Introduction. Cellulose nanocrystals (CNCs) as attractive natural materials,have numerous applications in the biomedical field. Their unique biomechanicalcharacteristics, surface chemistry, low cost and sustainable naturemake them an engaging alternative to conventional materials and potentiatetheir use as progressive material. Therefore, it is critical to evaluate thecytocompatibility and immunomodulatory properties of nCNCs, which havenot been completely explored. The objective of this study was to examinea dose-dependent effect of native (n)CNCs on cytotoxicity and proliferativeactivity of human peripheral blood mononuclear cells (PBMNCs) in vitro.Methods. PBMNCs, obtained from the healthy blood donors, were cultivatedwith nCNCs. Cell viability was analyzed by flow cytometry assay, whileproliferative activity was determined by MTT, [3H]-thymidine uptake assayand detection of IL-2 production.Results. The cytotoxicity results suggested that no concentration of nCNCs(50-400 μg/ml) affected necrosis of PBMNCs, whereas apoptosis was inducedby the highest concentration of nCNCs compared to control (p<0.05).Unexpectedly, the highest concentration of nCNCs increased the metabolicactivity of PHA-stimulated cells compared to control (p<0.05). In contrastto these findings, lower concentrations of nCNCs (50 μg/ml and 100 μg/ml)stimulated proliferation of PBMNCs (p<0.05 and p<0.001). It was followedby increased production of IL-2 (100 μg/ml) (p<0.001).Conclusion. The results suggest that non-cytotoxic concentrations of nCNCsmodulate the proliferative activity of human PBMNCs, a phenomenon whichhas not been published up to now and which is relevant for further studies.

Introduction. Human monocytes are heterogeneous and plastic cell population with the ability to undergo phenotypic and functional changes as a response to a stimulus from a local microenvironment. Our aim was to determine the potential of human monocytes to differentiate into different cell populations depending on two different cytokines (IL-4 and IL-6) added to cultures as well as to compare their phenotypical and functional characteristics. Methods. Peripheral blood mononuclear cells (PBMNC) were isolated from buffy coats of healthy donors. Monocytes, which were separated from PBMNC by plastic adherence, had been cultivated in Dendritic cell (DC), serum free medium for 5 days, either with granulocyte/macrophage colony-stimulating factor (GM-CSF) alone or with GM-CSF, with addition of interleukin 4 (IL-4) or interleukin 6 (IL-6), respectively. After cultivation, phenotypic characteristics of these cells were analyzed by flow cytometry, whereas the levels of produced cytokines in culture supernatants were quantified by ELISA. The potential of differentiated cells to modulate the proliferation of allogeneic T cells was examined by co-cultivation of these cells with PBMNC. Results. GM-CSF differentiated monocytes into M0/M1 macrophages (MØ). The combination of GM-CSF and IL-4 favoured differentiation of immature DC, whereas GM-CSF and IL-6 transformed monocytes into monocytic myeloid derived suppressor cells (M-MDSC). All cell populations expressed typical monocyte/macrophage markers such as CD14, CD11b, CD16 and CD33, HLA-DR, CD209 and CD86, a co-stimulatory marker. DC and M-MDSC expressed CD1a and CD11c, in contrast to M0/M1 MØ. The expression of HLA-DR, CD1a, CD209 and CD86 was highest on DC. The expression of CD33 and CD16 was highest on M-MDSC, followed by lowest expression of HLA-DR. The potential of promoting T-cell proliferation was highest in cultures of PBMNC with DC, whereas M-MDSC had the opposite, suppressive, effect. These differences correlated with highest production of immunosuppressive cytokines such as IL-10, IL-27 and TGF-b by M-MDSC. Conclusion. This study confirmed the differentiation plasticity of human monocytes, which are influenced by cytokines added in cultures. Phenotypic characteristics of these cells correlated with the production of cytokines involved in modulation of T-cell proliferation.

Earnings management literature extensively explores tax regime and debt contracting as possible incentives in financial reporting. Firms engage with aggressive financial reporting to bias earnings in periods when the need for external financing increases. Contrary to this, the tax burden represents incentive for more conserva tive reporting. We argue that the level of firm’s financial reporting aggressiveness is not constant but rather floating from period to period, directly affecting the quality of financial reports. We assume that firm’s management on its own discretion determines the level of conservatism, balancing between these two incentives. The prevailing of two incentives, the need for external financing and the tax burden, determines the level of conservatism in particular reporting period. We hypothesised that the reduction in tax burden incentive overcomes the debt contracting incentive in the years of decreasing external financing need, implying more conservative accounting to balance between economic and taxable income. The total accruals are used as a measure of earnings management reflected to working capital accruals. The data analysis conducted on financial reports of 297 firms in the time-series of five years shows a significant correlation between total accruals, external financing needs and difference between economic and taxable income. This study provides an evidence on the association between conditional conservatism and external financing needs against anticipated tax sheltering activities in the economy with rather weak legal enforcement and widely spread use of accoun-ting-based covenants in debt contracting, proposing that the conditional conservatism may rather not reduce the cost of debt with the diminishing role of accounting in the debt contracting.

