Criteria and methods of optimization of unprofitable enterprise’s financial architecture

Розкрито сутність механізму оптимізації фінансової архітектури збиткового підприємства. Визначено критерії та методи оптимізації фінансової архітектури збиткового підприємства.Essence of mechanism of optimization of unprofitable enterprise’s financial architecture of is exposed. Criteria and methods of optimization of unprofitable enterprise’s financial architecture are defined

Global Activation of CD8+ Cytotoxic T Lymphocytes Correlates with an Impairment in Regulatory T Cells in Patients with Generalized Vitiligo

Melanocyte-specific CD8+ cytotoxic T lymphocytes (CTLs) play a pivotal role in vitiligo-induced depigmentation. Yet, the mechanisms underlying the high frequency of generalized autoimmune disorders associated with generalized vitiligo (GV) are unknown. We hypothesized that an imbalance between activated CD8+ CTLs and regulatory T cells (Tregs) exists in patients with GV . Assessment of the circulating CD8+ CTLs and Tregs by flow cytometric analysis revealed an obvious expansion of CD8+ CTLs and a concomitant decrease in Treg cells in GV patients. The percentages of skin infiltrating CD8+ CTLs and Tregs were evaluated by immunohistochemistry and revealed dramatically increased numbers of both CD8+ CTLs and Tregs in the perilesional skin of GV patients. However, peripheral Tregs were impaired in their ability to suppress the proliferation and cytolytic capacity of autologous CD8+ T cells, suggesting that a functional failure of Tregs and the hyper-activation of CD8+ CTLs may contribute to progressive GV. Our data indicate that reduced numbers and impaired function of natural Tregs fail to control the widespread activation of CD8+ CTLs, which leads to the destruction of melanocytes and contributes to the elevated frequency of various associated autoimmune diseases. This knowledge furthers our understanding of the mechanisms of immune tolerance that are impaired in GV patients and may aid in the future development of effective immunotherapy for GV patients

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis.In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo.These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses

Market Intelligence - ujęcie konceptualne

Nowadays the biggest challenge for managers is obtaining business information that should support decision-making processes. The main task of decision makers is to understand the operating environment in order to compete effectively and as a result, to achieve success and development. Market intelligence as a practical program collects information about the market and its players through constant monitoring of the environment and ongoing changes that are observed, as well as in a form of ad hoc projects. Nowadays market intelligence in many companies has reached a position that compares to other professional management support functions, such as risk management or public relations. The aim of the article was to provide an explanation of the essence of market intelligence as a concept that plays a crucial role in generating valuable knowledge about the market, building competitiveness of enterprises and achieving growth in a specific market. The authors present the results of introductory research on functioning of programs used for obtaining knowledge about the market in regional enterprises. The research was conducted in big and medium-sized enterprises in Lodz province by means of a personal interview and a measurement tool was a questionnaire.W dzisiejszych czasach wyzwaniem dla menedżerów jest pozyskiwanie szeroko rozumianej informacji biznesowej służącej wsparciu procesów decyzyjnych. Zadaniem decydentów jest rozumieć otoczenie, w którym funkcjonuje organizacja, skutecznie konkurować, a w rezultacie osiągać sukces i rozwój. Market intelligence jako praktyczny program działań umożliwia pozyskanie informacji o rynku i jego uczestnikach, poprzez ciągłe monitorowanie otoczenia i bieżących zmian, które w nim zachodzą, jak również w formie projektów realizowanych ad hoc. Obecnie market intelligence osiąga w wielu organizacjach pozycję porównywalną do pozycji innych funkcji wspierających procesy zarządcze, takich jak zarządzanie ryzykiem czy public relations. Celem artykułu było wyjaśnienie istoty market intelligence, jako koncepcji pełniącej krytyczną rolę w generowaniu wartościowej wiedzy o rynku, budowaniu konkurencyjności przedsiębiorstwa oraz osiąganiu wzrostu na obsługiwanym rynku. Przedstawione zostały także wyniki wstępnych badań na temat funkcjonowania programów pozyskiwania wiedzy o rynku w rodzimych przedsiębiorstwach. Badanie przeprowadzono wśród dużych i średnich przedsiębiorstw województwa łódzkiego, za pomocą metody wywiadu osobistego, a narzędziem pomiaru był kwestionariusz wywiadu

A symbiotic concept of autoimmunity and tumour immunity: lessons from vitiligo

Vitiligo is a skin disease in which melanocytes (MCs) are eradicated from lesional epidermis, resulting in disfiguring loss of pigment. MCs are destroyed by MC-reactive T cells, as well as other non-immune and immune components. Similarities exist between the autoimmunity observed in vitiligo and the tumour immunity observed in melanoma immuno-surveillance. An analysis of these mechanisms might lead to the development of new therapies for both vitiligo and melanom

Crystal Structure of Kluyveromyces lactis Glucokinase KlGlk1

Glucose phosphorylating enzymes are crucial in the regulation of basic cellular processes, including metabolism and gene expression. Glucokinases and hexokinases provide a pool of phosphorylated glucose in an adenosine diphosphate (ADP)- and ATP-dependent manner to shape the cell metabolism. The glucose processing enzymes from Kluyveromyces lactis are poorly characterized despite the emerging contribution of this yeast strain to industrial and laboratory scale biotechnology. The first reports on K. lactis glucokinase (KlGlk1) positioned the enzyme as an essential component required for glucose signaling. Nevertheless, no biochemical and structural information was available until now. Here, we present the first crystal structure of KlGlk1 together with biochemical characterization, including substrate specificity and enzyme kinetics. Additionally, comparative analysis of the presented structure and the prior structures of lactis hexokinase (KlHxk1) demonstrates the potential transitions between open and closed enzyme conformations upon ligand binding