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While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers. These filaments lead to RAI2-mediated CtBP nuclear foci and relieve its corepressor function in RAI2-expressing cancer cells. The impact of RAI2-mediated CtBP loss-of-function is illustrated by the analysis of a diverse cohort of prostate cancer patients, which reveals a substantial decrease in RAI2 in advanced treatment-resistant cancer subtypes. As RAI2-like SLiM motifs are found in a wide range of organisms, including pathogenic viruses, our findings serve as a paradigm for diverse functional effects through multivalent interaction-mediated polymerization by disordered proteins in healthy and diseased conditions. CtBP is a transcriptional master co-repressor with oncogenic activity. Here, the authors use structural and biophysical methods to show that CtBP interacts with RAI2 through SLiMs that induce CtBP polymerization and inactivation. [ABSTRACT FROM AUTHOR]

Rationale: In bipolar disorder (BD), immunological factors play a role in the pathogenesis and treatment of the illness. Studies showed the potential link between Abelson Helper Integration Site 1 (AHI1) protein, behavioural changes and innate immunity regulation. An immunomodulatory effect was suggested for lithium, a mood stabilizer used in BD treatment. Objectives: We hypothesized that AHI1 may be an important mediator of lithium treatment response. Our study aimed to investigate whether the AHI1 haplotypes and expression associates with lithium treatment response in BD patients. We also examined whether AHI1 expression and lithium treatment correlate with innate inflammatory response genes. Results: We genotyped seven AHI1 single nucleotide polymorphisms in 97 euthymic BD patients and found that TG haplotype (rs7739635, rs9494332) was significantly associated with lithium response. We also showed significantly increased AHI1 expression in the blood of lithium responders compared to non-responders and BD patients compared to healthy controls (HC). We analyzed the expression of genes involved in the innate immune response and inflammatory response regulation (TLR4, CASP4, CASP5, NLRP3, IL1A, IL1B, IL6, IL10, IL18) in 21 lithium-treated BD patients, 20 BD patients treated with other mood stabilizer and 19 HC. We found significantly altered expression between BD patients and HC, but not between BD patients treated with different mood stabilizers. Conclusions: Our study suggests the involvement of AHI1 in the lithium mode of action. Moreover, mood-stabilizing treatment associated with the innate immunity-related gene expression in BD patients and only the lithium-treated BD patients showed significantly elevated expression of anti-inflammatory IL10, suggesting lithium's immunomodulatory potential. [ABSTRACT FROM AUTHOR]

The FTO gene rs9936909 polymorphism is one of the well-documented single nucleotide polymorphisms in the context of increased risk of obesity, including in children. Few studies have tested the association of the FTO gene with cognitive functions. Deficits of "cool" executive functions (EFs) are considered a potential risk factor for excessive weight. The aims of our study were to investigate whether cool EFs are associated with the Body Mass Index, the Fat Mass Index and the risk of excess body mass and overfatness in neurotypically school-aged children, and whether the FTO gene polymorphism is involved in development of this possible association. The sample consisted of 553 children aged 6–12 years old. A body composition analysis, a neuropsychological assessment of EFs, and FTO polymorphism genotyping were performed in the children studied. The study found a significant association of an interference effect in theStroop Color-Word Interference Task and the risk of excessive body fatness, but not excessive body mass. There were no explicit associations between the FTO genotype and EFs deficits. Environmental factors, and particularly low maternal education, appeared to be the strongest contributors to the increased risk of obesity. [ABSTRACT FROM AUTHOR]

Despite the significant prevalence of Major Depressive Disorder in the pediatric population, the pathophysiology of this condition remains unclear, and the treatment outcomes poor. Investigating tools that might aid in diagnosing and treating early-onset depression seems essential in improving the prognosis of the future disease course. Recent studies have focused on searching for biomarkers that constitute biochemical indicators of MDD susceptibility, diagnosis, or treatment outcome. In comparison to increasing evidence of possible biomarkers in adult depression, the studies investigating this subject in the youth population are lacking. This narrative review aims to summarize research on molecular and biochemical biomarkers in child and adolescent depression in order to advocate future directions in the research on this subject. More studies on depression involving the youth population seem vital to comprehend the natural course of the disease and identify features that may underlie commonly observed differences in treatment outcomes between adults and children. [ABSTRACT FROM AUTHOR]

