Mechanism of Anticancer Action of Novel Imidazole Platinum(II) Complex Conjugated with G2 PAMAM-OH Dendrimer in Breast Cancer Cells

Transition metal coordination compounds play an important role in the treatment of neoplastic diseases. However, due to their low selectivity and bioavailability, as well as the frequently occurring phenomenon of drug resistance, new chemical compounds that could overcome these phenomena are still being sought. The solution seems to be the synthesis of new metal complexes conjugated with drug carriers, e.g., dendrimers. Numerous literature data have shown that dendrimers improve the bioavailability of the obtained metal complexes, solving the problem of their poor solubility and stability in an aqueous environment and also breaking down inborn and acquired drug resistance. Therefore, the aim of this study was to synthesize a novel imidazole platinum(II) complex conjugated with and without the second-generation PAMAM dendrimer (PtMet2–PAMAM and PtMet2, respectively) and to evaluate its antitumor activity. Cell viability studies indicated that PtMet2–PAMAM exhibited higher cytotoxic activity than PtMet2 in MCF-7 and MDA-MB-231 breast cancer cells at relatively low concentrations. Moreover, our results indicated that PtMet2–PAMAM exerted antiproliferative effects in a zebrafish embryo model. Treatment with PtMet2–PAMAM substantially increased apoptosis in a dose-dependent manner via caspase-9 (intrinsic pathway) and caspase-8 (extrinsic pathway) activation along with pro-apoptotic protein expression modulation. Additionally, we showed that apoptosis can be induced by activating POX, which induces ROS production. Furthermore, our results also clearly showed that the tested compounds trigger autophagy through p38 pathway activation and increase Beclin-1, LC3, AMPK, and mTOR inhibition. The high pro-apoptotic activity and the ability to activate autophagy by the imidazole platinum(II) complex conjugated with a dendrimer may be due to its demonstrated ability to reverse multidrug resistance (MDR) and thereby increase cellular accumulation in breast cancer cells.     

3GPP LTE‐Assisted Wi‐Fi‐Direct: Trial Implementation of Live D2D Technology

This paper is a first‐hand summary on our comprehensive live trial of cellular‐assisted device‐to‐device (D2D) communications currently being ratified by the standards community for next‐generation mobile broadband networks. In our test implementation, we employ a full‐featured 3GPP LTE network deployment and augment it with all necessary support to provide real‐time D2D connectivity over emerging Wi‐Fi‐Direct (WFD) technology. As a result, our LTE‐assisted WFD D2D system enjoys the required flexibility while meeting the existing standards in every feasible detail. Further, this paper provides an account on the extensive measurement campaign conducted with our implementation. The resulting real‐world measurements from this campaign quantify the numerical effects of D2D functionality on the resultant system performance. Consequently, they shed light on the general applicability of LTE‐assisted WFD solutions and associated operational ranges.     

Monolithic ZnTe-based pillar microcavities containing CdTe quantum dots

Micropillars of different diameters have been prepared by focused ion beam milling out of a planar ZnTe-based cavity. The monolithic epitaxial structure, deposited on a GaAs substrate, contains CdTe quantum dots embedded in a ZnTe λ-cavity delimited by two distributed Bragg reflectors (DBRs). The high refractive index material of the DBR structure is ZnTe, while for the low index material a short-period triple MgTe/ZnTe/MgSe superlattice is used. The CdTe quantum dots are formed by a novel Zn-induced formation process and are investigated by scanning transmission electron microscopy. Micro-photoluminescence measurements show discrete optical modes for the pillars, in good agreement with calculations based on a vectorial transfer matrix method. The measured quality factor reaches a value of 3100.     

Long-range surface plasmon-enhanced fluorescence spectroscopy biosensor for ultrasensitive detection of E. coli O157:H7

A new biosensor platform for the detection of bacterial pathogens based on long-range surface plasmon-enhanced fluorescence spectroscopy (LRSP-FS) is presented. The resonant excitation of LRSP modes provides an enhanced intensity of the electromagnetic field, which is directly translated to an increased strength of fluorescence signal measured upon the capture of target analyte at the sensor surface. LRSPs originate from a coupling of surface plasmons across a thin metallic film embedded in dielectrics with similar refractive indices. With respect to regular surface plasmon-enhanced fluorescence spectroscopy, the excitation of LRSPs offers the advantage of a larger enhancement of the evanescent field intensity and a micrometer probing depth that is comparable to the size of target bacterial pathogens. The potential of the developed sensor platform is demonstrated in an experiment in which the detection of E. coli O157:H7 was carried out using sandwich immunoassays. The limit of detection below 10 cfu mL(-1) and detection time of 40 min were achieved.     

A Shallow Text Processing Core Engine

In this article we present SMES–SPPC, a high–performance system for intelligent extraction of structured data from free text documents. SMES–SPPC consists of a set of domain–adaptive shallow core components that are realized by means of cascaded weighted finite–state machines and generic dynamic tries. The system has been fully implemented for German; it includes morphological and on–line compound analysis, efficient POS–filtering, high–performance named–entity recognition and chunk parsing based on a novel divide–and–conquer strategy. The whole approach proved to be very useful for processing free word order languages such as German. SMES–SPPC has a good performance (more than 6000 words per second on standard PC environments) and achieves high linguistic coverage, especially for the divide–and–conquer parsing strategy, where we obtained an f –measure of 87.14% on unseen data.     

Positive effects of allosteric modulators on the binding properties and the function of muscarinic acetylcholine receptors

Data are reviewed indicating that allosteric modulators can enhance the affinities of muscarinic receptors for their antagonists and agonists, that the enhancement of the affinity for agonists is relevant functionally, and that the allosterically induced conformational change also affects the interaction between the receptors and the G proteins.     

Identifying the cutting tool type used in excavations using neural networks

The paper presents results of preliminary research on utilising neural networks to identify excavating cutting tool’s type used in multi-tool excavating heads of mechanical coal miners. Such research is necessary to identify rock excavating process with a given head, and construct adaptation systems for control of excavating process with such a head.     

Torsion classes of <Emphasis Type="Italic">MV</Emphasis>-algebras

 Torsion classes of MV-algebras are defined as radical classes which are closed with respect to homomorphisms; in this paper we investigate their relations to radical classes of lattice ordered groups and to varieties of MV-algebras. Supported by Grant VEGA 1/9056/02.     

Electronegativity Equalization Method: Parameterization and Validation for Large Sets of Organic,Organohalogene and Organometal Molecule

The Electronegativity Equalization Method (EEM) is a fast approach for charge calculation. A challenging part of the EEM is the parameterization, which is performed using ab initio charges obtained for a set of molecules. The goal of our work was to perform the EEM parameterization for selected sets of organic, organohalogen and organometal molecules. We have performed the most robust parameterization published so far. The EEM parameterization was based on 12 training sets selected from a database of predicted 3D structures (NCI DIS) and from a database of crystallographic structures (CSD). Each set contained from 2000 to 6000 molecules. We have shown that the number of molecules in the training set is very important for quality of the parameters. We have improved EEM parameters (STO-3G MPA charges) for elements that were already parameterized, specifically: C, O, N, H, S, F and Cl. The new parameters provide more accurate charges than those published previously. We have also developed new parameters for elements that were not parameterized yet, specifically for Br, I, Fe and Zn. We have also performed crossover validation of all obtained parameters using all training sets that included relevant elements and confirmed that calculated parameters provide accurate charges.