T-cell Receptor Is a Threshold Detector: Sub- and Supra-Threshold Stochastic Resonance in TCR-MHC Clusters on the Cell Surface.

Stochastic resonance in clusters of major histocompatibility molecules is extended by a more detailed description of adaptive thresholding and by applying the notion of suprathreshold stochastic resonance as a stochastically quantizing encoder of transmembrane signaling downstream of major histocompatibility molecules and T-cell receptors on the side of presenting and recognizing cells, respectively. The adaptive nature of thresholding is partly explained by a mirroring of the noncognate-cognate dichotomy shown by the T-cell receptor structure and the kinetic-segregation model of the onset of T-cell receptor triggering. Membrane clusters of major histocompatibility molecules and T-cell receptors on their host cells are envisioned as places of the temporal encoding of downstream signals via the suprathreshold stochastic resonance process.

Adaptive threshold-stochastic resonance (AT-SR) in MHC clusters on the cell surface.

Highly conserved 2D receptor clusters (membrane rafts) of immunological signaling molecules with MHCI and MHCII antigens as their cores have been observed in the past on the surface of T- and B-cell lines of lymphoid origin, as well as on cells from patients with colon tumor and Crohn's disease. Conservativity is related to the ever presence of MHCI molecules. Although they are suspected to play a role in maintaining these clusters and facilitating transmembrane signaling, their exact role has been left largely enigmatic.

Dual-Laser Tetra-Polarization FRET (4polFRET) for Site-Selective Control of Homo-FRET in Hetero-FRET Systems on the Cell Surface: The Homo-FRET Gate.

The effects of donor homo-Förster resonance energy transfer (homo-FRET) taking place in hetero-FRET systems is described in the context of hetero-FRET detection via donor and acceptor fluorescence anisotropies in cell surface receptor clusters. Donor homo-FRET can influence both the efficiency of detection as well as the magnitude of the detectable hetero-FRET. A 4-fold polarized FRET detection scheme-tetrapolarization FRET (4polFRET)-is proposed not only for discriminating the effects of homo-FRET from those of hetero-FRET, but also for correlating homo-associations of the donors and acceptors at different donor-acceptor distances, even beyond the critical Förster distance for hetero-FRET ( R).

Checkpoint for helicity conservation in fluorescence at the nanoscale: Energy and helicity transfer (hFRET) from a rotating donor dipole.

Orientation factor (κ) for FRET from a rotating donor dipole, transferred helicity of the donor field and torque exerted on the acceptor by the donor have been investigated in the framework of classical electrodynamics. It is shown that for rotating dipole, κ is significantly higher as compared to linear dipole independently of the orientation distribution of the donor and acceptor and whether the static or the dynamic rotational regimes are used for averaging κ. By this property of κ, FRET serves as an example for a phenomenon where local field interference may take place in a "natural" way for emitters possessing rotating dipoles in their excited states by nature.

Confocal microscopic dual-laser dual-polarization FRET (2polFRET) at the acceptor side for correlating rotations at different distances on the cell surface.

Relationship of donor and acceptor fluorescence anisotropies as well as efficiency of fluorescence resonance energy transfer (FRET) has been investigated in a confocal microscope in the context of FRET systems comprised of donor and acceptor-labeled MHCI and MHCII receptors on the surface of Kit-225 K6 human T-cells. The measurements have been carried out in a 2-laser, 5-signal platform where the total donor fluorescence intensity and 2 acceptor fluorescence intensities with their anisotropies - one at the donor's excitation wavelength, the other at the acceptor's excitation wavelength - have been detected. This configuration enabled the determination of FRET efficiency and correlating it with the two acceptor fluorescence anisotropies as a kind of calibration.

Long-term Efficacy, Safety, and Immunogenicity of Biosimilar Infliximab After One Year in a Prospective Nationwide Cohort.

Background: It has been previously shown that biosimilar infliximab CT-P13 is effective and safe in inducing remission in inflammatory bowel diseases. We report here the 1-year outcomes from a prospective nationwide inflammatory bowel disease cohort.

Methods: A prospective, nationwide, multicenter, observational cohort was designed to examine the efficacy and safety of CT-P13 in the induction and maintenance treatment of Crohn's disease (CD) and ulcerative colitis (UC).

Frequency and characteristics of infusion reactions during biosimilar infliximab treatment in inflammatory bowel diseases: results from Central European nationwide cohort.

Background: Safety data of the 'real life' use of an infliximab biosimilar, CT-P13 in inflammatory bowel disease (IBD) are still lacking. Our aim was to assess the frequency and characteristics of infusion reactions during CT-P13 therapy in 13 Hungarian and 1 Czech IBD centres.

Methods: Clinical and safety data was registered at fixed appointments.

Sensitivity of Helicobacter pylori detection by Giemsa staining is poor in comparison with immunohistochemistry and fluorescent in situ hybridization and strongly depends on inflammatory activity.