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ruxolitinib (RUX), an oral JAK1 and JAK2 inhibitor, has recently been approved for patients with SR-aGVHD. The aim of this study was to evaluate RUX efficacy and toxicity in a real-world setting. Eighteen patients received RUX at 5 mg or 10 mg twice a day after a median 3 lines of prior unsuccessful immunosuppressive therapy. Median time on RUX therapy was 28 days (range 7–129). Five patients (28%) responded to RUX, including 4 complete responses and 1 partial response. Response to RUX was irrespective of aGVHD grade and the number of involved organs. One-year overall survival (OS) was 60% for RUX-responders versus 31% for non-responders (p = ns). Treatment duration greater than 29.5 days was found to have a positive impact on OS (p < 0.007). Major adverse events during RUX treatment were grade 3–4 thrombocytopenia (61% of patients) and cytomegalovirus reactivation (50%). After median follow-up of 55 days (range 29–706), 14 patients (78%) died, mainly due to further progression of GVHD. RUX may represent a valuable therapeutic option for some patients with advanced SR-aGVHD, but more studies are warranted. [ABSTRACT FROM AUTHOR]

Hydrogel wound dressings are highly effective in the therapy of wounds. Yet, most of them do not contain any active ingredient that could accelerate healing. The aim of this study was to prepare hydrophilic active dressings loaded with an anti-inflammatory compound - trans-resveratrol (RSV) of hydrophobic properties. A special attention was paid to select such a technological strategy that could both reduce the risk of irritation at the application site and ensure the homogeneity of the final hydrogel. RSV dissolved in Labrasol was combined with an aqueous sol of poly(vinyl) alcohol (PVA), containing propylene glycol (PG) as a plasticizer. This sol was transformed into a gel under six consecutive cycles of freezing (-80 °C) and thawing (RT). White, uniform and elastic membranes were successfully produced. Their critical features, namely microstructure, mechanical properties, water uptake and RSV release were studied using SEM, DSC, MRI, texture analyser and Franz-diffusion cells. The cryogels made of 8 % of PVA showed optimal tensile strength (0.22 MPa) and elasticity (0.082 MPa). The application of MRI enabled to elucidate mass transport related phenomena in this complex system at the molecular (detection of PG, confinement effects related to pore size) as well as at the macro level (swelling). The controlled release of RSV from membranes was observed for 48 h with mean dissolution time of 18 h and dissolution efficiency of 35 %. All in all, these cryogels could be considered as a promising new active wound dressings. [ABSTRACT FROM AUTHOR]

To maintain its functional abilities, the mature brain obtains energy from glucose produced in carbohydrate metabolism. When carbohydrates are eliminated from the diet, the energy comes from the oxidation of fatty acids. In this metabolic state called ketosis, ketone bodies are formed: β-hydroxybutyric acid (bHb), acetone, and acetoacetate as alternative source of energy passing through the blood–brain barrier easily. The ketosis state can be achieved through various strategies like caloric restriction, supplementation with medium-chain triglycerides, intense physical training, or ketogenic diet (KD). Using KD, drug-resistant epilepsy has been successfully treated in children and adults. It can also exert neuroprotective influences in cases of brain damage, glioblastoma multiforme, and Alzheimer's or Parkinson's diseases. Although many possible mechanisms of KD activity have been proposed, newer hypotheses appear with the research progress, mostly characterizing the brain under pathological but not normal conditions. Since different pathological conditions may affect the mechanism of KD action differently, additional research on the normal brain appears reasonable. For this purpose, young adult rats were treated with 4-month-lasting KD. Then, MRI structural measurements, spectroscopy, and tractography were performed. The procedures revealed significant increases in the concentration of glutamine, glutamate, glutathione and NAA, accompanied by changes in the pattern of neuronal connections of the striatum and hippocampal formation. This implies a possible involvement of these structures in the functional changes occurring in the brain after KD application. Thus, the investigations on the normal brain add important details concerning mechanisms underlying KD effects without their possible modification by a pathological status. [ABSTRACT FROM AUTHOR]

