Combined XPS and DFT investigation of the adsorption modes of methyl enol ether functionalized cyclooctyne on Si(001)

The reaction of methyl enol ether functionalized cyclooctyne on the silicon (001) surface was investigated by means of X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT). Three different groups of final states were identified; all of them bind on Si(001) via the strained triple bond of cyclooctyne but they differ in the configuration of the methyl enol ether group. The majority of molecules adsorbs without additional reaction of the enol ether group; the relative contribution of this configuration to the total coverage depends on substrate temperature and coverage. Further configurations include enol ether groups which reacted on the silicon surface either via ether cleavage or enol ether groups which transformed on the surface into a carbonyl group

Tuberculous coxitis with trochanteric bursitis manifesting a year after immigration to Germany: a case report

Abstract Background Osteoarticular tuberculosis is rare in Germany. In particular, trochanteric bursitis is an extremely rare manifestation of osteoarticular tuberculosis. We describe a case of tuberculous coxitis with trochanteric bursitis, successfully treated with a fourfold tuberculostatic therapy. Case presentation We report the case of a 43-year-old human immunodeficiency virus-negative Sudanese man with osteoarticular tuberculosis, who was originally admitted with the suspected diagnosis of ankylosing spondylitis. Low grade fever together with the positive result of an interferon-gamma release assay test as well as findings from magnetic resonance imaging provided clues to the diagnosis. A definitive diagnosis could be set after a computed tomography-guided biopsy. Conclusions Apart from a rare involvement pattern of osteoarticular tuberculosis, including trochanteric bursitis, this case highlights the increasing importance of osteoarticular tuberculosis as a differential diagnosis of rheumatic disorders. With the growing migration flows from tuberculosis-endemic African countries, clinicians in central and northern Europe may be more frequently confronted with atypical involvement patterns of osteoarticular tuberculosis

Click Chemistry in Ultra‐high Vacuum – Tetrazine Coupling with Methyl Enol Ether Covalently Linked to Si(001)

The additive‐free tetrazine/enol ether click reaction was performed in ultra‐high vacuum (UHV) with an enol ether group covalently linked to a silicon surface: Dimethyl 1,2,4,5‐tetrazine‐3,6‐dicarboxylate molecules were coupled to the enol ether group of a functionalized cyclooctyne which was adsorbed on the silicon (001) surface via the strained triple bond of cyclooctyne. The reaction was observed at a substrate temperature of 380 K by means of X‐ray photoelectron spectroscopy (XPS). A moderate energy barrier was deduced for this click reaction in vacuum by means of density functional theory based calculations, in good agreement with the experimental results. This UHV‐compatible click reaction thus opens a new, flexible route for synthesizing covalently bound organic architectures

Repair of a segmental long bone defect in human by implantation of a novel multiple disc graft

Large segmental defects of the weight bearing long bones are very difficult to reconstruct. Current treatment options are afflicted with several limitations and disadvantages. We describe a novel approach to regenerate a segmental long bone defect in a patient using a multiple disc graft. Decellularized bovine trabecular bone discs were seeded with autologous bone marrow cells and cultured in a perfusion chamber for three weeks. Multiple cell-seeded discs were implanted to close a 72 mm defect of the distal tibia in a 58-year-old woman, and fixed by an intramedullary nail. Bone formation was assessed non-invasively by plain radiographs and 18F-labeled sodium fluoride-based co-registration of positron emission- and computed tomography (PET/CT). Bone was actively formed around the grafted defect as early as six weeks after surgery. Because the tibia was sufficiently stabilized, the patient was able to freely walk with full weight bearing 6 weeks after surgery. The uneventful two-year follow-up and the satisfaction of the patient demonstrated the success of the procedure. Therefore the use of multiple cell-seeded disc grafts can be considered as a treatment alternative for patients with segmental long bone defects

Dendritic cell-mediated immune humanization of mice: implications for allogeneic and xenogeneic stem cell transplantation

