München, Technische Universität München, Diss., 2014
München, Technische Universität München, Diss., 2014
Munich, Technical University of Munich, Diss., 2014
We have developed a comprehensive strategy for quantitatively assessing the hydrophilicity/hydrophobicity of nanoporous materials by combining advanced adsorption studies, novel liquid intrusion ...techniques, and solid-state NMR spectroscopy. For this, we have chosen a well-defined system of model materials, i.e., the highly ordered mesoporous silica molecular sieve SBA-15 in its pristine state and functionalized with different amounts of trimethylsilyl (TMS) groups, allowing one to accurately tailor the surface chemistry while maintaining the well-defined pore structure. For an absolute quantification of the trimethylsilyl group density, quantitative 1H solid-state NMR spectroscopy under magic angle spinning was employed. A full textural characterization of the materials was obtained by high-resolution argon 87 K adsorption, coupled with the application of dedicated methods based on nonlocal-density functional theory (NLDFT). Based on the known texture of the model materials, we developed a novel methodology allowing one to determine the effective contact angle of water adsorbed on the pore surfaces from complete wetting to nonwetting, constituting a powerful parameter for the characterization of the surface chemistry inside porous materials. The surface chemistry was found to vary from hydrophilic to hydrophobic as the TMS functionalization content was increased. For wetting and partially wetting surfaces, pore condensation of water is observed at pressures P smaller than the bulk saturation pressure p 0 (i.e., at p/p 0 < 1) and the effective contact angle of water on the pore walls could be derived from the water sorption isotherms. However, for nonwetting surfaces, pore condensation occurs at pressures above the saturation pressure (i.e., at p/p 0 > 1). In this case, we investigated the pore filling of water (i.e., the vapor–liquid phase transition) by the application of a novel, liquid water intrusion/extrusion methodology, allowing one to derive the effective contact angle of water on the pore walls even in the case of nonwetting. Complementary molecular simulations provide density profiles of water on pristine and TMS-grafted silica surfaces (mimicking the tailored, functionalized experimental silica surfaces), which allow for a molecular view on the water adsorbate structure. Summarizing, we present a comprehensive and reliable methodology for quantitatively assessing the hydrophilicity/hydrophobicity of siliceous nanoporous materials, which has the potential to optimize applications in heterogeneous catalysis and separation (e.g., chromatography).
In renal transplantation, complement is involved in ischemia reperfusion injury, graft rejection and dysfunction. However, it is still unclear how induction of complement and its activation are ...initiated. Using allograft biopsies of a well-characterized cohort of 28 renal transplant patients with no rejection (Ctrl), delayed graft function (DGF), acute T-cell-mediated (TCMR) or antibody-mediated rejection (ABMR) we analyzed differences in complement reaction. For that mRNA was isolated from FFPE sections, quantified with a multiplex gene expression panel and correlated with transplant conditions and follow-up of patients. Additionally, inflammatory cells were quantified by multiplex immunohistochemistry. In allograft biopsies with TCMR and ABMR gene expression of C1QB was 2-4 fold elevated compared to Ctrl. In TCMR biopsies, mRNA counts of several complement-related genes including C1S, C3, CFB and complement regulators CFH, CR1 and SERPING1 were significantly increased compared to Ctrl. Interestingly, expression levels of about 75% of the analyzed complement related genes correlated with cold ischemia time (CIT) and markers of inflammation. In conclusion, this study suggest an important role of complement in transplant pathology which seems to be at least in part triggered by CIT. Multiplex mRNA analysis might be a useful method to refine diagnosis and explore new pathways involved in rejection.
