University of Applied Sciences Mainz

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

BACKGROUND: Influential studies have cast doubt on the validity of retrospective reports by adults of their own adverse experiences in childhood. Accordingly, many researchers view retrospective reports with scepticism. METHOD: A computer-based search, supplemented by hand searches, was used to identify studies reported between 1980 and 2001 in which there was a quantified assessment of the validity of retrospective recall of sexual abuse, physical abuse, physical/emotional neglect or family discord, using samples of at least 40. Validity was assessed by means of comparisons with contemporaneous, prospectively obtained, court or clinic or research records; by agreement between retrospective reports of two siblings; and by the examination of possible bias with respect to differences between retrospective and prospective reports in their correlates and consequences. Medium- to long-term reliability of retrospective recall was determined from studies in which the test-retest period extended over at least 6 months. RESULTS: Retrospective reports in adulthood of major adverse experiences in childhood, even when these are of a kind that allow reasonable operationalisation, involve a substantial rate of false negatives, and substantial measurement error. On the other hand, although less easily quantified, false positive reports are probably rare. Several studies have shown some bias in retrospective reports. However, such bias is not sufficiently great to invalidate retrospective case-control studies of major adversities of an easily defined kind. Nevertheless, the findings suggest that little weight can be placed on the retrospective reports of details of early experiences or on reports of experiences that rely heavily onjudgement or interpretation. CONCLUSION: Retrospective studies have a worthwhile place in research, but further research is needed to examine possible biases in reporting.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Eighth Edition of the JCA Special Issue continues to maintain this methodology and rigor in order to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Eighth Edition, like its predecessor, continues to apply the category and grading system definitions in fact sheets. The general layout and concept of a fact sheet that was introduced in the Fourth Edition, has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease entity or medical condition. The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

Nanographenes, or extended polycyclic aromatic hydrocarbons, have been attracting renewed and more widespread attention since the first experimental demonstration of graphene in 2004. However, the atomically precise fabrication of nanographenes has thus far been achieved only through synthetic organic chemistry. The precise synthesis of quasi-zero-dimensional nanographenes, i.e. graphene molecules, has witnessed rapid developments over the past few years, and these developments can be summarized in four categories: (1) non-conventional methods, (2) structures incorporating seven- or eight-membered rings, (3) selective heteroatom doping, and (4) direct edge functionalization. On the other hand, one-dimensional extension of the graphene molecules leads to the formation of graphene nanoribbons (GNRs) with high aspect ratios. The synthesis of structurally well-defined GNRs has been achieved by extending nanographene synthesis to longitudinally extended polymeric systems. Access to GNRs thus becomes possible through the solution-mediated or surface-assisted cyclodehydrogenation, or "graphitization," of tailor-made polyphenylene precursors. In this review, we describe recent progress in the "bottom-up" chemical syntheses of structurally well-defined nanographenes, namely graphene molecules and GNRs.

The direct synthetic organic use of electricity is currently experiencing a renaissance. More synthetically oriented laboratories working in this area are exploiting both novel and more traditional concepts, paving the way to broader applications of this niche technology. As only electrons serve as reagents, the generation of reagent waste is efficiently avoided. Moreover, stoichiometric reagents can be regenerated and allow a transformation to be conducted in an electrocatalytic fashion. However, the application of electroorganic transformations is more than minimizing the waste footprint, it rather gives rise to inherently safe processes, reduces the number of steps of many syntheses, allows for milder reaction conditions, provides alternative means to access desired structural entities, and creates intellectual property (IP) space. When the electricity originates from renewable resources, this surplus might be directly employed as a terminal oxidizing or reducing agent, providing an ultra-sustainable and therefore highly attractive technique. This Review surveys recent developments in electrochemical synthesis that will influence the future of this area.

Abstract An anionic and a cationic bipolar amphiphile containing rigid biphenyl cores were synthesized. The compounds were dissolved in a mixture of dimethylsulfoxide (DMSO) and water and pure water, respectively. When a solid substrate with a positively charged planar surface is immersed in the solution containing the negatively charged bipolar amphiphile, a monolayer of the amphiphile is adsorbed and due to its bipolar structure the surface charge is reversed. After rinsing in pure water the substrate is immersed in the solution containing the positively charged bipolar amphiphile. Again a monolayer is adsorbed but now the original surface charge is restored. By repeating both steps in a cyclic fashion alternating multilayer assemblies of both compounds are obtained. It is demonstrated that multilayer films, composed of at least 35 consecutively alternating layers, which corresponds to a total film thickness of 170 nm can be assembled.