This article addresses the impact of the European Union Emissions Trading System (EU ETS) on Poland’s conventional energy sector in 2008-2020 and further till 2050. Poland is a country with over 80% dependence on coal in the power sector being under political pressure of the European Union’s (EU) ambitious climate policy. The impact of the increase of the European Emission Allowance (EUA) price on fossil fuel power sector has been modelled for different scenarios. The innovation of this article consists in proposing a methodology of estimation actual costs and benefits of power stations in a country with a heavily coal-dependent power sector in the process of transition to a low-carbon economy. Strong political and economic interdependence of coal and power sector has been demonstrated as well as the impact caused by the EU ETS participation in different technology groups of power plants. It has been shown that gas-fuelled combined heat and power units are less vulnerable to the EU ETS-related costs, whereas the hard coal-fired plants may lose their profitability soon after 2020. Lignite power plants, despite their high emissivity, may longer remain in operation owing to low operational costs. Additionally, the results of long-term, up to 2050, modelling of Poland’s energy sector supported an unavoidable need of deep decarbonisation of the power sector to meet the post-Paris climate objectives. It has been concluded that investing in coal-based power capacity may lead to a carbon lock-in of the power sector. Finally, the overall costs of such a transformation have been discussed and confronted with the financial support offered by the EU. The whole consideration has been made in a wide context of changes ongoing globally in energy markets and compared with some other countries seeking transformation paths from coal. Poland’s case can serve as a lesson for all countries trying to reduce coal dependence in power generation. Reforms in the energy sector shall from the very beginning be an essential part of a sustainable transition of the whole nation’s economy. They must scale the power capacity to the future demand avoiding stranded costs. The reforms must be wide-ranging, based on a wide political consensus and not biased against the coal sector. Future energy mix and corresponding technologies shall be carefully designed, matched and should remain stable in the long-term perspective. Coal-based power capacity being near the end of its lifetime provides an economically viable option to commence a fuel switch and the following technology replacement. Real benefits and costs of the energy transition shall be fairly allocated to all stakeholders and communicated to the society. The social costs and implications in coal-dependent regions may be high, especially in the short-term perspective, but then the transformation will bring profits to the whole society. [ABSTRACT FROM AUTHOR]

The gray short-tailed opossum (Monodelphis domestica) is a small marsupial gaining recognition as a laboratory animal in biomedical research. Despite numerous studies on opossum neuroanatomy, a consistent and comprehensive neuroanatomical reference for this species is still missing. Here we present the first three-dimensional, multimodal atlas of the Monodelphis opossum brain. It is based on four complementary imaging modalities: high resolution ex vivo magnetic resonance images, micro-computed tomography scans of the cranium, images of the face of the cutting block, and series of sections stained with the Nissl method and for myelinated fibers. Individual imaging modalities were reconstructed into a three-dimensional form and then registered to the MR image by means of affine and deformable registration routines. Based on a superimposition of the 3D images, 113 anatomical structures were demarcated and the volumes of individual regions were measured. The stereotaxic coordinate system was defined using a set of cranial landmarks: interaural line, bregma, and lambda, which allows for easy expression of any location within the brain with respect to the skull. The atlas is released under the Creative Commons license and available through various digital atlasing web services. [ABSTRACT FROM AUTHOR]

In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features ( i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas- e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products. [ABSTRACT FROM AUTHOR]

Population studies indicate a strong relationship between birth weight (BW) and body size in later life. However, BW as a variable was never accounted for in studies on the relationship between attention-deficit/hyperactivity disorder (ADHD) and overweight. This study aims to assess the relationship between ADHD and overweight with control of birth weight and other confounding factors. Prevalence of overweight was compared in clinical sample of 219 boys with ADHD and 396 boys without ADHD, aged 6-18 years. The following factors were controlled: BW, parents income and education level, place of residence, ADHD type, selected comorbid disorders and stimulant treatment. Overweight and obesity were diagnosed according to the criteria proposed by the International Obesity Task Force. Logistic regression analysis was used to estimate the association between ADHD and the prevalence of overweight and obesity. Boys with ADHD differed significantly from the control group in distribution of low BW (8.2 vs. 3.0 %, χ = 8.23, p = 0.02). Low BW was associated with a lower prevalence of overweight than normal and high BW (0 vs. 12.14 %, χ = 4.12, p = 0.04). Overweight was observed significantly more often in boys with ADHD (17.3 vs. 8.3 %, χ = 11.23, p < 0.001) even after adjustment for BW and other variables (OR = 2.44, 95 % CI 1.38-4.29, p = 0.002) and after controlling for ADHD type, stimulant treatment and selected comorbid disorders. Independently to applied analysis, obesity was not associated with ADHD. Lower birth weight is over twice more often observed in boys with ADHD than in control group. Although this phenomenon may reduce the rate of overweight in the studied group, ADHD remains strongly associated with increased prevalence of overweight. [ABSTRACT FROM AUTHOR]

