Search

The fact that the polymorphic outcome of crystallization is the result of the interplay between the relative thermodynamic stability and nucleation kinetics is well known.

Li-Ce-Ta (LCT) pegmatites containing lithium mineralization in the form of spodumene and lepidolite, as well as fuchsite, from the regions of northern Scandinavia (N Norway, N Finland, N Russia) were studied. Detailed analyses of the chemical compositions of these minerals were carried out, involving scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy with attenuated total reflectance (ATR), and X-ray photoelectron spectroscopy (XPS) studies. Their crystal structures were confirmed with the X-ray diffraction technique. Studies involving microscopy were also carried out, indicating the optical features of these minerals. Based on the analyses carried out in the studied rocks, the characteristics of these minerals were determined, as well as the crystallization conditions. This research indicates that the N Scandinavian area is prospective and may lead to further discoveries of this type of pegmatite in the studied region.

Aberrant signaling of the nuclear facotr (NF-κB) pathway has been identified as a mediator of survival and apoptosis resistance in leukemias and lymphomas. Here, we report that cell death of cutaneous T-cell lymphoma cell lines induced by inhibition of the NF-κB pathway is independent of caspases or classic death receptors. We found that free intracellular iron and reactive oxygen species (ROS) are the main mediators of this cell death. Antioxidants such as N-Acetyl-l-cysteine and glutathione or the iron chelator desferrioxamine effectively block cell death in cutaneous T-cell lymphoma cell lines or primary T cells from Sézary patients. We show that inhibition of constitutively active NF-κB causes down-regulation of ferritin heavy chain (FHC) that leads to an increase of free intracellular iron, which, in turn, induces massive generation of ROS. Furthermore, direct down-regulation of FHC by siRNA caused a ROS-dependent cell death. Finally, high concentrations of ROS induce cell death of malignant T cells. In contrast, T cells isolated from healthy donors do not display down-regulation of FHC and, therefore, do not show an increase in iron and cell death upon NF-κB inhibition. In addition, in a murine T-cell lymphoma model, we show that inhibition of NF-κB and subsequent down-regulation of FHC significantly delays tumor growth in vivo. Thus, our results promote FHC as a potential target for effective therapy in lymphomas with aberrant NF-κB signaling. [Cancer Res 2009;69(6):2365–74]

Supplementary Figure 1 from Inhibition of Constitutively Activated Nuclear Factor-κB Induces Reactive Oxygen Species- and Iron-Dependent Cell Death in Cutaneous T-Cell Lymphoma

Supplementary Figure Legends 1-3 from Inhibition of Constitutively Activated Nuclear Factor-κB Induces Reactive Oxygen Species- and Iron-Dependent Cell Death in Cutaneous T-Cell Lymphoma

Supplementary Figure 3 from Inhibition of Constitutively Activated Nuclear Factor-κB Induces Reactive Oxygen Species- and Iron-Dependent Cell Death in Cutaneous T-Cell Lymphoma

Supplementary Materials and Methods from Inhibition of Constitutively Activated Nuclear Factor-κB Induces Reactive Oxygen Species- and Iron-Dependent Cell Death in Cutaneous T-Cell Lymphoma

Supplementary Figure 2 from Inhibition of Constitutively Activated Nuclear Factor-κB Induces Reactive Oxygen Species- and Iron-Dependent Cell Death in Cutaneous T-Cell Lymphoma

The objective of this study was to determine changes in fuel delivery rate by common rail system injectors during their simulated operation on a test stand. Four Bosch injectors used, among others, in Fiat 1.3 Multijet engines were tested. The injectors were operated on a test rig at room temperature for 500 hours (more than 72 million work cycles). During the test, pressure and injection frequency were changed. Changes in the operating parameters were estimated based on obtained injection characteristics and effective flow area determined thereby. The observed changes in fuel delivery rate were compared with results of the surface analysis of control valves and nozzle needles. Despite the stated lack of wear, significant changes in the dynamics of injector operation were observed, particularly at short injection times. Small pilot injections cannot be corrected by the fuel injection control system because they do not affect the changes in torque; however, they do affect the combustion process. This creates conditions for increased emission of toxic exhaust components.

