BODIPY-Based Photosensitizers as Potential Anticancer and Antibacterial Agents: Role of the Positive Charge and the Heavy Atom Effect

Boron-dipyrromethene derivatives, including cationic and iodinated analogs, were obtained and subjected to physicochemical and in vitro photodynamic activity studies. Iodinated derivatives revealed a substantial heavy atom effect manifested by a bathochromic shift of the absorption band by about 30 nm and fluorescence intensity reduced by about 30–35 times, compared to that obtained for non-iodinated ones. In consequence, singlet oxygen generation significantly increased with Φ_Δ values in the range 0.69–0.97. The in vitro photodynamic activity was evaluated on Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and on human androgen-sensitive prostate adenocarcinoma cells (LNCaP). The novel cationic, iodinated BODIPY, demonstrated the highest activity toward all studied cells. An excellent cytotoxic effect was found against LNCaP cells with an IC₅₀ value of 19.3 nM, whereas the viability of S. aureus was reduced by >5.6 log₁₀ at 0.25 μM concentration and by >5.3 log₁₀ in the case of E. coli at 5 μM. Thus, this analog seems to be a very promising candidate for the application in both anticancer and antimicrobial photodynamic therapy.     

An integrated LC-ESI-MS platform for quantitation of serum peptide ladders. Application for colon carcinoma study

Mounting evidence indicates that MS analysis of the human blood peptidome allows to distinguish between cancer and non-cancer samples, giving promise for a new MS-based diagnostic tool. However, several aspects of already published work have been criticized and demand for more methodical approach has been formulated. Motivated by this we undertook a systematic study of the plasma and serum peptidome using an integrated ESI-LC-MS-based platform, equipped with new data analysis tools for relative and absolute peptide quantitation. We used a high resolution LC-ESI-MS to analyze well-separated MS signals corresponding to peptides, and measured the variability of >1000 peptide signal amplitudes across a set of plasma and serum samples from healthy individuals. By spiking serum samples with known amounts of isotopically labeled versions of a selected set of peptides we measured the variability of their absolute concentration in this sample set and demonstrated a strong influence of clotting time on the concentration of these peptides in serum. Finally, we used this new LC-ESI-MS analytical platform for the differential analysis of healthy versus colon cancer serum samples and found that it was possible to distinguish the two groups with 89.8% sensitivity and 94.6% specificity.     

Remote mobile manipulation with the centauro robot: Full‐body telepresence and autonomous operator assistance

Solving mobile manipulation tasks in inaccessible and dangerous environments is an important application of robots to support humans. Example domains are construction and maintenance of manned and unmanned stations on the moon and other planets. Suitable platforms require flexible and robust hardware, a locomotion approach that allows for navigating a wide variety of terrains, dexterous manipulation capabilities, and respective user interfaces. We present the CENTAURO system which has been designed for these requirements and consists of the Centauro robot and a set of advanced operator interfaces with complementary strength enabling the system to solve a wide range of realistic mobile manipulation tasks. The robot possesses a centaur‐like body plan and is driven by torque‐controlled compliant actuators. Four articulated legs ending in steerable wheels allow for omnidirectional driving as well as for making steps. An anthropomorphic upper body with two arms ending in five‐finger hands enables human‐like manipulation. The robot perceives its environment through a suite of multimodal sensors. The resulting platform complexity goes beyond the complexity of most known systems which puts the focus on a suitable operator interface. An operator can control the robot through a telepresence suit, which allows for flexibly solving a large variety of mobile manipulation tasks. Locomotion and manipulation functionalities on different levels of autonomy support the operation. The proposed user interfaces enable solving a wide variety of tasks without previous task‐specific training. The integrated system is evaluated in numerous teleoperated experiments that are described along with lessons learned.     

Detection of buried reference structures by use of atomic force acoustic microscopy

The miniaturization of micro- and nanoelectronic components requires new methods for the inspection of buried inner structures at the nanoscale. We used the atomic force acoustic microscopy technique (AFAM) to image subsurface defects. This technique combines high lateral resolution with the capability to determine local elastic properties of materials near the surface. As the structures buried near the surface change the effective tip-sample contact stiffness it is possible to detect them. For the verification of the detection capabilities of AFAM we fabricated well-defined buried void structures with different geometries and dimensions. Large, thin, plate like structures of silicon nitride with a local filling were our first test samples. Then, sets of nine small, square, thin plates with thicknesses increasing stepwise from 30 to 270 nm were etched in a thinned silicon wafer. The last two samples contained wedge structures of widths varying between 1.6 and 10 μm. Our results showed that it was possible to detect buried void structures at depths between 180 and 900 nm. We also observed that the depths at which the buried defects can be detected by the use of the AFAM method depend on the defect dimensions and geometry, and on the mismatch in the elastic properties of the sample and the defects. The experimental results obtained for the groups of small, thin plates were verified by quantitative analysis via finite element method (FEM) simulations.     