Hair cells detect sound and movement and transmit this information via specialized ribbon synapses. Here we report that asteroid, a gene identified in an ethylnitrosourea mutagenesis screen of ...zebrafish larvae for auditory/vestibular mutants, encodes vesicular glutamate transporter 3 (Vglut3). A splice site mutation in exon 2 of vglut3 results in a severe truncation of the predicted protein product and morpholinos directed against the vglut3 ATG start site or the affected splice junction replicate the asteroid phenotype. In situ hybridization shows that vglut3 is exclusively expressed in hair cells of the ear and lateral line organ. A second transporter gene, vglut1, is also expressed in zebrafish hair cells, but the level of vglut1 mRNA is not increased in the absence of Vglut3. Antibodies against Vglut3 label the basal end of hair cells and labeling is not present in asteroid/vglut3 mutants. Based on the localization of Vglut3 in hair cells, we suspected that the lack of vestibulo-ocular and acoustic startle reflexes in asteroid/vglut3 mutants was attributable to a defect in synaptic transmission in hair cells. In support of this notion, action currents in postsynaptic acousticolateralis neurons are absent in asteroid/vglut3 mutants. At the ultrastructural level, mutant asteroid/vglut3 hair cells show a decrease in the number of ribbon-associated synaptic vesicles, indicating a role for Vglut3 in synaptic vesicle biogenesis and/or tethering to the ribbon body. Lack of postsynaptic action currents in the mutants suggests that the remaining hair-cell synaptic vesicles contain insufficient levels of glutamate for generation of action potentials in first-order neurons.
Since there is sound evidence that communication skills training (CST) programs modify communication behavior of oncology clinicians, they have been widely implemented over the last decades. However, ...more recently, certain aspects of this training have been criticized.
Based on this background, a call to re-launch a discussion about the future of CST led to the third European consensus meeting on communication in cancer care, organized by the Swiss Cancer League. During this meeting, which brought together European experts in the field of clinical communication and training of communication in the oncology setting, oncology clinicians, representatives of the European Society of Medical Oncology and a member of the European Oncology Nursing Society, the recommendations of the second European consensus meeting were updated and expanded.
The expanded recommendations recall the guiding principles of communication in cancer care, underline the important role of clinician’s self-awareness, and of relational and contextual factors in clinical communication, and provide direction for the further development of communication training.
This third European consensus meeting defines key elements for the development of a next generation of communication training for oncology clinicians.
Rationale
Due to the spatial heterogeneity of stable isotope ratios of single elements measured in attempts to georeference bioarchaeological finds, multi‐isotope fingerprints are frequently employed ...under the assumption that similar isotopic signatures are indicative of similar shared environments by the individuals studied. The extraction of the spatial information from multi‐isotope datasets, however, is challenging.
Methods
Gaussian mixture clustering of six‐ to seven‐dimensional isotopic fingerprints measured in archaeological animal and human bones was performed. Uncremated animal bones served for an isotopic mapping of a specific reference area of eminent archaeological importance, namely the Inn‐Eisack‐Adige passage across the European Alps. The fingerprints consist of 87Sr/86Sr, 208Pb/204Pb, 207Pb/204Pb, 206Pb/204Pb, 208Pb/207Pb, and 206Pb/207Pb ratios, and δ18Ophosphate values in uncremated bone apatite, while the thermally unstable δ18O values of human cremations from this region were discarded.
Results
The bone finds were successfully decontaminated. Animal and human isotope clusters not only reflect individual similarities in the multi‐isotopic fingerprints, but also permit a spatial allocation of the finds. This holds also for cremated finds where the δ18Ophosphate value is no longer informative. To our knowledge, for the first time Pb stable isotopes have been systematically studied in cremated skeletal remains and proved significant in a region that was sought after for its ore deposits in prehistory.
Conclusions
Gaussian mixture clustering is a promising method for the interpretation of multi‐isotopic fingerprints aiming at detecting and quantifying migration and trade.
Nanoporous silica is widely used as a support material for chemically bound stationary phases in chromatographic separations as well as for catalytic applications. Tuning of textural properties and ...surface chemistry of stationary phase materials (SPMs) is crucial to enhance their selectivity to certain compounds and the resulting process efficiency. Nanoporous silica supports are beneficial, as surface modifications are possible with a large variety of hydrophilic and hydrophobic functional groups, but their influence on the surface properties has not been evaluated in detail. In this sense, the contact angle is a key parameter for the assessment of surface chemistry, but its quantification in pores is challenging and requires a combination of various experimental techniques. This work demonstrates that combining water adsorption and intrusion measurements allows for the determination of the effective contact angle of adsorbed water on the pore walls for wetting, partial wetting, and nonwetting situations using functionalized hydrophilic and hydrophobic silica SPMs as model materials. Furthermore, NMR relaxometry experiments reveal that the ratio of the spin–lattice (T 1) to spin–spin (T 2) relaxation time of the adsorbed water film (T 1,ads.film/T 2,ads.film ratio) can be correlated with the effective adsorption strength of water on the surface. Indeed, a linear correlation between the negative inverse relaxation time ratio (−T 2,ads.film/T 1,ads.film) and the contact angle is observed. Our work demonstrates that water vapor adsorption and water intrusion experiments coupled with NMR relaxometry can be used as complementary tools to quantify the wettability and surface chemistry of nanoporous materials. This approach allows for addressing important aspects of nanoscale wettability in the context of material synthesis as well as for their application in chromatographic separation processes and catalysis.