In the present multi-center study, non-submerged ITI implants were prospectively followed to evaluate their long-term prognosis in fully and partially edentulous patients. In a total of 1003 patients, 2359 implants were consecutively inserted. Following a healing period of 3-6 months, the successfully integrated implants were restored with 393 removable and 758 fixed restorations. Subsequently, all consecutive implants were documented annually up to 8 years. At each examination, the clinical status of all implants was evaluated according to predefined criteria of success. Therefore, the data base allowed the evaluation of 8-year cumulative survival and success rates for 2359 implants. In addition, cumulative success rates were calculated for implant subgroups divided per implant type, implant length, and implant location. Furthermore, the actual 5-year survival and success rates could be determined for 488 implants. During the healing period, 13 implants did not successfully integrate, whereas 2346 implants fulfilled the predefined criteria of success. This corresponds with an early failure rate of 0.55%. During follow-up, 19 implants were classified as failures due to several reasons. In addition, 17 implants (approximately 0.8%) demonstrated at the last annual examination a suppurative periimplant infection. Including 127 drop out implants (= 5.4% drop out rate) into the calculation, the 8-year cumulative survival and success rates resulted in 96.7% and 93.3%, respectively. The analysis of implant subgroups showed slightly more favorable cumulative success rates for screw type implants (> 95%) compared to hollow-cylinder implants (91.3%), and clearly better success rates for mandibular implants (approximately 95%) when compared to maxillary implants (approximately 87%). The actual 5-year survival and success rates of 488 implants with 98.2% and 97.3%, respectively, were slightly better than the estimated 5-year cumulative survival and success rates of 2359 implants indicating that the applied life table analysis is a reliable statistical method to evaluate the long-term prognosis of dental implants. It can be concluded that non-submerged ITI implants maintain success rates well above 90% in different clinical centers for observation periods up to 8 years.

Dendritic cells (DC) form a specialized system for presenting Ag to naive or quiescent T cells and consequently play a central role in the induction of T and B cell immunity. In this study we used DC generated from peripheral progenitors to analyze the effect of IL-10 on the accessory function of human DC. We demonstrate that immature DC, harvested on days 9 to 11 and exposed to IL-10 for the last 2 days of culture, show a strongly reduced capacity to stimulate a CD4+ T cell response in an allogeneic MLR in a dose-dependent manner. In contrast, fully mature DC are completely resistant to the effects of IL-10. These results were obtained in both an alloantigen-induced MLR and an anti-CD3 mAb-induced response of primed and naive (CD45RA+) CD4+ T cells. FACS analysis revealed inhibition of the up-regulation of the costimulatory molecules CD58 and CD86 and the specific DC marker CD83 in DC pretreated with IL-10. These data suggest that IL-10 inhibited the development of fully mature DC. Furthermore, DC precultured with IL-10, but not controls, induced a state of alloantigen-specific anergy in CD4+ T cells and of peptide-specific anergy in the influenza hemagglutinin-specific T cell clone HA1.7. Analysis of the supernatants of these anergic T cells revealed a reduced production of IL-2 and IFN-gamma compared with that in control cells. Collectively, these data suggest that IL-10 converts immature DC into tolerogenic APC, which might be a useful tool in the therapy of patients with autoimmune or allergic diseases.

Influx of macrophages plays a crucial role in tissue repair. However, the precise function of macrophages during the healing response has remained a subject of debate due to their functional dichotomy as effectors of both tissue injury and repair. We tested the hypothesis that macrophages recruited during the diverse phases of skin repair after mechanical injury exert specific functions to restore tissue integrity. For this purpose, we developed a mouse model that allows conditional depletion of macrophages during the sequential stages of the repair response. Depletion of macrophages restricted to the early stage of the repair response (inflammatory phase) significantly reduced the formation of vascularized granulation tissue, impaired epithelialization, and resulted in minimized scar formation. In contrast, depletion of macrophages restricted to the consecutive mid-stage of the repair response (phase of tissue formation) resulted in severe hemorrhage in the wound tissue. Under these conditions, transition into the subsequent phase of tissue maturation and wound closure did not occur. Finally, macrophage depletion restricted to the late stage of repair (phase of tissue maturation) did not significantly impact the outcome of the repair response. These results demonstrate that macrophages exert distinct functions during the diverse phases of skin repair, which are crucial to control the natural sequence of repair events.