Methods of Selenium Supplementation: Bioavailability and Determination of Selenium Compounds

Selenium, a “dual-surface” element, maintains a very thin line between a level of necessity and harmfulness. Because of this, a deficiency or excess of this element in an organism is dangerous and causes health-related problems, both physically and mentally. The main source of selenium is a balanced diet, with a proper selection of meat and plant products. Meanwhile, the proper assimilation of selenium into these products depends on their bioavailability, bioaccessibility, and/or bioactivity of a given selenium compound.

From the time when it was discovered that selenium and its compounds have a significant influence on metabolic processes and in many countries throughout the world, a low quantity of selenium was found in different parts of the environment, pressure was put upon an effective and fast method of supplementing the environment with the help of selenium. This work describes supplementation methods applied with the use of selenium, as well as new ideas for increasing the level of this element in various organisms.

Based on the fact that selenium appears in the environment at trace levels, the determination of total amount of selenium or selenium speciation in a given sample demands the selection of appropriate measurement methods. These methods are most often comprised of a sample preparation technique and/or a separation technique as well as a detection system. The work presents information on the subject of analytical methods used for determining selenium and its compounds as well as examples in literature of their application.     

Promising perspectives towards regrowing a human arm

Despite the great enthusiasm about tissue engineering during the 1980s and the many significant basic observations made since then, the clinical application of tissue-engineered products has been limited. However, the prospect of creating new human tissues and organs is still exciting and continues to be a significant challenge for scientists and clinicians. A human arm is an extremely complicated biological construction. Considering regrowing a human arm requires asking about the current state-of-the-art of tissue engineering and the real capabilities that it may offer within a realistic time horizon. This work briefly addresses the state-of-the-art in the fields of cells and scaffolds that have high regenerative potential. Additional tools that are required to reconstruct more complex parts of the body, such as a human arm, seem achievable with the already available more sophisticated culture systems including three-dimensional organization, dynamic conditions and co-cultures. Finally, we present results on cell differentiation and cell and tissue maturation in culture when cells are exposed to mechanical forces. We postulate that in the foreseeable future even such complicated structures such as a human arm will be regrown in full in vitro under the conditions of a mechanically controlled co-culture system.     

Synergic effects of grain refinement and precipitation strengthening

The article describes the combined effects of grain size and second phase particles on mechanical properties of CuCrZr alloy subjected to SPD processing and ageing in two sequences: (i) SPD processing followed by ageing and (ii) SPD processing of samples aged prior to deformation. It was revealed that each of these strengthening mechanisms acting alone gives a significant increase in mechanical strength (5 and 10 times in the case of ageing and SPD processing, respectively). However, it has been found in the present study that the strength of samples subjected to grain refinement and precipitation hardening is not a direct sum of the strengthening brought about by these two strengthening mechanisms acting alone. This finding is discussed in terms of the inter-dependence of grain size–particle strengthening in SPD nano-metals.     

Design of fully active FGF-1 variants with increased stability

Fibroblast growth factor 1 is a powerful mitogen playing an important role in morphogenesis, angiogenesis and wound healing and is therefore of potential medical interest. Using homologous sequence and structure comparisons, we designed and constructed 16 mutants of FGF-1 with increased thermodynamic stability, as determined by chemical and heat denaturation. For multiple mutants, additive effects on stability were observed, providing mutants up to 7.8 degrees C more stable than the wild-type. None of the introduced mutations affected any FGF-1 biological activities, such as stimulation of DNA synthesis, MAP kinase activation and binding to the FGF receptor on the cell surface. Our study provides a good starting point to improve the stability of FGF-1 in the context of its wide potential therapeutic applications. We showed that a homology approach is an effective method to change the thermodynamic properties of the protein without altering its function.     

Total mercury distribution in sediment cores from Kuwait Bay

Five sediment cores from Kuwait Bay were taken in order to study the present distribution of total mercury (THg) in the vicinity of the Salt and Chlorine Plant (SCP) operated in the 1963–1985 period. The THg concentration profiles were also determined in four sediment cores from the northern part of Kuwait Bay. Additionally, average THg contents were measured in the surface layer (40 cm) of five sediment samples in the entrance of Kuwait Bay, in order to compare the present Hg levels in other parts of this reservoir. The cores were dated by ²¹⁰Pb method. The observed contents of mercury were in the range of 35 to 2000 µg/kg dry weight (ppb). Thus, the bottom sediments in these three areas of Kuwait Bay are still contaminated by Hg. In a few cases, the depth concentration profiles of THg were disturbed as an effect of partial mixing of the sediment layers, especially in the shallow, northern part of Kuwait Bay. This suggestion was supported by the results of additional measurements of the anthropogenic ¹³⁷Cs profiles in the same cores.