Resolution and enhancement in nanoantenna-based fluorescence microscopy

Single gold nanoparticles can act as nanoantennas for enhancing the fluorescence of emitters in their near-fields. Here we present experimental and theoretical studies of scanning antenna-based fluorescence microscopy as a function of the diameter of the gold nanoparticle. We examine the interplay between fluorescence enhancement and spatial resolution and discuss the requirements for deciphering single molecules in a dense sample. Resolutions better than 20 nm and fluorescence enhancement up to 30 times are demonstrated experimentally. By accounting for the tip shaft and the sample interface in finite-difference time-domain calculations, we explain why the measured fluorescence enhancements are higher in the presence of an interface than the values predicted for a homogeneous environment.Comment: 10 pages, 3 figures. accepted for publication in Nano Letter

Recent results of basic and clinical research in MEN1:opportunities to improve early detection and treatment

Due to the variable expression of multiple endocrine neoplasia type 1 (MEN1), it is difficult to predict the course of the disease. However, knowledge about the normal function of the MEN1 gene product, together with the effects of cellular derangement by subsequent genetic events, has increased considerably. At first, the possible existence of a genotype-phenotype correlation is discussed. Thus, mild-and late-onset phenotypes may be distinguished from more malignant phenotypes depending on the character of the primary MEN1 disease gene mutation. Subsequently, tumor-promoting factors such as gender, additional genetic mutations and ecogenetic factors may contribute to the course of the disease. New developments in management are based on the knowledge and experience of the multidisciplinary teams involved. Finally, the metabolic effects of MEN1 mutations in aged patients are discussed. Early identification of predisposition to the disease, together with knowledge about the natural history of specific mutations, risks of additional mutations and periodic clinical monitoring, allow early treatment and may improve life expectancy and quality of life

Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus

Human islet amyloid polypeptide (hIAPP), a pancreatic islet protein of 37 amino acids, is the main component of islet amyloid, seen at autopsy in patients with type 2 diabetes mellitus (DM2). To investigate the roles of hIAPP and islet amyloid in DM2, we generated transgenic mice expressing hIAPP in their islet beta cells. In this study, we found that after a long-term, high-fat diet challenge islet amyloid was observed in only 4 of 19 hIAPP transgenic mice. hIAPP transgenic females exhibited severe glucose intolerance, which was associated with a downregulation of GLUT-2 mRNA expression. In isolated islets from hIAPP males cultured for 3 weeks on high-glucose medium, the percentage of amyloid containing islets increased from 5.5% to 70%. This ex vivo system will allow a more rapid, convenient, and specific study of factors influencing islet amyloidosis as well as of therapeutic strategies to interfere with this pathological process

Low doses of the novel caspase-inhibitor GS-9450 leads to lower caspase-3 and -8 expression on peripheral CD4+ and CD8+ T-cells

Chronic hepatitis C virus (HCV) infection is characterized by increased rates of apoptotic hepatocytes and activated caspases have been shown in HCV-infected patients. GS-9450, a novel caspase-inhibitor has demonstrated hepatoprotective activity in fibrosis/apoptosis animal models. This study evaluated the effects of GS-9450 on peripheral T-cell apoptosis in chronic HCV-infected patients. As sub study of the GS-US-227-0102, a double-blind, placebo-controlled phase 2a trial evaluating the safety and tolerability of GS-9450, apoptosis of peripheral CD4+ and CD8+ T-cells was measured using activated caspase-3, activated caspase-8 and CD95 (Fas). Blood samples were drawn at baseline, day 14 after therapy and at 5 weeks off-treatment follow-up in the first cohort of 10 mg. In contrast to the placebo-treated patients, GS-9450 caused a median of 46% decrease in ALT-values from baseline to day 14 in all treated patients (median of 118–64 U/l) rising again to a median of 140 U/l (19%) at 5 weeks off-treatment follow-up. In GS9450-treated patients, during treatment and follow-up, percentages of activated caspase-3+ and caspase-8 expression tended to decrease, in contrast to placebo-treated patients. Interestingly, compared to healthy controls, higher percentages of caspase-3 and caspase-8 positive CD4+ and CD8+ T-cells were demonstrated in HCV-infected patients at baseline. Decreased ALT-values were observed in all HCV-infected patients during treatment with low dose of the caspase-inhibitor GS-9450 accompanied by a lower expression of caspase-3 and -8 on peripheral T-cells. Furthermore, at baseline percentages of activated caspase-3, activated caspase-8 and CD95+ T-cells were higher in chronic HCV-infected patients compared to healthy controls

