Insulin receptor substrate (IRS) proteins IRS-1 and IRS-2 differential signaling in the insulin/insulin-like growth factor-I pathways in fetal brown adipocytes

In the present study we have investigated the contribution of the insulin receptor substrate proteins (IRS-1 and IRS-2) to the insulin/insulin like growth factor I (IGF-I)-signaling pathways in fetal rat brown adipocytes, a model that expresses both insulin and IGF-I receptors. Insulin/IGF-I rapidly stimulated IRS-1 and IRS-2 tyrosine phosphorylation, their association with p85alpha, and IRS-1- and IRS-2-associated phosphatidylinositol (PI) 3-kinase activation to the same extent, the effect of insulin being stronger than the effect of IGF-I at the same physiological dose (10 nM). Furthermore, insulin/IGF-I stimulated IRS-1-associated Grb-2 phosphorylation. However, IRS-2-associated Grb-2 phosphorylation was barely detected. Pull-down experiments with glutathione-S-transferase-fusion proteins containing SH2-domains of p85alpha revealed a strong association between IRS-1 and IRS-2 with p85alpha in response to insulin/IGF-I, the insulin effect being stronger than IGF-I. However, the Grb-2-SH2 domain showed functional differences. While a strong association between IRS-1/Grb-2 was found, IRS-2/Grb-2 association was virtually absent in response to insulin/IGF-I, as also demonstrated in competition studies with a phosphopeptide containing the phosphotyrosine 895 residue within the putative Grb-2-binding domain. Finally, insulin/IGF-I stimulated tyrosine phosphorylation of the three SHC proteins (46, 52, and 66 kDa). Moreover, insulin/IGF-I markedly increased the amount of Grb-2-associated SHC proteins by the same extent. Our results suggest that both IRS-1 and IRS-2 are required for phosphatidylinositol 3-kinase activation that leads to adipogenic and thermogenic differentiation of fetal brown adipose tissue; meanwhile, IRS-1 and SHC, but not IRS-2, associate with Grb-2 leading to the ras-mitogen-activated protein kinase-signaling pathway required for fetal brown adipocyte proliferation.     

Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia

PURPOSE: The identification of immunophenotypic aberrancies through multiparametric flow cytometry makes the differentiation between normal and leukemic cells relatively simple and quick, and is therefore an attractive method for the investigation of minimal residual disease (MRD). In this report, we have analyzed the impact on relapse and relapse-free survival (RFS) of detecting immunophenotypical aberrant cells in acute lymphoblastic leukemia (ALL) patients in cytomorphologic complete remission (CR). MATERIALS AND METHODS: Two hundred eleven bone marrow (BM) samples from 53 consecutive ALL (37 precursor B-ALL and 16 T-ALL) patients were analyzed. The only selection criteria were to have at least one aberrant immunophenotypic feature at diagosis and to have achieved cytomorphologic CR after induction therapy. For MRD detection, all follow-up samples were analyzed with triple labelings using a two-step acquisition procedure, in which 106 cells were screened for the possible persistence of residual leukemic cells with the same phenotypic aberrancy as that identified diagnosis. RESULTS: Patients who displayed a gradual increase in MRD levels showed a higher relapse rate (90% v22%; P < .00001) and shorter median RFS (12 months v not reached; P < .0001) than those with stable or decreasing MRD levels. This adverse prognostic influence also was observed when children and adults, as well as B-ALL and T-ALL patients, were analyzed separately. An MRD level > or = or greater than 10(-3) discriminated two risk groups of ALL patients with significantly different relapse rates and RFS at all treatment phases (end of induction, consolidation, maintenance, and out of treatment). CONCLUSION: Multiparametric flow cytometry of MRD in ALL patients is a valuable tool for relapse prediction and for the identification of a cohort of patients with very poor prognosis.     

Structure–function relationships of fullerene esters in polymer solar cells: unexpected structural effects on lifetime and efficiency

We report both transport measurements and spectroscopic data of polymer/fullerene blend photovoltaics using a small library of fullerene esters to correlate device properties with a range of functionality and structural diversity of the ester substituent. We observe that minor structural changes can lead to significant and surprising differences in device efficiency and lifetime. For example we have found that isomeric R‐groups in the fullerene ester‐based devices we have studied have dramatically different efficiencies. The characteristic lifetimes derived from both transport and spectroscopic measurements are generally comparable; however, some more rapid effects in specific fullerene esters are not observed spectroscopically. It is apparent from our results that each fullerene derivative requires re‐optimization to reveal the best device performance. Furthermore we conclude that a library approach is essential for evaluating the effects of structural differences in the constituent molecules and serves as important device optimization method that is not being currently employed in photovoltaic investigations. Copyright © 2015 John Wiley & Sons, Ltd.     

