Individual Effector/Regulator T Cell Ratios Impact Bone Regeneration

There is increasing evidence that T lymphocytes play a key role in controlling endogenous regeneration. Regeneration appears to be impaired in case of local accumulation of CD8+ effector T cells (TEFF), impairing endogenous regeneration by increasing a primary "useful" inflammation toward a damaging level. Thus, rescuing regeneration by regulating the heightened pro-inflammatory reaction employing regulatory CD4+ T (TReg) cells could represent an immunomodulatory option to enhance healing. Hypothesis was that CD4+ TReg might counteract undesired effects of CD8+ TEFF. Using adoptive TReg transfer, bone healing was consistently improved in mice possessing an inexperienced immune system with low amounts of CD8+ TEFF. In contrast, mice with an experienced immune system (high amounts of CD8+ TEFF) showed heterogeneous bone repair with regeneration being dependent upon the individual TEFF/TReg ratio. Thus, the healing outcome can only be improved by an adoptive TReg therapy, if an unfavorable TEFF/TReg ratio can be reshaped; if the individual CD8+ TEFF percentage, which is dependent on the individual immune experience can be changed toward a favorable ratio by the TReg transfer. Remarkably, also in patients with impaired fracture healing the TEFF/TReg ratio was higher compared to uneventful healers, validating our finding in the mouse osteotomy model. Our data demonstrate for the first time the key-role of a balanced TEFF/TReg response following injury needed to reach successful regeneration using bone as a model system. Considering this strategy, novel opportunities for immunotherapy in patients, which are at risk for impaired healing by targeting TEFF cells and supporting TReg cells to enhance healing are possible

Экспериментальное исследование синхронного генератора периодических импульсов

Приводятся результаты экспериментального исследования влияния величины нагрузки синхронного генератора периодических импульсов с обычной геометрией зубцовой зоны на форму импульсов тока. Рассматривается возможность регулировки параметров импульсов

Mesenchymal stromal cell and bone marrow concentrate therapies for musculoskeletal indications: a concise review of current literature

The interest on applying mesenchymal stromal cells (MSCs) in orthopedic disorders has risen tremendously in the last years due to scientific successes in preclinical in vitro and animal model studies. In a wide range of diseases and injuries of the musculoskeletal system, MSCs are currently under evaluation, but so far have found access to clinical use only in few cases. The current assignment is to translate the acquired knowledge into clinical practice. Therefore, this review aims at presenting a synopsis of the up-to-date status of the use of MSCs and MSC related cell products in musculoskeletal indications. Clinical studies were included, whereas preclinical and animal study data not have been considered. Most studies published so far investigate the final outcome applying bone marrow derived MSCs. In fewer trials the use of adipose tissue derived MSCs and allogenic MSCs was investigated in different applications. Although the reported results are equivocal in the current literature, the vast majority of the studies shows a benefit of MSC based therapies depending on the cell sources and the indication in clinical use. In summary, the clinical use of MSCs in patients in orthopedic indications has been found to be safe. Standardized protocols and clear definitions of the mechanisms of action and the mode and timing of application as well as further coordinated research efforts will be necessary for finally adding MSC based therapies in standard operating procedures and guidelines for the clinicians treating orthopedic disorders

Prolyl hydroxylase domain 2 protein is a strong prognostic marker in human gastric cancer

Objective: According to recent research, prolyl hydroxylase domain 2 protein (PHD2) plays an important role in human carcinogenesis by inducing neovascularization and tumor growth. The aim of this study was to evaluate PHD2 expression patterns in primary gastric adenocarcinoma and to test for a potential predictive value of PHD2 expression in gastric cancer patients. Methods: In a total of 121 patients, PHD2 expression was investigated by immunohistochemistry in paraffin- embedded tissue and correlated with clinicopathological parameters and patient survival. Results: 64 of 121 gastric carcinomas (52.9%) showed PHD2 expression in tumor cell cytoplasm. In univariate analysis, PHD2- negative patients had a significantly shortened survival in compariso

Extending Quantum Links: Modules for Fiber- and Memory-Based Quantum Repeaters

We analyze elementary building blocks for quantum repeaters based on fiber channels and memory stations. Implementations are considered for three different physical platforms, for which suitable components are available: quantum dots, trapped atoms and ions, and color centers in diamond. We evaluate and compare the performances of basic quantum repeater links for these platforms both for present-day, state-of-the-art experimental parameters as well as for parameters that could in principle be reached in the future. The ultimate goal is to experimentally explore regimes at intermediate distances, up to a few 100 km, in which the repeater-assisted secret key transmission rates exceed the maximal rate achievable via direct transmission. We consider two different protocols, one of which is better adapted to the higher source clock rate and lower memory coherence time of the quantum dot platform, while the other circumvents the need of writing photonic quantum states into the memories in a heralded, non-destructive fashion. The elementary building blocks and protocols can be connected in a modular form to construct a quantum repeater system that is potentially scalable to large distances.Comment: 48 pages in Word style, "White Paper" of Q.Link.X Consortiu