Context Neoangiogenesis and lymphangio-genesis are essential for the growth of tumor and progression of malignancy. Objective The study examined the significance of VEGF-C expression in comparison to classical prognostic factors in differentiated thyroid carcinoma (DTC), as well as an independent prognostic marker in DTC. Design The study included 81 patients with DTC allocated in two groups according to the type of cancer (follicular versus papillary) and then compared to expression of VEGF-C and clinicopathological features. Methods Expression of VEGF-C was identified with anti-VEGF-C antibody using tris-EDTA buffer Antigen Retrieval Protocol. Each specimen was scored with a semi-quantitative score system (H-score). Results The analysis of T staging system showed a linear correlation between the size of a tumor, expression of VEGF-C and recurrence of a disease, with a statistical significance (p < 0.0001). There was a clear and significant correlation between VEGF-C expression and T stage in patients with papillary carcinoma (p = 0.0294). Analysis of invasion of a surgical margin demonstrated significant positivity in patients with papillary thyroid cancers who expressed VEGF-C (p = 0.0207) indicating the worse prognosis of a disease. Also a statistically significant correlation was between VEGF-C and extrathyroid extension, indicating the worse prognosis (p = 0.0133) in papillary cancers. The level of VEGF-C expression was statistically significant in patients with papillary thyroid cancer (p = 0.039). Conclusions This study undoubtedly demonstrates that VEGF-C expression is an evident negative prognostic factor in patients with papillary thyroid carcinoma, along with the classic prognostic factors, such as a larger tumor size, tumor margin involvement, extrathyroid extension, i.e. local aggressiveness.

To keep internet based services available despite inevitable local internet and power outages, their data must be replicated to one or more other sites. For most systems using the store-and-forward architecture, data loss can also be prevented by using end-to-end acknowledgements. So far we have not found any sufficiently good solutions for replication of data in store-and-forward systems without acknowledgements and with geographically separated system nodes. We therefore designed a new replication protocol, which could take advantage of the lack of a global order between the messages and the acceptance of a slightly higher risk for duplicated deliveries than existing protocols. We tested a proof-of-concept implementation of the protocol for throughput and latency in a controlled experiment using 7 nodes in 4 geographically separated areas, and observed the throughput increasing superlinearly with the number of nodes up to almost 3500 messages per second. It is also, to the best of our knowledge, the first replication protocol with a bandwidth usage that scales according to the number of nodes allowed to fail and not the total number of nodes in the system.

One of the frequently occurring tasks during the development of warehouse management systems is the implementation of routing algorithms of some kind. Whether it is for routing workers during order picking, delivery vehicles or company representatives, this task has proven to be challenging in the technical as well as the social sense. In other words, the task is heavily dependent on various general and company-specific constraints and it directly dictates the way employees should do their job. This paper describes a strategic approach to the development and gradual integration of such algorithms which makes sure that all constraints are satisfied and, more importantly, ensures that route suggestions are viewed by the employees as a helpful tool rather than a threat to their job. In the first part of this paper, the approach is described and evaluated on a warehouse representative routing problem through a real-world case study in a medium-to-large warehouse. In the second part, the same approach is adapted to a delivery vehicle routing problem for a smaller retailer company. In both cases, routing efficiency almost doubled in comparison to previous approaches used by the companies. The most important factors of the implementation and integration stages as well as the impact of the changes on employee satisfaction are aggregated, analysed in detail, and discussed throughout different stages of development.

Studies that have investigated soil carbon dynamics under Mediterranean conditions are scarce and fragmented and contrasting results have often been reported. This study aimed to fill some gaps in our knowledge by: (i) determining annual dynamics of total (RS) and heterotrophic (RH) soil respiration; (ii) estimating annual cumulative RS and RH; and (iii) investigating the relationships between RS and RH and soil temperature and water content. The study was carried out in central Italy, for a plain and a hilly site, with the focus on two main cropping systems: an alfalfa-based forage system and a wheat-based rotation system. RS and RH showed different dynamics, with spatial and temporal variability across these sites. Estimated annual cumulative RS fluxes were 8.97 and 7.43 t C ha –1 yr–1 for the plain and hilly alfalfa-based sites, respectively, and 4.67 and 5.22 t C ha–1 yr–1 for the plain and hilly wheat-based sites, respectively. The RH components of RS were 4.26 and 3.52 t C ha –1 yr–1 for the plain and hilly alfalfa-based sites, respectively, and 3.89 and 2.45 t C ha–1 yr–1 for the plain and hilly wheat-based sites, respectively. A model with a combination of soil temperature and soil water content explained 43 % to 49 % and 33 % to 67 % of the annual variation of RS and RH, respectively. These findings help to extend our knowledge of Mediterranean cropping systems, although further studies are needed to clarify the effects of management practices on the modelling of soil respiration efflux.