The use of electricity instead of stoichiometric amounts of oxidizers or reducing agents in synthesis is very appealing for economic and ecological reasons, and represents a major driving force for research efforts in this area. To use electron transfer at the electrode for a successful transformation in organic synthesis, the intermediate radical (cation/anion) has to be stabilized. Its combination with other approaches in organic chemistry or concepts of contemporary synthesis allows the establishment of powerful synthetic methods. The aim in the 21st Century will be to use as little fossil carbon as possible and, for this reason, the use of renewable sources is becoming increasingly important. The direct conversion of renewables, which have previously mainly been incinerated, is of increasing interest. This Review surveys many of the recent seminal important developments which will determine the future of this dynamic emerging field.

Abstract Improved activity–composition relationships for biotite, garnet and silicate liquid are used to construct updated P – T grids and pseudosections for high‐grade metapelites. The biotite model involves Ti charge‐balanced by hydrogen deprotonation on the hydroxyl site, following the substitution , where HD represents the hydroxyl site. Relative to equivalent biotite‐breakdown melting reactions in P – T grids in K 2 O–FeO–MgO–Al 2 O 3 –SiO 2 –H 2 O (KFMASH), those in K 2 O–FeO–MgO–Al 2 O 3 –SiO 2 –H 2 O–TiO 2 –O 2 (KFMASHTO) occur at temperatures close to 50 °C higher. A further consequence of the updated activity models is that spinel‐bearing equilibria occur to higher temperature and higher pressure. In contrast, the addition of Na 2 O and CaO to KFMASH to make the Na 2 O–CaO–K 2 O–FeO–MgO–Al 2 O 3 –SiO 2 –H 2 O (NCKFMASH) system lowers key biotite‐breakdown melting reactions in P – T space relative to KFMASH. Combination of the KFMASHTO and NCKFMASH systems to make Na 2 O–CaO–K 2 O–FeO–MgO–Al 2 O 3 –SiO 2 –H 2 O–TiO 2 –O 2 (NCKFMASHTO) results in key biotite‐breakdown melting reactions occurring at temperatures intermediate between those in KFMASHTO and those in NCKFMASH. Given such differences, the choice of model system will be critical to inferred P – T conditions in the application of mineral equilibria modelling to rocks. Further, pseudosections constructed in KFMASH, NCKFMASH and NCKFMASHTO for several representative rock compositions show substantial differences not only in the P – T conditions of key metamorphic assemblages but also overall topology, with the calculations in NCKFMASHTO more reliably reflecting equilibria in rocks. Application of mineral equilibria modelling to rocks should be undertaken in the most comprehensive system possible, if reliable quantitative P – T information is to be derived.

Cells are integral to all forms of life due to their compartmentalization by the plasma membrane. However, living organisms are immensely complex. Thus there is a need for simplified and controllable models of life for a deeper understanding of fundamental biological processes and man-made applications. This is where the bottom-up approach of synthetic biology comes from: a stepwise assembly of biomimetic functionalities ultimately into a protocell. A fundamental feature of such an endeavor is the generation and control of model membranes such as liposomes and polymersomes. We compare and contrast liposomes and polymersomes for a better a priori choice and design of vesicles and try to understand the advantages and shortcomings associated with using one or the other in many different aspects (properties, synthesis, self-assembly, applications) and which aspects have been studied and developed with each type and update the current development in the field.

Critics of foreign aid programs argue that these funds often support corrupt governments and inefficient bureaucracies. Supporters argue that foreign aid can be used to reward good governments. This paper documents that there is no evidence that less corrupt governments receive more foreign aid. On the contrary, according to some measures of corruption, more corrupt governments receive more aid. Also, we could not find any evidence that an increase in foreign aid reduces corruption.

Experiments and basic Physics of exciton diffusion in organic semiconductors are reviewed.