Background: Conventional stainings (including H&E and special stains like Giemsa) are the most widely applied histopathologic detection methods of Helicobacter pylori (HP).

Materials And Methods: We aimed to compare the diagnostic performance of Giemsa staining with immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) on a monocentric cohort of 2896 gastric biopsies and relate results to histologic alterations in order to find such histopathologic subgroups in which these methods underperform. All cases were categorized regarding presence or absence of chronic gastritis, inflammatory activity, and mucosal structural alterations.

Prediction of Short- and Medium-term Efficacy of Biosimilar Infliximab Therapy. Do Trough Levels and Antidrug Antibody Levels or Clinical And Biochemical Markers Play the More Important Role?

Background And Aims: Biosimilar infliximab CT-P13 received European Medicines Agency [EMA] approval in June 2013 for all indications of the originator product. In the present study, we aimed to evaluate the predictors of short- and medium-term clinical outcome in patients treated with the biosimilar infliximab at the participating inflammatory bowel disease [IBD] centres in Hungary.

Methods: Demographic data were collected and a harmonised monitoring strategy was applied.

[Invasive methods in the treatment of obesity].

Treatment of obesity and concomitant diseases have a significant burden on the health care system. Due to the lack of efficacy of conservative treatment methods, attention has shifted towards invasive methods. Surgical and endoscopic treatments of obesity are based on two different methods: restrictive and malabsorptive procedures or their combination.

Perrin and Förster unified: Dual-laser triple-polarization FRET (3polFRET) for interactions at the Förster-distance and beyond.

Dual laser flow cytometric energy transfer (FCET)--elaborated by Trón et al. in 1984--is an efficient and rapid way of measuring FRET on large cell populations. FRET efficiency and the donor and acceptor concentrations are determined from one donor and two acceptor signals.

Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort.

Background And Aims: Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking.

Methods: A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn's disease [CD] and ulcerative colitis [UC].

Depolarized FRET (depolFRET) on the cell surface: FRET control by photoselection.

Sensitivity of FRET in hetero- and homo-FRET systems on the photoselected orientation distribution of donors has been proven by using polarized and depolarized light for excitation. FRET as well as donor and acceptor anisotropies have been simultaneously measured in a dual emission-polarization scheme realized in a conventional flow cytometer by using single laser excitation and applying fluorophore-conjugated mAbs against the MHCI and MHCII cell surface receptors. Depolarization of the originally polarized light have been achieved by using crystal depolarizers based on Cornu's principle, a quarter-wave plate for circular polarization, and a parallel beam splitter acting as a diagonal-polarizer for dual-polarization excitation.

Dual-laser homo-FRET on the cell surface.

Inhomogeneous broadening and red-edge effects have been detected on a highly mobile system of fluorescently conjugated mAbs targeted to cell surface receptors. By exploiting site-selective spectroscopy and the characteristic loss of homo-FRET on increasing excitation and decreasing emission wavelengths, contributions of physical rotation and homo-FRET to the depolarization of fluorescence anisotropy have been separated. Absolute homo-FRET efficiency has been determined by ratioing two anisotropies: a homo-FRET-sensitive one, which is excited at the absorption main band and detected at the long wavelength region of emission, and a homo-FRET-insensitive one, which is excited at the long wavelength region of absorption and detected at the short wavelength region of emission.

Single-laser polarization FRET (polFRET) on the cell surface.

A new method for the simultaneous detection of rotational mobility and proximity of cell surface receptors is presented based on cell-by-cell basis measurement of polarized fluorescence intensity components of the donor and acceptor of a FRET system. In addition to the FRET efficiency and the donor and acceptor concentrations, the method makes also possible the determination of the rotational characteristics and the associated fraction of the donors (FRET-fraction). The method is illustrated with flow cytometric and rFLIM measurements on donor-acceptor systems comprising fluorescently labeled whole antibodies and their Fab fragments against epitopes of the MHCI and MHCII cell surface receptors on human lymphoblast cells.

Intensity correlation-based calibration of FRET.

Dual-laser flow cytometric resonance energy transfer (FCET) is a statistically efficient and accurate way of determining proximity relationships for molecules of cells even under living conditions. In the framework of this algorithm, absolute fluorescence resonance energy transfer (FRET) efficiency is determined by the simultaneous measurement of donor-quenching and sensitized emission. A crucial point is the determination of the scaling factor α responsible for balancing the different sensitivities of the donor and acceptor signal channels.

Devastating decline of forest elephants in central Africa.

African forest elephants- taxonomically and functionally unique-are being poached at accelerating rates, but we lack range-wide information on the repercussions. Analysis of the largest survey dataset ever assembled for forest elephants (80 foot-surveys; covering 13,000 km; 91,600 person-days of fieldwork) revealed that population size declined by ca. 62% between 2002-2011, and the taxon lost 30% of its geographical range.