The article presents Józef Korycki, called Janosik Podlaski, described in the accounts of his three friends. The source material was developed with the biographical method and subjected to critical analysis. The accounts revealed the axiological ambiguity of Korycki’s activities, as well as the differences in opinions about his activities. In the eyes of the communist propaganda, Janosik Podlaski was a common criminal. However, in the memory of friends he remained a good man, loyal to his homeland and devoted to the Podlasie community. In addition to presenting the recollections of Korycki, the article offers a clear interpretation of activities of this outstanding man. Artykuł prezentuje postać Józefa Koryckiego, zwanego Janosikiem Podlaskim, opisaną na podstawie relacji trójki jego przyjaciół. Pozyskany w ten sposób materiał został opracowany w oparciu o metodę biograficzną i poddany krytycznej analizie. Relacje uwidoczniły niejednoznaczność aksjologiczną działalności Koryckiego, a także wynikającą z tego rozbieżność ocen prowadzonych przezeń działań. Ukazały zależność dotyczących jego osoby i czynów sądów wartościujących od perspektywy postrzegania. W ujęciu propagandy komunistycznych władz, Janosik Podlaski przedstawiany był, jako pospolity kryminalista. Natomiast w pamięci przyjaciół pozostał dobrym człowiekiem, wiernym ojczyźnie i oddanym podlaskiej społeczności. Artykuł ma na celu, oprócz prezentacji wspomnień o Koryckim, także przybliżenie rozstrzygnięcia dylematu w historycznej ocenie tej nieprzeciętnej postaci.

Objective The main objective of the present work was to assess the utility of KA-104 as potential therapy for drug-resistant seizures and neuropathic pain, and to characterize its druglike properties in a series of absorption, distribution, metabolism, excretion and toxicity (ADME-Tox) studies. We also aimed to establish its mechanism of action in electrophysiological studies. Methods The activity of KA-104 against drug-resistant seizures was tested in the mouse 6-Hz (44-mA) model, whereas the antinociceptive activity was assessed with the capsaicin- and oxaliplatin-induced pain models in mice. The patch-clamp technique was used to study the influence of KA-104 on fast voltage-gated sodium currents in rat prefrontal cortex pyramidal neurons. The pharmacokinetic profile was determined after intraperitoneal (ip) injection in mice. The in vitro ADME-Tox properties were studied by applying routine testing procedures. Results KA-104 was effective in the 6-Hz (44-mA) model (median effective dose [ED50 ] = 73.2 mg/kg) and revealed high efficacy in capsaicin-induced neurogenic pain as well as in oxaliplatin-induced neuropathic pain in mice. Patch-clamp technique showed that KA-104 reversibly inhibits voltage-gated sodium currents. KA-104 was rapidly absorbed after the ip injection and showed relatively good penetration through the blood-brain barrier. This molecule was also characterized by high passive permeability, moderate influence on CYP2C9, and negligible hepatotoxicity on HepG2 cells. Significance The results reported herein indicate that KA-104 is a new wide-spectrum multitargeted anticonvulsant with favorable in vitro ADME-Tox properties. Importantly, this compound may also prove to become an interesting and hopefully more effective therapeutic option for treatment of neuropathic pain.

(R)-7 [(R)-AS-1] showed broad-spectrum antiseizure activity across in vivo mouse seizure models: maximal electroshock (MES), 6 Hz (32/44 mA), acute pentylenetetrazol (PTZ), and PTZ-kindling. A remarkable separation between antiseizure activity and CNS-related adverse effects was also observed. In vitro studies with primary glia cultures and COS-7 cells expressing the glutamate transporter EAAT2 showed enhancement of glutamate uptake, revealing a stereoselective positive allosteric modulator (PAM) effect, further supported by molecular docking simulations. (R)-7 [(R)-AS-1] was not active in EAAT1 and EAAT3 assays and did not show significant off-target activity, including interactions with targets reported for marketed antiseizure drugs, indicative of a novel and unprecedented mechanism of action. Both in vivo pharmacokinetic and in vitro absorption, distribution, metabolism, excretion, toxicity (ADME-Tox) profiles confirmed the favorable drug-like potential of the compound. Thus, (R)-7 [(R)-AS-1] may be considered as the first-in-class small-molecule PAM of EAAT2 with potential for further preclinical and clinical development in epilepsy and possibly other CNS disorders.