Purpose: So far, the hydrated part of the HPMC matrix has commonly been denoted as a 'gel' or 'pseudogel' layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena. Methods: Multiparametric, spatially and temporally resolved T MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T signals. Results: Two components in the T decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external 'gel-like' layer. Conclusions: We have introduced a new paradigm in the characterization of hydrating matrices using H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods. [ABSTRACT FROM AUTHOR]

This paper deals with power-aware scheduling of preemptable jobs on identical parallel processors to minimize schedule length when jobs are described by continuous, strictly concave functions relating their processing speed at time t to the amount of power allotted at the moment. Power is a continuous, doubly constrained resource, i.e. both: its availability at time t and consumption over scheduling horizon are constrained. Precedence constraints among jobs are represented by a task-on-arc graph. A methodology based on properties of optimal schedules is presented for solving the problem optimally for a given ordering of nodes in the graph. Heuristics for finding an ordering which leads to possibly short schedules are proposed and examined experimentally. [ABSTRACT FROM AUTHOR]

The ability of gadolinium zirconate pyrochlore for actinides incorporation in its lattice makes this material a possible matrix for the immobilization of nuclear wastes. The aim of the presented work was to develop a novel method of gadolinium zirconate synthesis by using a reactive sintering procedure under high pressure based on commercial ZrO and GdO nanopowders. Samples were analyzed using X-ray diffraction and SEM to check their phase composition and microstructure. The obtained sintered pellets demonstrated peaks characteristic for pyrochlore structure for a wide range of preparation temperatures and high density (99.5 % of the theoretical value). It was found that the resulting materials exhibited a homogeneous microstructure and the average grain size dependent on sintering temperature. [ABSTRACT FROM AUTHOR]

Recently, the advance reservation functionality gained high importance in grids due to increasing popularity of modern applications that require interactive tasks, co-allocation of multiple resources, and performance guarantees. However, simultaneous scheduling, both advance reservations and batch tasks affects the performance. Advance reservations significantly deteriorate flow time of batch tasks and the overall resource utilization, especially in hierarchical scheduling structures. This is a consequence of unknown batch task processing times and the lack of possibility of altering allocations of advance reservations. To address these issues we present a common model for scheduling both computational batch tasks and tasks with advance reservation requests. We propose simple on-line scheduling policies and generic advices that reduce negative impact of advance reservations on a schedule quality. We also propose novel data structures and algorithms for efficient scheduling of advance reservations. A comprehensive experimental analysis is presented to show the influence of advance reservations on resource utilization, mean flow time, and mean tardiness-the criteria significant for administrators, users submitting batch tasks, and users requesting advance reservations, respectively. All experiments were performed with a well-known real workload using the GSSIM simulator. [ABSTRACT FROM AUTHOR]

Purpose: To resolve contradictions found in morphology of hydrating hydroxypropylmethyl cellulose (HPMC) matrix as studied using Magnetic Resonance Imaging (MRI) techniques. Until now, two approaches were used in the literature: either two or three regions that differ in physicochemical properties were identified. Methods: Multiparametric, spatially and temporally resolved T MR relaxometry in situ was applied to study the hydration progress in HPMC matrix tablets using a 11.7 T MRI system. Two spin-echo based pulse sequences-one of them designed to specifically study short T signals-were used. Results: Two components in the T decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T values, were obtained. Based on the data, five different regions and their temporal evolution were identified: dry glassy, hydrated solid like, two interface layers and gel layer. The regions were found to be separated by four evolving fronts identified as penetration, full hydration, total gelification and apparent erosion. Conclusions: The MRI results showed morphological details of the hydrating HPMC matrices matching compound theoretical models. The proposed method will allow for adequate evaluation of controlled release polymeric matrix systems loaded with drug substances of different solubility. [ABSTRACT FROM AUTHOR]

