Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB

Natural products are widely used as source for drugs development. An interesting example is represented by natural drugs developed against human topoisomerase IB, a ubiquitous enzyme involved in many cellular processes where several topological problems occur due the formation of supercoiled DNA. Human topoisomerase IB, involved in the solution of such problems relaxing the DNA cleaving and religating a single DNA strand, represents an important target in anticancer therapy. Several natural compounds inhibiting or poisoning this enzyme are under investigation as possible new drugs. This review summarizes the natural products that target human topoisomerase IB that may be used as the lead compounds to develop new anticancer drugs. Moreover, the natural compounds and their derivatives that are in clinical trial are also commented on.     

Cardiovascular adjustments to high- and low-intensity exercise do not regulate temporary threshold shifts

Sixteen adults cycled for 10 min at low and high intensities--with and without noise. The noise consisted of a 1/3 octave band-filtered noise with a 2,000 Hz center frequency at 104 dB SPL. Regardless of whether or not noise was present, systolic blood pressure increased 14% and 40% above rest during low- and high-intensity exercise, respectively. Heart rate also increased above rest (36% and 90%) during low- and high-intensity exercise, respectively. Temporary threshold shifts (TTS) at 3,000, 4,000 and 6,000 Hz could not be differentiated following low- and high-intensity exercise when noise was not present. We report significant TTS at the three frequencies following 10 min of noise exposure with or without low- or high-intensity exercise. TTS was not influenced by either the 14-40% increase in blood pressure or the 36-90% increase in heart rate induced by exercise. The inability of noise alone to influence either blood pressure or heart rate appears to implicate systems other than the cardiovascular in the regulation of hearing sensitivity.     

The toxicology and prevention of the risks of occupational exposure to aromatic polycyclic hydrocarbons. I. Guide lines for the prevention of the risks of occupational exposure to aromatic polycyclic hydrocarbons. Società Italiana Valori di Riferimento and Cattedra di Medicina del Lavoro, Università di Brescia]

AIM: Patients with various disorders of gastric function were studied with radiolabeled test meals of different consistency to elaborate the effect of ingested media on gastric peristalsis and emptying. METHODS: In 12 patients parameters of gastric function were intraindividually compared after ingestion of a semiliquid and a solid test meal. In addition to the standard evaluation derived from time activity curves condensed images were established from two fixed time intervals (early and late period). These images were used to evaluate the amplitude and frequency of gastric contractions using Fourier analysis. RESULTS: As expected gastric emptying was influenced by the consistency of the test meal. Mean emptying rates for the solid meal were significant lower than those for the semiliquid one (p < 0.01). The amplitude and frequency of gastric contractions, however, did not depend on the consistency of the test meal. Within the course of the examination contraction amplitudes significantly increased (p < 0.05) from the early to the late period using both, solid as well as semiliquid test meals. The frequency of gastric contractions remained unchanged. CONCLUSION: As shown by an intraindividual data comparison amplitude and frequency of gastric contractions seem to be independent of the consistency of ingested test meals whereas gastric emptying is significantly influenced by the administered media. Semiliquid meals offer advantages with respect to the shorter examination time and simpler preparation and therefore may be preferred for routine use. Since amplitudes seem to vary within the observation period standardized acquisition protocols are recommended for the evaluation of this parameter.     

A multi-objective sequential method for manufacturing cost and structural optimization of modular steel towers

This paper proposes a methodological approach for the multi-objective optimization of steel towers made from prefabricated cylindrical stacks that are typically used in the oil and gas sector. The goal is to support engineers in designing economical products while meeting structural requirements. The multi-objective optimization approach involves the minimization of the weights and costs related to the manufacturing and assembly phases. The method is based on three optimization levels. The first is used in the preliminary design phase when a company receives a request for proposal. Here, minimal information on the order is available, and the time available to formulate an offer is limited. Thus, parametric cost models and simplified 1-D geometries are used in the optimization loop performed by genetic algorithms. The second phase, the embodiment design phase, starts when an offer becomes an order based on the results of the first stage. Simplified shell geometries and advanced parametric cost models are used in the optimization loop, which present a restricted problem domain. In the last phase involving detailed design, a full 3-D computer-aided design model is generated, and specific finite-element method simulations are performed. The cost estimations, given the high levels of detail considered, are analytic and are performed using dedicated software.     