B Cells as Prognostic Biomarker After Surgery for Colorectal Liver Metastases

Background: The aim of this study was to identify more accurate variables to improve prognostication of individual patients with colorectal liver metastases (CRLM). Clinicopathological characteristics only partly explain the large range in survival rates. Methods: MessengerRNA expression profiles of resected CRLM of two patient groups were analysed by mRNA sequencing: poor survivors (death from recurrent disease 60 months after surgery). Tumour and adjacent liver parenchyma samples were analysed. Results: MessengerRNA expression profiling of the tumour samples identified 77 genes that were differentially expressed between the two survival groups at a False Discovery Rate (FDR) <0.1. In the adjacent liver parenchyma samples only one gene, MTRNR2L1, showed significantly higher expression in the good survivors. Pathway analysis showed higher expression of immune-related and stroma-related genes in tumour samples from good survivors. Expression data was then validated by immunohistochemistry in two cohorts comprising a total of 125 patients. Immunohistochemical markers that showed to be associated with good survival in the total cohort were: high K/L+ infiltration in tumour stroma [p = 0.029; OR 2.500 (95% CI 1.100–5.682)] and high CD79A+ infiltration in tumour stroma [p = 0.036; OR 2.428 (95%CI 1.062–5.552)]. Conclusions: A high stromal infiltration of CD79A+ B cells and K/L+ plasma cells might be favourable prognostic biomarkers after surgery for CRLM

Nanoantennas for visible and infrared radiation

Nanoantennas for visible and infrared radiation can strongly enhance the interaction of light with nanoscale matter by their ability to efficiently link propagating and spatially localized optical fields. This ability unlocks an enormous potential for applications ranging from nanoscale optical microscopy and spectroscopy over solar energy conversion, integrated optical nanocircuitry, opto-electronics and density-ofstates engineering to ultra-sensing as well as enhancement of optical nonlinearities. Here we review the current understanding of optical antennas based on the background of both well-developed radiowave antenna engineering and the emerging field of plasmonics. In particular, we address the plasmonic behavior that emerges due to the very high optical frequencies involved and the limitations in the choice of antenna materials and geometrical parameters imposed by nanofabrication. Finally, we give a brief account of the current status of the field and the major established and emerging lines of investigation in this vivid area of research.Comment: Review article with 76 pages, 21 figure

The Effect of Histopathological Growth Patterns of Colorectal Liver Metastases on the Survival Benefit of Adjuvant Hepatic Arterial Infusion Pump Chemotherapy

Background: Histopathological growth patterns (HGPs) are a prognostic biomarker in colorectal liver metastases (CRLM). Desmoplastic HGP (dHGP) is associated with liver-only recurrence and superior overall survival (OS), while non-dHGP is associated with multi-organ recurrence and inferior OS. This study investigated the predictive value of HGPs for adjuvant hepatic arterial infusion pump (HAIP) chemotherapy in CRLM. Methods: Patients undergoing resection of CRLM and perioperative systemic chemotherapy in two centers were included. Survival outcomes and the predictive value of HAIP versus no HAIP per HGP group were evaluated through Kaplan–Meier and Cox regression methods, respectively. Results:We included 1233 patients. In the dHGP group (n = 291, 24%), HAIP chemotherapy was administered in 75 patients (26%). In the non-dHGP group (n = 942, 76%), HAIP chemotherapy was administered in 247 patients (26%). dHGP was associated with improved overall survival (OS, HR 0.49, 95% CI 0.32–0.73, p &lt; 0.001). HAIP chemotherapy was associated with improved OS (HR 0.61, 95% CI 0.45–0.82, p &lt; 0.001). No interaction could be demonstrated between HGP and HAIP on OS (HR 1.29, 95% CI 0.72–2.32, p = 0.40).Conclusions: There is no evidence that HGPs of CRLM modify the survival benefit of adjuvant HAIP chemotherapy in patients with resected CRLM.</p