Introduction: Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods: Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results: Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion: Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion. [ABSTRACT FROM AUTHOR]

problem of allocating resources of a grid to workflow applications is considered. The problem consists, generally, in allocating distributed grid resources to tasks of a workflow in such a way that the resource demands of each task are satisfied. Grid resources are divided into computational resources and network resources. Computational tasks and transmission tasks of a workflow are distinguished. We present a model of the problem, and an algorithm for finding feasible resource allocations. A numerical example is included, showing the importance of the resource allocation phase on a grid. Some conclusions and directions for future research are given. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to present a methodology for the processing of Magnetic Resonance Imaging (MRI) data for the quantification of the dosage form matrix evolution during drug dissolution. The results of the study were verified by comparison with other approaches presented in literature. Methods: A commercially available, HPMC-based quetiapine fumarate tablet was studied with a 4.7T MR system. Imaging was performed inside an MRI probe-head coupled with a flow-through cell for 12 h in circulating water. The images were segmented into three regions using threshold-based segmentation algorithms due to trimodal structure of the image intensity histograms. Results: Temporal evolution of dry glassy, swollen glassy and gel regions was monitored. The characteristic features were observed: initial high expansion rate of the swollen glassy and gel layers due to initial water uptake, dry glassy core disappearance and maximum area of swollen glassy region at 4 h, and subsequent gel layer thickness increase at the expense of swollen glassy layer. Conclusions: The temporal evolution of an HPMC-based tablet by means of noninvasive MRI integrated with USP Apparatus 4 was found to be consistent with both the theoretical model based on polymer disentanglement concentration and experimental VIS/FTIR studies. [ABSTRACT FROM AUTHOR]

Lipopolysaccharides also called endotoxins are an integral component of the outer membrane of Gram-negative bacteria. When released from the bacterial surface, they interact with a host immune system, triggering excessive inflammatory response. Lipid A is the biologically most active part of endotoxin, and its activity is modulated by the quantity, quality and arrangement of its fatty acids. Desulfovibrio desulfuricans is sulfate-reducing, Gram-negative bacterium that is supposed to be opportunistic pathogens of humans and animals. In the present study, chemical composition of lipid A from various strains of D. desulfuricans was analyzed by gas chromatography/mass spectrometry. It was found that the fatty acid component of the lipid A contains dodecanoic, tetradecanoic, 3-hydroxytetradecanoic and hexadecanoic acids, and its carbohydrate core is composed of glucosamine. The analysis of 3-acyloxyacyl residue of the lipid A revealed the presence of amide-bound 3-(dodecanoyloxy)tetradecanoic and 3-(hexadecanoyloxy)tetradecanoic acids and ester-bound 3-(tetradecanoyloxy)tetradecanoic acid. It was concluded that both fatty acid and 3-acyloxyacyl residue profiles of the lipid A from the studied bacteria were similar to those of E. coli and S.enterica. [ABSTRACT FROM AUTHOR]

Quantification of p65, p50 and IκBα mRNAs was performed by real time QRT-PCR in Caco-2 cells treated with 10, 50, and 100 μg/mL of Desulfovibrio desulfuricans LPS for 1, 6, 12, and 24 h. A strong increase in expression of p65 and IλBα genes was induced by 10 and 100 μg/mL of LPS at 1 h; after 6 h higher transcript amounts of both genes were observed at 100 μg/mL LPS. The p65 expression level was significantly increased by 50 and 100 μg/mL at 12 h and lowered by all LPS doses at 24 h. No significant differences between IκBα mRNA quantity in cells exposed to LPS at 12 and 24 h were observed. No changes in expression of p50 mRNA were induced by LPS. The expression of p65 gene positively correlated with IκBα gene expression. D. desulfuricans LPS is capable of modulating transcriptional activity of p65 and IκBα genes in intestinal epithelial cells. [ABSTRACT FROM AUTHOR]

We consider the problem of scheduling preemptable, dependent tasks on parallel, identical machines to minimize the makespan. The computational complexity of this problem remains open if the number of machines is fixed and larger than 2. The aim of this paper is to compare two heuristic algorithms on a basis of a computational experiment. The solutions generated by the heuristics are compared with optimal solutions obtained by a branch-and-bound algorithm. Computational results show that the heuristic based on node ordering finds optimal schedules for 99.9% of instances with the maximum relative deviation from optimum of 4.8%. [ABSTRACT FROM AUTHOR]