Depression predicts adverse prognosis in patients with coronary artery disease (CAD), but previous treatment trials yielded mixed results. We tested the hypothesis that stepwise psychotherapy ...improves depressive symptoms more than simple information.
In a multicenter trial, we randomized 570 CAD patients scoring higher than 7 on the Hospital Anxiety and Depression Scale-depression subscale to usual care plus either one information session (UC-IS) or stepwise psychotherapy (UC-PT). UC-PT patients received three individual psychotherapy sessions. Those still depressed were offered group psychotherapy (25 sessions). The primary outcome was changed in the Hospital Anxiety and Depression Scale-depression scores from baseline to 18 months. Preplanned subgroup analyses examined whether treatment responses differed by patients' sex and personality factors (Type D).
The mean (standard deviation) depression scores declined from 10.4 (2.5) to 8.7 (4.1) at 18 months in UC-PT and from 10.4 (2.5) to 8.9 (3.9) in UC-IS (both p < .001). There was no significant group difference in change of depressive symptoms (group-by-time effect, p = .90). Preplanned subgroup analyses revealed no differences in treatment effects between men versus women (ptreatment-by-sex interaction = .799) but a significant treatment-by-Type D interaction on change in depressive symptoms (p = .026) with a trend for stronger improvement with UC-PT than UC-IS in Type D patients (n = 341, p = .057) and no such difference in improvement in patients without Type D (n = 227, p = .54).
Stepwise psychotherapy failed to improve depressive symptoms in CAD patients more than UC-IS. The intervention might be beneficial for depressed CAD patients with Type D personality. However, this finding requires further study.
www.clinicaltrials.gov NCT00705965; www.isrctn.com ISRCTN76240576.
Zero-time biopsies are taken to determine the quality of the donor organ at the time of transplantation. Histological analyses alone have so far not been able to identify parameters that allow the ...prediction of subsequent rejection episodes or graft survival. This study investigated whether gene expression analyses of zero-time biopsies might support this prediction. Using a well-characterized cohort of 26 zero-time biopsies from renal transplant patients that include 4 living donor (LD) and 22 deceased donor (DD) biopsies that later developed no rejection (Ctrl,
= 7), delayed graft function (DGF,
= 4), cellular (T-cell mediated rejection; TCMR,
= 8), or antibody-mediated rejection (ABMR,
= 7), we analyzed gene expression profiles for different types of subsequent renal transplant complication. To this end, RNA was isolated from formalin-fixed, paraffin-embedded (FFPE) sections and gene expression profiles were quantified. Results were correlated with transplant data and B-cell, and plasma cell infiltration was assessed by immunofluorescence microscopy. Both principal component analysis and clustering analysis of gene expression data revealed marked separation between LDs and DDs. Differential expression analysis identified 185 significant differentially expressed genes (adjusted
< 0.05). The expression of 68% of these genes significantly correlated with cold ischemia time (CIT). Furthermore, immunoglobulins were differentially expressed in zero-time biopsies from transplants later developing rejection (TCMR + ABMR) compared to non-rejected (Ctrl + DGF) transplants. In addition, immunoglobulin expression did not correlate with CIT but was increased in transplants with previous acute renal failure (ARF). In conclusion, gene expression profiles in zero-time biopsies derived from LDs are markedly different from those of DDs. Pre-transplant ARF increased immunoglobulin expression, which might be involved in triggering later rejection events. However, these findings must be confirmed in larger cohorts and the role of early immunoglobulin upregulation in zero-biopsies needs further clarification.
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