De novo regeneration of immunity is a major problem after allogeneic hematopoietic stem cell transplantation (HCT). HCT modeling in severely compromised immune-deficient animals transplanted with human stem cells is currently limited because of incomplete maturation of lymphocytes and scarce adaptive responses. Dendritic cells (DC) are pivotal for the organization of lymph nodes and activation of naive T and B cells. Human DC function after HCT could be augmented with adoptively transferred donor-derived DC. In this study, we demonstrate that adoptive transfer of long-lived human DC coexpressing high levels of human IFN-α, human GM-CSF, and a clinically relevant Ag (CMV pp65 protein) promoted human lymphatic remodeling in immune-deficient NOD.Rag1(-/-).IL-2rγ(-/-) mice transplanted with human CD34(+) cells. After immunization, draining lymph nodes became replenished with terminally differentiated human follicular Th cells, plasma B cells, and memory helper and cytotoxic T cells. Human Igs against pp65 were detectable in plasma, demonstrating IgG class-switch recombination. Human T cells recovered from mice showed functional reactivity against pp65. Adoptive immunotherapy with engineered DC provides a novel strategy for de novo immune reconstitution after human HCT and a practical and effective tool for studying human lymphatic regeneration in vivo in immune deficient xenograft hosts

Dendritic Cell–Mediated Immune Humanization of Mice: Implications for Allogeneic and Xenogeneic Stem Cell Transplantation

De novo regeneration of immunity is a major problem after allogeneic hematopoietic stem cell transplantation (HCT). HCT modeling in severely compromised immune-deficient animals transplanted with human stem cells is currently limited because of incomplete maturation of lymphocytes and scarce adaptive responses. Dendritic cells (DC) are pivotal for the organization of lymph nodes and activation of naive T and B cells. Human DC function after HCT could be augmented with adoptively transferred donor-derived DC. In this study, we demonstrate that adoptive transfer of long-lived human DC coexpressing high levels of human IFN-α, human GM-CSF, and a clinically relevant Ag (CMV pp65 protein) promoted human lymphatic remodeling in immune-deficient NOD.Rag1(-/-).IL-2rγ(-/-) mice transplanted with human CD34(+) cells. After immunization, draining lymph nodes became replenished with terminally differentiated human follicular Th cells, plasma B cells, and memory helper and cytotoxic T cells. Human Igs against pp65 were detectable in plasma, demonstrating IgG class-switch recombination. Human T cells recovered from mice showed functional reactivity against pp65. Adoptive immunotherapy with engineered DC provides a novel strategy for de novo immune reconstitution after human HCT and a practical and effective tool for studying human lymphatic regeneration in vivo in immune deficient xenograft hosts

Lobular neoplasia and invasive lobular breast cancer: Inter-observer agreement for histological grading and subclassification

Lobular neoplasia (LN), invasive lobular breast cancer (ILBC) and related pleomorphic variants represent a distinct group of neoplastic mammary gland lesions. This study assessed the inter-observer agreement of histological grading in a series of ILBC and LN. 54 cases (36x ILBC, 18x LN) were evaluated by 17 observers. 3978 classification calls on various histological features, including nuclear grade, proliferative activity (Ki67 immunohistochemistry, categorical scoring), histological grade and pleomorphism were obtained. Pairwise Cohen’s kappa values were calculated and compared between various features and different observer subsets with variable histomorphological experience. In ILBC, pairwise inter-observer agreement for histological grade ranged from poor to almost perfect concordance and was higher in advanced and experienced histopathologists compared with beginners (P < 0.001). Agreement for proliferation (Ki67) ranged from slight to almost perfect concordance and was also higher in advanced and experienced histopathologists (P < 0.001). Considering different features, agreement for proliferation (Ki67) was superior to agreement for histological grade and nuclear grade, even among advanced and experienced histopathologists (P < 0.001). In LN, agreement for B-classification ranged from poor to almost perfect concordance and was higher in advanced and experienced histopathologists (P < 0.001). Considering different features, agreement for proliferation (Ki67 in LN) was superior to subclassification agreement based on conventional features, such as acinar distention and nuclear grade (P < 0.001). In summary, pairwise inter-observer concordance of histological grading of ILBC and LN is dependent on histomorphological experience. Assessment of proliferation by Ki67 immunohistochemistry is associated with favorable inter-observer agreement and can improve histological grading of ILBC as well as LN