We report herein a series of water-soluble analogues of previously described anticonvulsants and their detailed in vivo and in vitro characterization. The majority of these compounds demonstrated broad-spectrum anticonvulsant properties in animal seizure models, including the maximal electroshock (MES) test, the pentylenetetrazole-induced seizure model (scPTZ), and the psychomotor 6 Hz (32 mA) seizure model in mice. Compound 14 showed the most robust anticonvulsant activity (ED50 MES = 49.6 mg/kg, ED50 6 Hz (32 mA) = 31.3 mg/kg, ED50scPTZ = 67.4 mg/kg). Notably, it was also effective in the 6 Hz (44 mA) model of drug-resistant epilepsy (ED50 = 63.2 mg/kg). Apart from favorable anticonvulsant properties, compound 14 revealed a high efficacy against pain responses in the formalin-induced tonic pain, the capsaicin-induced neurogenic pain, as well as in the oxaliplatin-induced neuropathic pain in mice. Moreover, compound 14 showed distinct anti-inflammatory activity in the model of carrageenan-induced aseptic inflammation. The mechanism of action of compound 14 is likely complex and may result from the inhibition of peripheral and central sodium and calcium currents, as well as the TRPV1 receptor antagonism as observed in the in vitro studies. This lead compound also revealed beneficial in vitro ADME-Tox properties and an in vivo pharmacokinetic profile, making it a potential candidate for future preclinical development. Interestingly, the in vitro studies also showed a favorable induction effect of compound 14 on the viability of neuroblastoma SH-SY5Y cells.

Idiopathic pulmonary fibrosis (IPF) is a progressive and eventually fatal lung disease with a complex etiology. Approved drugs, nintedanib and pirfenidone, modify disease progression, but IPF remains incurable and there is an urgent need for new therapies. We identified chitotriosidase (CHIT1) as new driver of fibrosis in IPF and a novel therapeutic target. We demonstrate that CHIT1 activity and expression are significantly increased in serum (3-fold) and induced sputum (4-fold) from IPF patients. In the lungs CHIT1 is expressed in a distinct subpopulation of profibrotic, disease-specific macrophages, which are only present in patients with ILDs and CHIT1 is one of the defining markers of this fibrosis-associated gene cluster. To define CHIT1 role in fibrosis, we used the therapeutic protocol of the bleomycin-induced pulmonary fibrosis mouse model. We demonstrate that in the context of chitinase induction and the macrophage-specific expression of CHIT1, this model recapitulates lung fibrosis in ILDs. Genetic inactivation of Chit1 attenuated bleomycin-induced fibrosis (decreasing the Ashcroft scoring by 28%) and decreased expression of profibrotic factors in lung tissues. Pharmacological inhibition of chitinases by OATD-01 reduced fibrosis and soluble collagen concentration. OATD-01 exhibited anti-fibrotic activity comparable to pirfenidone resulting in the reduction of the Ashcroft score by 32% and 31%, respectively. These studies provide a preclinical proof-of-concept for the antifibrotic effects of OATD-01 and establish CHIT1 as a potential new therapeutic target for IPF.

Nowadays, high-precision machines require lightweight materials with very high strength. Ion implantation is used to improve the mechanical strength of the material. A further paper presents the influence of manganese and nitrogen ion implantation on changes of microhardness of the surface layer of cobalt alloy. Samples were analyzed with the SEM-EDS Phenom ProX microscope. Microhardness was assessed with the Vickers method, and the loads of 1 gf (0.00981 N) and 5 gf (0.049 N) was applied using a FM-800 from Future-Tech microhardness meter. At a load of 1 gf, the penetration depth of the implanted specimens was reached not exceeding 0.5 um. At this depth, all samples showed an increase in microhardness compared to the unimplanted sample. The highest increase in microhardness was achieved after implantation of Mn ions with dose D=1∙1017 Mn+/cm2 and energy E=175 keV. The increased load on the indenter to 5 gf reduced the microhardness differences between implanted and unimplanted samples.

