Genetically modified natural killer cells specifically recognizing the tumor-associated antigens ErbB2/HER2 and EpCAM

The continuously growing natural killer (NK) cell line NK-92 is highly cytotoxic against malignant cells of various origin without affecting normal human cells. Based on this selectivity, the potential of NK-92 cells for adoptive therapy is currently being investigated in phase I clinical studies. To further enhance the antitumoral activity of NK-92 cells and expand the range of tumor entities suitable for NK-92-based therapies, here by transduction with retroviral vectors we have generated genetically modified NK-92 cells expressing chimeric antigen receptors specific either for the tumor-associated ErbB2 (HER2/neu) antigen or the human Epithelial Cell Adhesion Molecule (Ep-CAM). