Research study of some RAM antennas Final report, 18 Nov. 1964 - 18 Jun. 1965

Input impedance and radiation pattern determinations for cylindrical gap, waveguide excited and circular waveguide slot antenna array

Glucose metabolism and oscillatory behavior of pancreatic islets

A variety of oscillations are observed in pancreatic islets.We establish a model, incorporating two oscillatory systems of different time scales: One is the well-known bursting model in pancreatic beta-cells and the other is the glucose-insulin feedback model which considers direct and indirect feedback of secreted insulin. These two are coupled to interact with each other in the combined model, and two basic assumptions are made on the basis of biological observations: The conductance g_{K(ATP)} for the ATP-dependent potassium current is a decreasing function of the glucose concentration whereas the insulin secretion rate is given by a function of the intracellular calcium concentration. Obtained via extensive numerical simulations are complex oscillations including clusters of bursts, slow and fast calcium oscillations, and so on. We also consider how the intracellular glucose concentration depends upon the extracellular glucose concentration, and examine the inhibitory effects of insulin.Comment: 11 pages, 16 figure

Insights into GABA receptor signalling in TM3 Leydig cells

gamma-Aminobutyric acid (GABA) is an emerging signalling molecule in endocrine organs, since it is produced by endocrine cells and acts via GABA(A) receptors in a paracrine/autocrine fashion. Testicular Leydig cells are producers and targets for GABA. These cells express GABA(A) receptor subunits and in the murine Leydig cell line TM3 pharmacological activation leads to increased proliferation. The signalling pathway of GABA in these cells is not known in this study. We therefore attempted to elucidate details of GABA(A) signalling in TM3 and adult mouse Leydig cells using several experimental approaches. TM3 cells not only express GABA(A) receptor subunits, but also bind the GABA agonist {[}H-3] muscimol with a binding affinity in the range reported for other endocrine cells (K-d = 2.740 +/- 0.721 nM). However, they exhibit a low B-max value of 28.08 fmol/mg protein. Typical GABA(A) receptor-associated events, including Cl- currents, changes in resting membrane potential, intracellular Ca2+ or cAMP, were not measurable with the methods employed in TM3 cells, or, as studied in part, in primary mouse Leydig cells. GABA or GABA(A) agonist isoguvacine treatment resulted in increased or decreased levels of several mRNAs, including transcription factors (c-fos, hsf-1, egr-1) and cell cycle-associated genes (Cdk2, cyclin D1). In an attempt to verify the cDNA array results and because egr-1 was recently implied in Leydig cell development, we further studied this factor. RT-PCR and Western blotting confirmed a time-dependent regulation of egr-1 in TM3. In the postnatal testis egr-1 was seen in cytoplasmic and nuclear locations of developing Leydig cells, which bear GABA(A) receptors and correspond well to TM3 cells. Thus, GABA acts via an untypical novel signalling pathway in TM3 cells. Further details of this pathway remain to be elucidated. Copyright (c) 2005 S. Karger AG, Base

Volatile‐mediated interactions with surface‐associated microbes: A parallelism between phyllosphere of plants and eco‐chemosphere of seaweeds

1. Both in terrestrial and aquatic realms, organisms communicate and interact with each other via volatile and non-volatile infochemicals. Terrestrial plants and seaweeds, known as prolific producers of volatiles, harbour a plethora of microbes on their surfaces like phyllosphere of plant leaves and eco-chemosphere of seaweeds, respectively, where complex ecological interactions are regulated through infochemicals. 2. Although plant leaf volatiles have been well-studied for their ecological functions in mediating microbial interactions, seaweed volatiles have been mostly investigated for their roles in climate regulation and with regard to climate change research. However, seaweed volatiles appear to be related to terrestrial plant volatiles both in terms of chemistry and ecology. 3. Synthesis. Evidence supports that seaweed volatiles can have important ecological functions in mediating interactions with microbes on their surface, just like plant leaf volatiles. Based on the existing vast literature on ecological interactions mediated by plant volatiles at phyllosphere and on the very few works on ecological roles of seaweed volatiles at eco-chemosphere, we advocate for the detailed investigation of volatile-mediated interactions regulating microbial colonisation processes on seaweed surfaces. Although of great ecological importance, this new field of research has remained largely unexplored. Thus, we also set directions for future research programs investigating the roles of seaweed volatiles at seaweed–microbe interface

