Deformation information system for facilitating studies of mining-ground deformations, development, and applications

The paper presents the concept of the deformation information system (DIS) to support and facilitate studies of mining-ground deformations. The proposed modular structure of the system includes data collection and data visualisation components, as well as spatial data mining, modelling and classification modules. In addition, the system integrates interactive three-dimensional models of the mines and local geology. The system is used to calculate various parameters characterising ground deformation in space and time, i.e. vertical and horizontal displacement fields, deformation parameters (tilt, curvature, and horizontal strain) and input spatial variables for spatial data classifications. The core of the system in the form of an integrated spatial and attributive database has been described. The development stages and the functionality of the particular components have been presented and example analyses utilising the spatial data mining and modelling functions have been shown. These include, among other things, continuous vertical and horizontal displacement field interpolations, calculation of parameters characterising mining-ground deformations, mining-ground category classifications, data extraction procedures and data preparation preprocessing procedures for analyses in external applications. The DIS has been developed for the Walbrzych coal mines area in SW Poland where long-time mining activity ended at the end of the 20th century and surface monitoring is necessary to study the present-day condition of the former mining grounds

Synthesis and in vitro antiproliferative activity of novel (4-chloro- and 4-acyloxy-2-butynyl)thioquinolines

The series of new acetylenic thioquinolines containing propargyl, 4-chloro-2-butynyl, and 4-acyloxy-2-butynyl groups have been prepared and tested for antiproliferative activity in vitro against human [SW707 (colorectal adenocarcinoma), CCRF/CEM (leukemia), T47D (breast cancer)] and murine [P388 (leukemia), B16 (melanoma)] cancer lines. Most of the obtained compounds exhibited antiproliferative activity, especially compounds 8, 12, and 21 showed the ID50 values ranging from 0.4 to 3.8 μg/ml comparable to that of cisplatin used as reference compounds

p53 Activation following Rift Valley Fever Virus Infection Contributes to Cell Death and Viral Production

Rift Valley fever virus (RVFV) is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production

p53 Regulates Cell Cycle and MicroRNAs to Promote Differentiation of Human Embryonic Stem Cells

Multiple studies show that tumor suppressor p53 is a barrier to dedifferentiation; whether this is strictly due to repression of proliferation remains a subject of debate. Here, we show that p53 plays an active role in promoting differentiation of human embryonic stem cells (hESCs) and opposing self-renewal by regulation of specific target genes and microRNAs. In contrast to mouse embryonic stem cells, p53 in hESCs is maintained at low levels in the nucleus, albeit in a deacetylated, inactive state. In response to retinoic acid, CBP/p300 acetylates p53 at lysine 373, which leads to dissociation from E3-ubiquitin ligases HDM2 and TRIM24. Stabilized p53 binds CDKN1A to establish a G1 phase of cell cycle without activation of cell death pathways. In parallel, p53 activates expression of miR-34a and miR-145, which in turn repress stem cell factors OCT4, KLF4, LIN28A, and SOX2 and prevent backsliding to pluripotency. Induction of p53 levels is a key step: RNA-interference-mediated knockdown of p53 delays differentiation, whereas depletion of negative regulators of p53 or ectopic expression of p53 yields spontaneous differentiation of hESCs, independently of retinoic acid. Ectopic expression of p53R175H, a mutated form of p53 that does not bind DNA or regulate transcription, failed to induce differentiation. These studies underscore the importance of a p53-regulated network in determining the human stem cell state

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs) and sickness behavior

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Keratins extracted from Merino wool and Brown Alpaca fibres as potential fillers for PLLA-based biocomposites

This paper reports on the promising perspectives of using keratins extracted by sulphitolysis reaction from Merino wool (KM) and Brown Alpaca fibres (KA) in poly (l-lactide) (PLLA)-based biomaterials. Both types of keratin were dispersed in chloroform (CHCl3) and tetrahydrofuran (THF), and optimisation of dispersion methods and parameters using the two selected solvents was considered. The extraction yield, as well as supermolecular structures, morphology and thermal behaviour of the two proteins before and after the regeneration in CHCl3 was investigated. The results indicated that the supermolecular structures and thermal behaviour of the two proteins were affected by the interaction with CHCl3, producing decrease of the amount of α-helix structures in KM and an increase for KA, a slight decrease of β-sheet structures and a reduced thermal stability of α-crystallites for both keratins. Biocomposite films based on PLLA polymer matrix and two different contents of Merino wool and Brown Alpaca keratins (1 % and 5 % wt) were successfully developed by solvent casting in chloroform and the resulting morphologies after incorporation of different keratins (as a function of content and source) give evidence of different surface topographies, with a random distribution of keratin in flask-like structure. PLLA/5KA and PLLA/5KM samples with 1 % and 5 % wt of keratins show a specific pore-like surface microstructure, induced by solvent evaporation.Peer Reviewe