On Optimization over the Efficient Set in Linear Multicriteria Programming

The efficient set of a linear multicriteria programming problem can be representedby a reverse convex constraint of the form g(z) ≤ 0, where g is a concavefunction. Consequently, the problem of optimizing some real function over the efficientset belongs to an important problem class of global optimization called reverseconvex programming. Since the concave function used in the literature is only definedon some set containing the feasible set of the underlying multicriteria programmingproblem, most global optimization techniques for handling this kind of reverse convexconstraint cannot be applied. The main purpose of our article is to present amethod for overcoming this disadvantage. We construct a concave function which isfinitely defined on the whole space and can be considered as an extension of the existingfunction. Different forms of the linear multicriteria programming problem arediscussed, including the minimum maximal flow problem as an example

Fluorescence microscopy visualization of halomucin, a secreted 927 kDa protein surrounding Haloquadratum walsbyi cells

At the time of its first publication, halomucin from Haloquadratum walsbyi strain HBSQ001 was the largest archaeal protein known (9159 aa). It has a predicted signal sequence, making it likely to be an extracellular or secreted protein. Best BLAST matches were found to be mammalian mucins that protect tissues to dehydration and chemical stress. It was hypothesized that halomucin participates in protection against desiccation by retaining water in a hull around the halophilic organisms that live at the limits of water activity. We visualized Halo quadratum cells by staining their intracellular polyhydroxybutyrate granules using Nile Blue. Halomucin was stained by immunofluorescence with antibodies generated against synthetic peptides derived from the halomucin amino acid sequence. Polyhydroxybutyrate stained cells were reconstructed in 3D which highlights not only the highly regular square shape but also the extreme flatness of Haloquadratum. Double-staining proves halomucin to be extracellular but to be only loosely associated to cells in agreement with its hypothesized function

The repertory of bone marrow progenitor cells associated with lymphogenic metastasis in patients with invasive carcinoma of no special type

The high mortality of patients with breast cancer is determined by metastatic disease. It is thought that the metastatic disease development associated with the repertory of bone marrow progenitor cells in breast cancer patients. In our study the correlation between the bone marrow progenitor cells presences in the tumor and blood of patients and the lymphogenic metastasis development was studied. The main clinical and pathological parameters of 24 patients with invasive breast carcinoma of non-specific type were analyzed. Endothelial progenitor cells, mesenchymal stem cells, macrophage precursors, hematopoietic progenitor cells were detected with specific antibodies against CD34, CD133, CD90, VEGFR1, CD11b, CD45, CD202 in the cell-rich fluid from frozen tumor. The amount of MCP-1 in the patients blood serum was assessed by enzymelinked immunosorbent assay (ELISA), at a wavelength of 450 nm. The cytokines concentration was calculated from the calibration plot. The program package Statistica 10.0. was used for statistical data processing. The high risk of lymphogenic metastasis in patients who didn't complete a neoadjuvant chemotherapy course was associated with the number of HPC, EPC and MSC in tumor and MCP-1 in blood

Reciprocal regulation of PKA and rac signaling

Activated G protein-coupled receptors (GPCRs) and receptor tyrosine kinases relay extracellular signals through spatial and temporal controlled kinase and GTPase entities. These enzymes are coordinated by multifunctional scaffolding proteins for precise intracellular signal processing. The cAMP-dependent protein kinase A (PKA) is the prime example for compartmentalized signal transmission downstream of distinct GPCRs. A-kinase anchoring proteins tether PKA to specific intracellular sites to ensure precision and directionality of PKA phosphorylation events. Here, we show that the Rho-GTPase Rac contains A-kinase anchoring protein properties and forms a dynamic cellular protein complex with PKA. The formation of this transient core complex depends on binary interactions with PKA subunits, cAMP levels and cellular GTP-loading accounting for bidirectional consequences on PKA and Rac downstream signaling. We show that GTP-Rac stabilizes the inactive PKA holoenzyme. However, β-adrenergic receptor-mediated activation of GTP-Rac–bound PKA routes signals to the Raf-Mek-Erk cascade, which is critically implicated in cell proliferation. We describe a further mechanism of how cAMP enhances nuclear Erk1/2 signaling: It emanates from transphosphorylation of p21-activated kinases in their evolutionary conserved kinase-activation loop through GTP-Rac compartmentalized PKA activities. Sole transphosphorylation of p21-activated kinases is not sufficient to activate Erk1/2. It requires complex formation of both kinases with GTP-Rac1 to unleash cAMP-PKA–boosted activation of Raf-Mek-Erk. Consequently GTP-Rac functions as a dual kinase-tuning scaffold that favors the PKA holoenzyme and contributes to potentiate Erk1/2 signaling. Our findings offer additional mechanistic insights how β-adrenergic receptor-controlled PKA activities enhance GTP-Rac–mediated activation of nuclear Erk1/2 signaling

The PANDA GEM-based TPC Prototype

We report on the development of a GEM-based TPC prototype for the PANDA experiment. The design and requirements of this device will be illustrated, with particular emphasis on the properties of the recently tested GEM-detector, the characterization of the read-out electronics and the development of the tracking software that allows to evaluate the GEM-TPC data.Comment: submitted to NIMA 4 pages, 6 picture

Закономерности изменения физико-механических свойств сплава Zr-1%Nb при комплексном ионно-плазменном модифицировании поверхности и наводороживании

В работе были изучены особенности изменения морфологии, структуры и физико-механических свойств циркониевого сплава Zr-1%Nb, подвергнутого комплексному ионно-плазменному модифицированию поверхности методами плазменно-иммерсионной ионной имплантации титана и осаждения покрытий нитрида титана. Показана высокая эффективность защиты сформированных структур от проникновения водорода в циркониевый сплав. Изучены механизмы сорбции и захвата водорода в титансодержащем модифицированном слое.In the present work, the features of the change in the morphology, structure, and physico-mechanical properties of zirconium alloy Zr-1%Nb subjected to complex ion-plasma surface modification by the methods of plasma-immersion titanium ion implantation and deposition of titanium nitride coatings were studied. The high protective properties of the formed structures against hydrogen permeation into the zirconium alloy is shown. Mechanisms of sorption and capture of hydrogen in a titanium-doped modified layer are studied

A solid‐phase transfection platform for arrayed CRISPR screens [Corrigendum]

Since the publication of this study, it has come to our attention that a citation to the study by Bulkescher et al (2017) was omitted from the Introduction. The following sentence should have been included in the introduction: “A previously reported solid‐phase reverse transfection method for proteins (Bulkescher et al , 2017) was used for the delivery of RNPs for three endogenous genes suggesting the potential of solid‐phase reverse transfection for CRISPR/Cas9‐based gene editing, despite its low efficiency”. We apologise for any inconvenience this omission may have caused

A solid-phase transfection platform for arrayed CRISPR screens

Arrayed CRISPR‐based screens emerge as a powerful alternative to pooled screens making it possible to investigate a wide range of cellular phenotypes that are typically not amenable to pooled screens. Here, we describe a solid‐phase transfection platform that enables CRISPR‐based genetic screens in arrayed format with flexible readouts. We demonstrate efficient gene knockout upon delivery of guide RNAs and Cas9/guide RNA ribonucleoprotein complexes into untransformed and cancer cell lines. In addition, we provide evidence that our platform can be easily adapted to high‐throughput screens and we use this approach to study oncogene addiction in tumor cells. Finally demonstrating that the human primary cells can also be edited using this method, we pave the way for rapid testing of potential targeted therapies