Exploring the photon-number distribution of bimodal microlasers with a transition edge sensor

The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework ERC Grant Agreement No. 615613, within the EURAMET joint research project MIQC2 from the European Union's Horizon 2020 Research and Innovation Programme and the EMPIR Participating States and from the German Research Foundation within the project RE2974/10-1. The authors thank the State of Bavaria for financial support.A photon-number resolving transition edge sensor (TES) is used to measure the photon-number distribution of two microcavity lasers. The investigated devices are bimodal microlasers with similar emission intensity and photon statistics with respect to the photon auto-correlation. Both high-β microlasers show partly thermal and partly coherent emission around the lasing threshold. For higher pump powers, the strong mode of microlaser { A } emits Poissonian distributed photons while the emission of the weak mode is thermal. In contrast, laser { B } shows a bistability resulting in overlayed thermal and Poissonian distributions. While a standard Hanbury Brown and Twiss experiment cannot distinguish between simple thermal emission of laser { A } and the temporal mode switching of the bistable laser { B }, TESs allow us to measure the photon-number distribution which provides important insight into the underlying emission processes. Indeed, our experimental data and its theoretical description by a master equation approach show that TESs are capable of revealing subtle effects like mode switching of bimodal microlasers. As such our studies clearly demonstrate the benefit and importance of investigating nanophotonic devices via photon-number resolving transition edge sensors.PostprintPeer reviewe

Soziale Strukturen und wirtschaftliche Konjunkturen im frühneuzeitlichen Bamberg

Die fünf Beiträge des vorliegenden Bandes untersuchen die Sozialstruktur und Wirtschaftsentwicklung der fürstbischöflichen Residenzstadt Bamberg. Drei Analysen von Steuerlisten und Steuerbeschreibungen des 16. und 17. Jahrhunderts geben Aufschluss über die Vermögensverhältnisse im Bereich des Stadtgerichts und der Immunitäten, die soziale Schichtung der Bamberger Bevölkerung und die soziale Topographie der Stadt. Diese Studien werden ergänzt durch zwei Untersuchungen zum Bamberger Waisenhaus. Sie stellen die baulichen, administrativen und personellen Strukturen dieser Institution vor, beschreiben den Alltag der Waisenkinder und zeichnen auf der Basis der Waisenhausrechnungen ökonomische Zyklen und Krisen des 17. und 18. Jahrhunderts nach

Geo-Biological Investigations on Azooxanthellate Cold-Water Coral Reefs on the Carbonate Mounds Along the Celtic Continental Slope

Northeast Atlantic 2004 Cruise No. 61, Leg 1 April 19 to May 4, 2004, Lisbon – Cor

Local immune cell contributions to fracture healing in aged individuals – A novel role for interleukin 22

Aging: immune protein's role in delayed bone fracture healing Neutralizing a key cytokine, a signaling protein affecting the immune system could rejuvenate the healing process following prolonged inflammatory responses to bone fractures in elderly patients. Healing patterns vary widely in the elderly following injuries such as bone fractures, and scientists now believe that a patient's individual innate and adaptive immune profile directly affects the healing process. A short-lived pro-inflammatory response is needed to kickstart healthy healing, but a longer-lasting response can be damaging. In experiments on aged mouse models, the team led by Katharina Schmidt-Bleek at the Julius Wolff Institute in Berlin, Germany, demonstrated that high levels of the cytokine interleukin-22 impaired bone regeneration. Elevated interleukin-22 levels resulted from chronically elevated inflammation and inflammaging, prevalent in elderly patients. The team treated the mice to neutralize interleukin-22, which accelerated the healing process. With increasing age, the risk of bone fractures increases while regenerative capacity decreases. This variation in healing potential appears to be linked to adaptive immunity, but the underlying mechanism is still unknown. This study sheds light on immunoaging/inflammaging, which impacts regenerative processes in aging individuals. In an aged preclinical model system, different levels of immunoaging were analyzed to identify key factors that connect immunoaged/inflammaged conditions with bone formation after long bone fracture. Immunological facets, progenitor cells, the microbiome, and confounders were monitored locally at the injury site and systemically in relation to healing outcomes in 12-month-old mice with distinct individual levels of immunoaging. Bone tissue formation during healing was delayed in the immunoaged group and could be associated with significant changes in cytokine levels. A prolonged and amplified pro-inflammatory reaction was caused by upregulated immune cell activation markers, increased chemokine receptor availability and a lack of inhibitory signaling. In immunoaged mice, interleukin-22 was identified as a core cell signaling protein that played a central role in delayed healing. Therapeutic neutralization of IL-22 reversed this specific immunoaging-related disturbed healing. Immunoaging was found to be an influencing factor of decreased regenerative capacity in aged individuals. Furthermore, a novel therapeutic strategy of neutralizing IL-22 may successfully rejuvenate healing in individuals with advanced immune experiences