From learning to new goal generation in a bioinspired robotic setup

In the field of cognitive bioinspired robotics, we focus on autonomous development, and propose a possible model to explain how humans generate and pursue new goals that are not strictly dictated by survival. Autonomous lifelong learning is an important ability for robots to make them able to acquire new skills, and autonomous goal generation is a basic mechanism for that. The Intentional Distributed Robotic Architecture (IDRA) here presented intends to allow the autonomous development of new goals in situated agents starting from some simple hard-coded instincts. It addresses this capability through an imitation of the neural plasticity, the property of the cerebral cortex supporting learning. Three main brain areas are involved in goal generation, cerebral cortex, thalamus, and amygdala; these are mimicked at a functional level by the modules of our computational model, namely Deliberative, Working-Memory, Goal-Generator, and Instincts Modules, all connected in a network. IDRA has been designed to be robot independent; we have used it in simulation and on the real Aldebaran NAO humanoid robot. The reported experiments explore how basic capabilities, as active sensing, are obtained by the architecture.     

Layered Germanium Hybrid Perovskite Bromides: Insights from Experiments and First‐Principles Calculations

Metal halide perovskites are maturing as materials for efficient, yet low cost solar cells and light‐emitting diodes, with improving operational stability and reliability. To date however, most perovskite‐based devices contain Pb, which poses environmental concerns due to its toxicity; lead‐free alternatives are of importance to facilitate the development of perovskite‐based devices. Here, the germanium‐based Ruddledsen–Popper series (CH₃(CH₂)₃NH₃)₂(CH₃NH₃)_n?1Ge_nBr_3n+1 is investigated, derived from the parent 3D (n = ∞) CH₃NH₃GeBr₃ perovskite. Divalent germanium is a promising, nontoxic alternative to Pb²⁺ and the layered, 2D structure appears promising to bolster light emission, long‐term durability, and moisture tolerance. The work, which combines experiments and first principle calculations, highlights that in germanium bromide perovskites the optical bandgap is weakly affected by 2D confinement and the highly stereochemically active 4s² lone pair preludes to possible ferroelectricity, a topic still debated in Pb‐containing compounds.     

Solid-State Synthesis of Ultrafine BaTiO3 Powders from Nanocrystalline BaCO3 and TiO2

Barium titanate has been prepared by solid-state reaction of nanocrystalline TiO₂ (70 nm) with BaCO₃ of different particle size (650, 140, and 50 nm). The results give evidence of a strong effect of the size of BaCO₃ in the solid-state synthesis of barium titanate. The use of nanocrystalline BaCO₃ already leads to formation of the single-phase BaTiO₃ after calcination for 8 h at 800°C. The final powder consists of primary particles of ≈100 nm, has a narrow particle size distribution with d ₅₀=270 nm, and no agglomerates larger than 800 nm. For the coarser carbonate, 4 h calcination at 1000°C are required and the final powder is much coarser. Solid-state reaction of nanocrystalline BaCO₃ and TiO₂ represents an alternative to chemical preparation routes for the production of barium titanate ultrafine powders.     

Reduction of Lung Metastases by Na[trans-RuCl(4)(DMSO)Im] is not Coupled With the Induction of Chemical Xenogenization

The effects of the treatment of tumor cells of MCa mammary carcinoma and TLX5 lymphoma with the ruthenium complex Na[trans-RuCl(4) (DMSO)lm] for several transplant generations were studied on tumor growth and metastases formation. On TLX5 lymphoma cells, treatment was performed in vitro prior to in vivo inoculation of tumor cells in intact or immunesuppressed mice. Either considering tumor take and growth or its capacity to invade the brain of the inoculated hosts, Na[trans-RuCl(4)(DMSO)lm] did not induce any significant modification. Conversely, in mice with MCa mammary carcinoma, the in vivo treatment of tumor cells in immunesuppressed hosts caused a progressive increase of DNA activity and, starting from the 4th transplant generation, a significantly increased susceptibility of lung metastasis formation to a further treatment in intact mice. These data seem to suggest that Na[trans-RuCl(4)(DMSO)Im] does not induce chemical xenogenization of tumor cells nor its repeated treatment induces resistance in tumor cells. Conversely, it appears that Na[trans-RuCl(4)(DMSO)lm] may select a tumor cell population which maintains its capacity to metastasise to the lung but with enhanced sensitivity to the antimetastatic properties of this compound.