This paper discusses the failure of the over-chamber reinforced concrete ceiling of a cylindrical silo for storing extracted rapeseed meal. The failure resulted from the caving in of an arch formed in the chamber and the sliding down of the material column. Some factors contributing to the caking and arching of the cohesive materials stored in silos are identified. An analysis of the extraordinary loads during the autogenous or induced clearance of arches is made. Such loads are not taken into account by design standards. Attention was paid to the necessity of figuring these loads in the design (an own proposition was put forward); also, ways of preventing such impact or its limitation were pointed out. The direct cause and the indirect causes of the failure are determined. Design and utilization errors which contributed to the formation of the arch, the failure of the ceiling of silo and the compounding of the failure consequences are identified.

From the wide range of engineering materials traditional Stellite 6 (cobalt alloy) exhibits excellent resistance to cavitation erosion (CE). Nonetheless, the influence of ion implantation of cobalt alloys on the CE behaviour has not been completely clarified by the literature. Thus, this work investigates the effect of nitrogen ion implantation (NII) of HIPed Stellite 6 on the improvement of resistance to CE. Finally, the cobalt-rich matrix phase transformations due to both NII and cavitation load were studied. The CE resistance of stellites ion-implanted by 120 keV N+ ions two fluences: 5 × 1016 cm−2 and 1 × 1017 cm−2 were comparatively analysed with the unimplanted stellite and AISI 304 stainless steel. CE tests were conducted according to ASTM G32 with stationary specimen method. Erosion rate curves and mean depth of erosion confirm that the nitrogen-implanted HIPed Stellite 6 two times exceeds the resistance to CE than unimplanted stellite, and has almost ten times higher CE reference than stainless steel. The X-ray diffraction (XRD) confirms that NII of HIPed Stellite 6 favours transformation of the ɛ(hcp) to γ(fcc) structure. Unimplanted stellite ɛ-rich matrix is less prone to plastic deformation than γ and consequently, increase of γ phase effectively holds carbides in cobalt matrix and prevents Cr7C3 debonding. This phenomenon elongates three times the CE incubation stage, slows erosion rate and mitigates the material loss. Metastable γ structure formed by ion implantation consumes the cavitation load for work-hardening and γ → ɛ martensitic transformation. In further CE stages, phases transform as for unimplanted alloy namely, the cavitation-inducted recovery process, removal of strain, dislocations resulting in increase of γ phase. The CE mechanism was investigated using a surface profilometer, atomic force microscopy, SEM-EDS and XRD. HIPed Stellite 6 wear behaviour relies on the plastic deformation of cobalt matrix, starting at Cr7C3/matrix interfaces. Once the Cr7C3 particles lose from the matrix restrain, they debond from matrix and are removed from the material. Carbides detachment creates cavitation pits which initiate cracks propagation through cobalt matrix, that leads to loss of matrix phase and as a result the CE proceeds with a detachment of massive chunk of materials.

In the current studies we carried out an optimized multistep asymmetric synthesis of R-enantiomers (eutomers) for a previously identified series of racemic hybrid anticonvulsants. The spatial structure of selected enantiomers was solved by the use of crystallographic methods. The compound (R)-16 was identified as a lead, which revealed broad-spectrum protective activity in a range of epilepsy models with the following ED50 values: the maximal electroshock (MES) test (36.0 mg/kg), the 6 Hz (32 mA) seizure model (39.2 mg/kg), and the pentylenetetrazole-induced seizure model (scPTZ) (54.8 mg/kg). Furthermore, (R)-16 displayed a low potency for the induction of motor impairment in the rotarod test (TD50 = 468.5 mg/kg), resulting in potentially very beneficial therapeutic window. Finally, (R)-16 showed satisfying ADME-Tox properties in the in vitro assays. Therefore, the data obtained in the current studies justify the further preclinical development of (R)-16 as candidate for potentially broad-spectrum and safe anticonvulsant.