The review summarizes current trends and developments in the polymerization of alkylene oxides in the last two decades since 1995, with a particular focus on the most important epoxide monomers ethylene oxide (EO), propylene oxide (PO), and butylene oxide (BO). Classical synthetic pathways, i.e., anionic polymerization, coordination polymerization, and cationic polymerization of epoxides (oxiranes), are briefly reviewed. The main focus of the review lies on more recent and in some cases metal-free methods for epoxide polymerization, i.e., the activated monomer strategy, the use of organocatalysts, such as N-heterocyclic carbenes (NHCs) and N-heterocyclic olefins (NHOs) as well as phosphazene bases. In addition, the commercially relevant double-metal cyanide (DMC) catalyst systems are discussed. Besides the synthetic progress, new types of multifunctional linear PEG (mf-PEG) and PPO structures accessible by copolymerization of EO or PO with functional epoxide comonomers are presented as well as complex branched, hyperbranched, and dendrimer like polyethers. Amphiphilic block copolymers based on PEO and PPO (Poloxamers and Pluronics) and advances in the area of PEGylation as the most important bioconjugation strategy are also summarized. With the ever growing toolbox for epoxide polymerization, a "polyether universe" may be envisaged that in its structural diversity parallels the immense variety of structural options available for polymers based on vinyl monomers with a purely carbon-based backbone.

Arylated products are found in various fields of chemistry and represent essential entities for many applications. Therefore, the formation of this structural feature represents a central issue of contemporary organic synthesis. By the action of electricity the necessity of leaving groups, metal catalysts, stoichiometric oxidizers, or reducing agents can be omitted in part or even completely. The replacement of conventional reagents by sustainable electricity not only will be environmentally benign but also allows significant short cuts in electrochemical synthesis. In addition, this methodology can be considered as inherently safe. The current survey is organized in cathodic and anodic conversions as well as by the number of leaving groups being involved. In some electroconversions the reagents used are regenerated at the electrode, whereas in other electrotransformations free radical sequences are exploited to afford a highly sustainable process. The electrochemical formation of the aryl-substrate bond is discussed for aromatic substrates, heterocycles, other multiple bond systems, and even at saturated carbon substrates. This survey covers most of the seminal work and the advances of the past two decades in this area.

The severe limitations of fossil fuels and finite resources influence the scientific community to reconsider chemical synthesis and establish sustainable techniques. Several promising methods have emerged, and electro-organic conversion has attracted particular attention from international academia and industry as an environmentally benign and cost-effective technique. The easy application, precise control, and safe conversion of substrates with intermediates only accessible by this method reveal novel pathways in synthetic organic chemistry. The popularity of electricity as a reagent is accompanied by the feasible conversion of bio-based feedstocks to limit the carbon footprint. Several milestones have been achieved in electro-organic conversion at rapid frequency, which have opened up various perspectives for forthcoming processes.

The development of graphene based metal and metal oxide nano composites is reviewed with special focus on their synthesis and their applications in electronics, batteries, solar cells and analytics.

The relationship between crystallisation and melting behaviour of copolymers and their morphology has been the subject of intensive discussion. One of the main points of interest is the distribution of the noncrystallizable units within the partially crystalline systems. For the explanation of physical properties of copolymers very often equilibrium theories (1, 2) are applied which start from the basic assumption that the noncrystallizable units of the polymer chains are rejected from the crystalline regions. On the other hand, the results of some structure studies by means of small angle X-ray scattering revealed strong evidence, that for example in branched polyethylene the comonomer units are partially incorporated in the crystal (3, 4).

Besides the wide use of engineered nanomaterials (NMs) in technical products, their applications are not only increasing in biotechnology and biomedicine, but also in the environmental field. While the physico-chemical properties and behaviour of NMs can be characterized accurately under idealized conditions, this is no longer the case in complex physiological or natural environments. Herein, proteins and other biomolecules rapidly bind to NMs, forming a protein/biomolecule corona that critically affects the NMs' (patho)biological and technical identities. As the corona impacts the in vitro and/or in vivo NM applications in humans and ecosystems, a mechanistic understanding of its relevance and of the biophysical forces regulating corona formation is mandatory. Based on recent insights, we here critically review and present an updated concept of corona formation and evolution. We comment on how corona signatures may be linked to effects at the nano-bio interface in physiological and environmental systems. In order to comprehensively analyse corona profiles and to mechanistically understand the coronas' biological/ecological impact, we present a tiered multidisciplinary approach. To stimulate progress in this field, we introduce the potential impact of the corona for NM-microbiome-(human)host interactions and the novel concept of 'nanologicals', i.e., the nanomaterial-specific targeting of molecular machines. We conclude by discussing the relevant challenges that still need to be resolved in this field.