digitalization, manufacturing companies must consider their ...existing technical systems, organizational structures, and processes, as well as social aspects. With the support of a maturity model, a company-specific digitalization level can be evaluated to provide manufacturing companies with an initial insight into their particular status quo; this can serve as a starting point for future optimization and digitalization projects. Furthermore, the results of such an analysis allow objective comparison of different areas within the company and with competitors. In this paper, the “Integrierte Arbeitssystemgestaltung in digitalisierten Produktionsunternehmen” (InAsPro) maturity model is presented, which considers the
Development
,
Production
, and
Assembly
product lifecycle phases, as well as
Aftersales
, and assesses their digitalization level focusing on the four dimensions of
Technology
,
Organization
,
Social Issues
, and
Corporate Strategy
. The maturity model’s rating scale distinguishes between four maturity levels. The results given by the InAsPro maturity model for an entire company are presented, along with those for each product lifecycle phase. Extensive descriptions for each specific maturity level are also provided.
Thin films of 2mol% Nb-doped cerium oxide are prepared via pulsed laser deposition and investigated using impedance spectroscopy. The electronic conductivity of various films having different ...microstructures is found to decrease with increasing grain boundary density. The defect chemistry is treated in terms of anti-Frenkel disorder, and possible origins of the blocking effect of the grain boundaries are discussed.
► Epitaxial and nanocrystalline donor-doped ceria films are investigated. ► The conductivity is lower in the nanocrystalline films than in the epitaxial films. ► The grain boundaries block the electronic conductivity. ► Both mobility as well as space charge effects can explain the lower GB conductivity.
Single enantiomers of R/S-methylbenzylamine (MBA) were found to selectively form adducts with two chiral Cu–salen complexes, CuII(1) (H2 1 = ...N,N′-bis(3,5-ditert-butylsalicylidene)-1,2-diaminocyclohexane) and CuII(2) (H2 2 = N,N′-bis-salicylidene-1,2-cyclohexanediamino). The axial g/A spin Hamiltonian parameters of the Cu–MBA adducts were typical of 5-coordinate species. Enantiomer discrimination in the MBA binding was directly evidenced by W-band CW EPR, revealing an 86 ± 5% preference for formation of the R,R-Cu(1) + S-MBA adducts compared to R,R-Cu(1) + R-MBA; this was reduced to a 57 ± 5% preference for R,R-Cu(2) + S-MBA following removal of the tert-butyl groups. The structure of these diastereomeric adducts was further probed by different hyperfine techniques (ENDOR and HYSCORE), although no structural differences were detected between these adducts using these techniques. The diastereomeric adducts were found to possess lower symmetry, as evidenced by rhombic g tensors and inequivalent Himine couplings. This was caused by the selective binding mode of MBA onto one side of the chiral CuII complex. DFT calculations were performed on the R,R-Cu(1) + S-MBA and R,R-Cu(1) + R-MBA adducts. A distinct difference in orientation and binding mode of the MBA was identified in both adducts, confirming the experimental results. The preferred heterochiral R,R-Cu(1) + S-MBA adduct was found to be 5 kJ mol–1 lower in energy compared to the homochiral adduct. A delicate balance of steric repulsion between the α-proton (attached to the asymmetric carbon atom) of MBA and the methine proton (attached to the asymmetric carbon atom) of Cu(1) was crucial in the stereoselective binding.
Background and aims: The diagnostic yield of capsule endoscopy (CE) compared with magnetic resonance imaging (MRI) in small bowel Crohn’s disease is not well established. We prospectively ...investigated CE, MRI, and double contrast fluoroscopy in patients with suspected small bowel Crohn’s disease. Methods: Fifty two consecutive patients (39 females, 13 males) were investigated by MRI, fluoroscopy and—if bowel obstruction could be excluded—by CE. In 25, Crohn’s disease was newly suspected while the diagnosis of Crohn’s disease (non-small bowel) had been previously established in 27. Results: Small bowel Crohn’s disease was diagnosed in 41 of 52 patients (79%). CE was not accomplished in 14 patients due to bowel strictures. Of the remaining 27 patients, CE, MRI, and fluoroscopy detected small bowel Crohn’s disease in 25 (93%), 21 (78%), and 7 (of 21; 33%) cases, respectively. CE was the only diagnostic tool in four patients. CE was slightly more sensitive than MRI (12 v 10 of 13 in suspected Crohn’s disease and 13 v 11 of 14 in established Crohn’s disease). MRI detected inflammatory conglomerates and enteric fistulae in three and two cases, respectively. Conclusion: CE and MRI are complementary methods for diagnosing small bowel Crohn’s disease. CE is capable of detecting limited mucosal lesions that may be missed by MRI, but awareness of bowel obstruction is mandatory. In contrast, MRI is helpful in identifying transmural Crohn’s disease and extraluminal lesions, and may exclude strictures.
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