Epilepsy belongs to the most common and debilitating neurological disorders with multifactorial pathophysiology and a high level of drug resistance. Therefore, with the aim of searching for new, more effective, and/or safer therapeutics, we discovered a focused series of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant properties. We applied an optimized coupling reaction yielding several hybrid compounds that showed broad-spectrum activity in widely accepted animal seizure models, namely, the maximal electroshock (MES) test and the psychomotor 6 Hz (32 mA) seizure model in mice. The most potent anticonvulsant activity and favorable safety profile was demonstrated for compound 30 (median effective dose (ED50) MES = 45.6 mg/kg, ED50 6 Hz (32 mA) = 39.5 mg/kg, median toxic dose (TD50) (rotarod test) = 162.4 mg/kg). Anticonvulsant drugs often show activity in pain models, and compound 30 was also proven effective in the formalin test of tonic pain, the capsaicin-induced pain model, and the oxaliplatin (OXPT)-induced neuropathic pain model in mice. Our studies showed that the most plausible mechanism of action of 30 involves inhibition of calcium currents mediated by Cav1.2 (L-type) channels. Importantly, 30 revealed high metabolic stability on human liver microsomes, negligible hepatotoxicity, and relatively weak inhibition of CYP3A4, CYP2D6, and CYP2C9 isoforms of cytochrome P450, compared to reference compounds. The promising in vivo activity profile and drug-like properties of compound 30 make it an interesting candidate for further preclinical development.

We developed a focused set of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant and antinociceptive properties. These hybrid compounds demonstrated broad-spectrum protective activity in a range of mouse models, such as the maximal electroshock (MES) test, the pentylenetetrazole-induced seizures (

A titanium sample was irradiated with Xe 168 MeV energy at fluences of 1 × 1014, 2.2 × 1014, and 5 × 1014 ions · m−2. Changes induced by the ions with irradiation were analysed with an atomic force microscope, scanning electron microscope, and X-ray diffractometer. The irradiation at a fluence of 1 × 1014 ions · cm−2 leads to formation of hillocks with a density of 9 × 106 hillocks · cm−2. An increase in the fluence value results in disappearance of the hillocks and formation of void–dislocation lines. The changes in the surface topography are accompanied by a change in the relative content of the hcp (α) and fcc phases. The substantial changes in the crystalline structure (increased content of the fcc phase, reduction of lattice constants, changes in stresses) resulted from irradiation at a fluence of 1 × 1014 ions · cm−2. Irradiation of massive titanium samples with xenon ions at a fluence of 168 MeV 1 × 1014 ions · cm−2 at room temperature leads to a transition of ∼10% of the hexagonally closed-packed phase – hcp (α) into a face centred cubic structure (the fcc phase). Higher Xe ion fluences contribute to further reduction of lattice constants and crystallite sizes as well as reduction of the phase fcc content and lower values of stresses. It has been found for the first time that irradiation at higher fluences leads to partial recovery of the hcp (α) phase. Irradiation changes the texture of∼50% of the fcc phase crystallites.

The crisis related to the COVID 19 pandemic caused an increase in nickel prices on the global markets. From this perspective, it seems promising to search for the possibilities of effective recycling of nickel-based alloys as biomaterials. The topic of the recasting of Ni-Cr dental alloys is currently being broadly described in the literature. Nonetheless, there are still no conclusive results on the impact of recasting on the quality of the cast dentures. Considering the aforementioned, for research, the effect of recasting on the wear resistance and microstructure of NiCrMo dental alloy was investigated. The Heraenium NA alloy was used for testing. Abrasion resistance was tested by the ball on disc method. Microstructure and wear trace were observed using an optical microscope and a scanning electron microscope. The tests showed a higher wear resistance of the re-casted material. The average coefficient of friction for the initially cast alloys was 0.664, while for the remelted samples the mean value was 0.441. The tested samples are characterised by an abrasive-adhesive wear mechanism. Piling up of the wear tracks edges was observed – the highest for H100. For the H100 samples, a slightly lower average hardness value (HV10) was observed – 226 compared to 233 (HV10) for the samples made from the re-casted alloy (H0). The presence of a dendritic structure of alloys was demonstrated. Blocky eutectic precipitations are visible against the matrix. The observed growth of interdendritic precipitations constitute a natural barrier for the counterpart material and increases its tribological properties. Obtained results suggest that alloy recasting does not constitute a limitation to its use.