Influence of the synthesis method on electrical storage capacity of graphene-related materials

ABSTRACT

The electrochemical properties and their relationship with the physico-chemical properties of graphene-based materials have been studied. Graphite was used as the raw material and it was oxidised and then reduced by two alternative approaches, namely thermal and multi-step reduction using ascorbic acid. It was demonstrated that the physico-chemical characteristics of the material are directly related to the synthesis method and greatly influence the major capacitance of the material. It was observed that the materials with lower levels of functional oxygen groups and with a more ordered structure, i.e. similar to graphene powder, are the ideal candidates for use in electrochemical applications as these materials have better capacitance and specific capacitances.     

Study of the growth of infrared-transparent non-spheric layer lenses by continuous-wave laser deposition

The fabrication of non-spheric microns-thick layer lenses by continuous-wave laser deposition has been monitored by using an interferometric method. An infrared-transparent amorphous chalcogenide alloy has been used as base material. Results evidence the thermodynamic nature of this laser-assisted deposition process, with two distinct stages occurring in the deposition rates, namely, a first induction stage with thickness increasing at non-constant rate, and a second steady-state stage with thickness increasing at constant rate. The deposition process has been shown to be reproducible and it allows the tailoring of the thickness profile for promising fabrication of non-spheric layer lenses and free-form optics.     

In vivo quantification of response to treatment in patients with multiple myeloma by <Superscript>1</Superscript>H magnetic resonance spectroscopy of bone marrow

Object Magnetic resonance imaging (MRI) is the gold standard non-invasive technique to detect malignant disease in the bone marrow. Proton magnetic resonance spectroscopy (MRS) can be performed as a quick adjunct to routine spinal MRI. We performed proton MRS to patients with multiple myeloma (MM) at diagnosis and after treatment to investigate the possible correlation of MRS data with response to therapy. Patients and methods Twenty-one patients with newly diagnosed MM underwent combined MRI/MRS explorations of a transverse center section in the fifth lumbar vertebral body. MRS was acquired with STEAM and 40 ms TE. Areas of unsuppressed water and lipid resonances were used to calculate the lipid-to-water ratio (LWR). Results No association was detected between initial LWRs and the clinical characteristics of patients. Post treatment MRS was available in 16 patients of whom 11 (69%) presented an LWR increase, this included all complete responders (8/8, 100%, P = 0.012). A post-treatment LWR value equal to or larger than one is proposed as a non-invasive marker of complete response to treatment. Conclusion Only patients responding to treatment presented a significant increase in bone marrow LWR after therapy. MRS may provide an adequate quantification of response to chemotherapy in patients with MM.     

Improved reverse recovery of self-adaptingp emitter efficiency diodes (SPEED)

Contents A fastpnn ⁺ power diode is described, which due to a self-adaptingp emitter efficiency shows an essentially improved reverse recovery behaviour. Thep emitter consists of ap ⁺ region with high injection efficiency and of ap region which has low injection efficiency and densely intersperses thep ⁺ region. The lateral extension of thep ⁺ areas between thep elements and the vertical doping profile of thep region are chosen in such a manner, that the high efficiency of thep ⁺ region becomes effective only at high currents, reducing the forward voltage drop. Up to the normal operative forward current the carrier concentration at the anode side of the base region is smaller than near thenn ⁺ junction. By commutation, this results in a strong reduction of the peak reverse current and a significantly softer reverse current decay compared with standard diodes designed for the same forward and blocking voltages. Modeling calculations as well as measurements on the operation principle and switching behaviour are presented.

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Verbessertes Rückwärtserholungsverhalten von Dioden mit sich selbst anpassenderp-Emitter Efficiency

Übersicht Es wird eine schnellepnn ⁺-Leistungsdiode beschrieben, deren Rückwärtserholungsverhalten (Recovery-Verhalten) infolge einer sich selbst anpassendenp-Emitter Efficiency stark verbessert ist. Diep-Zone besteht aus einemp ⁺-Bereich mit hohem Emitterwirkungsgrad und einemp-Bereich mit niedrigem Injektionsvermögen der denp ⁺-Bereich dicht durchsetzt. Die laterale Ausdehnung derp ⁺-Gebiete zwischen denp-Teillen sowie das vertikale Dotierungsprofil desp-Bereichs werden so, gewählt, daß der hohe Emitterwirkungsgrad desp ⁺-Bereichs erst bei hohen Strömen wirksam wird und die Durchlaßspannung verkleinert. Bis zum üblichen betriebsmäßigen Durchlaßstrom ist die Ladungsträgerkonzentration an der Anodenseite der Basis kleiner als amnn ⁺-Übergang. Dies führt beim Kommutieren zu einer starken Verkleinerung der Rückstromspitze und einem wesentlich weicheren Abfall des Rückstroms (Soft-Recovery-Verhalten) als bei üblichen schnellen Dioden gleicher Durchlaß- und Sperrspannung. Simulationsrechnungen wie auch Meßergebnisse zur Wirkungsweise und zum Schaltverhalten werden vorgestellt.