Composites of yttria or ceria-partially-stabilized zirconia with layers of either alumina or a mixture of 50% by volume of alumina and zirconia were fabricated by sequential centrifuging of powder suspensions. This method allowed formation of layers with thickness of 10 to 70 μm. In both cases (Y-ZrO2 and Ce-ZrO2 matrices), a significant increase in fracture toughness, work of fracture and bending strength was observed only for composites with barrier layers made of a pure alumina. A crack deflection in alumina layer was found to be the main mechanism responsible for an increase in mechanical properties. For confirmation this thesis, no increase in the transformation zone width was observed. As it was shown, crack deflection angle was dependent on alumina layer thickness. Higher deflection angles for a thicker alumina layers were found. Explanation of this phenomenon was given by determination of residual stress distribution in barrier layers made by piezospectroscopy. A correlation between the crack deflection angle and the difference of stress between the layer boundary and the centre of the layer was noticed. The residual stresses observed are a result of thermal expansion mismatch between alumina and zirconia and thermal anisotropy of alumina. Shrinkage mismatch, especially in the case of Ce-ZrO2 and Al2O3, as a third source of stress is suggested. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) of the control and mechanically injured spinal cord of a rat in vitro and in vivo are reported. In vitro experiments were done on a home-built 6.4 T magnetic resonance microscope. Results for formaline-fixed samples show significant differences in diffusion tensor components between gray matter and white matter of the control spinal cord. Moreover, it is shown that already 6–10 min after the injury DTI can detect changes in water diffusion in areas extending far beyond the region of primary tissue damage. In vivo experiments were performed using a 9.4 T Magnex magnet and Bruker Medspec imaging system. Good-quality DTI images, free from motion artifacts were obtained. Results from control samples confirm differences in water diffusion between white matter and gray matter, observed in vitro. In vivo experiments show that characteristic changes in water diffusion observed in vitro 6–10 min after injury are preserved 60–360 min after injury, without significant alteration during this time. [ABSTRACT FROM AUTHOR]

The leaching activity of five batches of Thiobacillus ferrooxidans, strain F26-77, cultivated under various conditions, towards elemental sulphur, ferrous ions, pyrite, covellite, chalcopyrite and sphalerite was studied. The activities of sulphite oxidase, thiosulphate oxidase and rhodanese were determined in crude, cell-free bacterial extracts. The effectiveness of leaching was directly correlated with the enzymic activity of the cultures. The results suggest that the activities of the enzymes metabolizing sulphur and its inorganic compounds in Thiobacillus ferrooxidans, or bacterial leaching activity on sulphur and sulphides, rather than the rate of oxidation of ferrous ions, should be taken as the criterion of usefulness for the leaching of sulphide minerals. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was initial evaluation of applicability of metal organic framework (MOF) Fe-MIL-101-NH2 as a theranostic carrier of antituberculous drug in terms of its functionality, i.e. drug loading, drug dissolution, magnetic resonance imaging (MRI) contrast and cytotoxic safety.Methods: Fe-MIL-101-NH2 was characterized using X-ray powder diffraction, FTIR spectrometry and scanning electron microscopy. The particle size analysis was determined using laser diffraction. Magnetic resonance relaxometry and MRI were carried out on phantoms of the MOF system suspended in polymer solution. Drug dissolution studies were conducted using Franz cells. For MOF cytotoxicity, commercially available fibroblasts L929 were cultured in Eagle’s Minimum Essential Medium supplemented with 10% fetal bovine serum.Results: MOF particles were loaded with 12% of isoniazid. The particle size (3.37-6.45 μm) depended on the micronization method used. The proposed drug delivery system can also serve as the MRI contrast agent. The drug dissolution showed extended release of isoniazid. MOF particles accumulated in the L929 fibroblast cytoplasmic area, suggesting MOF release the drug inside the cells. The cytotoxicity confirmed safety of MOF system.Conclusions: The application of MOF for extended release inhalable system proposes the novel strategy for delivery of standard antimycobacterial agents combined with monitoring of their distribution within the lung tissue. [ABSTRACT FROM AUTHOR]