The influence of nitrogen ion implantation on the tribological properties of Stellite 6 cobalt alloy was investigated. The tribological tests were conducted using a pin / ball on disc in the atmosphere of engine fuels. In the study, cobalt alloy was implanted with 60 keV nitrogen ions at the fluence of 1∙1016 and 5∙1016 N+/cm2. The wear trace was measured using the Form Talysurf Intra Taylor Hobson profilometer. The results demonstrate that nitrogen ion implantation affects the friction coefficient and wear. The effect of nitrogen ion implantation depends on the environment in which the tribological test is carried out, the sample temperature and the presence of friction products in the friction node.

Xanthohumol, a major prenylated chalcone found in hop resin, has recently attracted scientific interest due to its health-promoting properties. In the present work, we investigated the mechanism of xanthohumol cyclization to isoxanthohumol in an aqueous solution with a high pH by means of UV–Vis spectroscopy and liquid chromatography. The results were modeled by DFT methods with the SMD solvation model. The results of theoretical calculations were consistent with experimental data. The proposed mechanism comprises two stages, where the first step involves cyclization of xanthohumol ions and the second step involves the addition of H + ion from a water molecule to an isoxanthohumol ion. The second step is responsible for the stabilization of isoxanthohumol. Based on these results some practical information can be drawn, which may be important from the point of view of the problem xanthohumol stability in commercial dietary supplements.

This paper presents examples of the application of the TDR (Time-Domain Reflectometry) sensor in terramechanical research. Examples include the determination of soil moisture content during off-road vehicle mobility tests, the determination of snow density before and after the wheeling of a snow grooming machine and an airplane, as well as the monitoring of turf moisture on a grassy airfield for the analysis and prediction of safe and efficient flight operations (takeoff and landing). A handheld TDR meter was used in these experiments. Soil moisture data were correlated with the vehicle mobility index and a simple model for this correlation was derived. Using grassy airfield research, soil moisture data were related to meteorological impacts (precipitation, sunlight, etc.). Generally, it was concluded that the TDR meter, in its handheld version, was a useful tool in the performed research, but a field sensor that operates autonomically would be an optimal solution for the subject applications.

Stainless steel grade AISI 304 is one of the most widespread modern structural material, alas its sliding wear and cavitation wear resistance are limited. Thus, AlTiN and TiAlN coatings can be deposited for increasing the resistance to wear of stainless steel components. The aim of the work was to investigate the cavitation erosion and sliding wear mechanisms of magnetron sputtered AlTiN and TiAlN coatings deposited on SS304 stainless steel. Films surface morphology and structure were examined using a profilometer, light optical microscope (LOM) and scanning electron microscope (SEM). The mechanical properties (hardness, elastic modulus) were tested by nanoindentation tester. The adhesion of deposited coatings was determined by means of the scratch test and Rockwell test. Cavitation erosion tests were performed according to ASTM G32 (vibratory apparatus) with stationary specimen procedure. Sliding wear tests were conducted using a nano-tribo testes i.e. ball-on-disc apparatus. Wear mechanisms are strongly contingent upon the structure and morphology of the tested materials. In relation to stainless steel substrate, the PVD films present a superior resistance to sliding wear and cavitation erosion. Higher resistance was noticed for AlTiN than for TiAlN film, mainly due to its superior hardness and elastic modulus. Cavitation erosion mechanism of both, AlTiN and AlTiN coatings is prone to embrittlement, imputable to fatigue processes that result in coating rupture and spallation that consist in coating fragmentation, formation of pits and finally detachment from the substrate. Additionally, films nanoindentation results measured before and after cavitation testing indicate changes in coatings structure, that acknowledged wear mechanism that starts with coating internal delamination in flake spallation mode. In contrary to PVD coatings, steel substrate is characterized by developed cavitation erosion wear with roughened surface and plastically deformed, semi-brittle, eroded surface. Sliding wear of thin films is based on micro-ploughing mechanism. For stainless steel adhesive sliding wear mode and plastic deformation with smearing, material transfer and grooving were observed. It was confirmed that various fluid machinery components made from austenitic stainless steel that undergo cavitation erosion, can be prevented by deposition of AlTiN and TiAlN films.