Accurate Characterization of Silicon-On-Insulator MOSFETs for the Design of Low-Voltage, Low-Power RF Integrated Circuits

The maturation of low cost Silicon-on-Insulator (SOI) MOSFET technology in the microwave domain has brought about a need to develop specific characterization techniques. An original scheme is presented, which, by combining careful design of probing and calibration structures, rigorous in-situ calibration, and a new powerful direct extraction method, allows reliable identification of the parameters of the non-quasi-static small-signal model and the high-frequency noise parameters for MOSFETs. The extracted model is shown to be valid up to 40 GHz.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44055/1/10470_2004_Article_271487.pd

Microbial engineering for production of N-functionalized amino acids and amines

Mindt M, Walter T, Kugler P, Wendisch VF. Microbial engineering for production of N-functionalized amino acids and amines. Biotechnology Journal . 2020;15(7): 1900451.N‐ functionalized amines play important roles in nature and occur, for example, in the antibiotic vancomycin, the immunosuppressant cyclosporine, the cytostatic actinomycin, the siderophore aerobactin, the cyanogenic glucoside linamarin, and the polyamine spermidine. In the pharmaceutical and fine‐chemical industries N‐ functionalized amines are used as building blocks for the preparation of bioactive molecules. Processes based on fermentation and on enzyme catalysis have been developed to provide sustainable manufacturing routes to N‐ alkylated, N‐ hydroxylated, N‐ acylated, or other N‐ functionalized amines including polyamines. Metabolic engineering for provision of precursor metabolites is combined with heterologous N‐ functionalizing enzymes such as imine or ketimine reductases, opine or amino acid dehydrogenases, N‐ hydroxylases, N‐ acyltransferase, or polyamine synthetases. Recent progress and applications of fermentative processes using metabolically engineered bacteria and yeasts along with the employed enzymes are reviewed and the perspectives on developing new fermentative processes based on insight from enzyme catalysis are discussed

Rapid Insulinotropic Action of Low Doses of Bisphenol-A on Mouse and Human Islets of Langerhans: Role of Estrogen Receptor β

Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic β-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ERβ−/− mice to study whether ERβ is involved in the rapid regulation of KATP channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in β-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased KATP channel activity, increased glucose-induced [Ca2+]i signals and insulin release in β-cells from WT mice but not in cells from ERβ−/− mice. The rapid reduction in the KATP channel activity and the insulinotropic effect was seen in human cells and islets. BPA actions were stronger in human islets compared to mouse islets when the same BPA concentration was used. Our findings suggest that BPA behaves as a strong estrogen via nuclear ERβ and indicate that results obtained with BPA in mouse β-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans

Aerosolized BC-819 Inhibits Primary but Not Secondary Lung Cancer Growth

Despite numerous efforts, drug based treatments for patients suffering from lung cancer remains poor. As a promising alternative, we investigated the therapeutic potential of BC-819 for the treatment of lung cancer in mouse tumor models. BC-819 is a novel plasmid DNA which encodes for the A-fragment of Diphtheria toxin and has previously been shown to successfully inhibit tumor growth in human clinical study of bladder carcinoma. In a first set of experiments, we examined in vitro efficacy of BC-819 in human lung cancer cell-lines NCI-H460, NCI-H358 and A549, which revealed >90% reduction of cell growth. In vivo efficacy was examined in an orthotopic mouse xenograft lung cancer model and in a lung metastasis model using luminescent A549-C8-luc adenocarcinoma cells. These cells resulted in peri- and intra-bronchiolar tumors upon intrabronchial application and parenchymal tumors upon intravenous injection, respectively. Mice suffering from these lung tumors were treated with BC-819, complexed to branched polyethylenimine (PEI) and aerosolized to the mice once per week for a period of 10 weeks. Using this regimen, growth of intrabronchially induced lung tumors was significantly inhibited (p = 0.01), whereas no effect could be observed in mice suffering from lung metastasis. In summary, we suggest that aerosolized PEI/BC-819 is capable of reducing growth only in tumors arising from the luminal part of the airways and are therefore directly accessible for inhaled BC-819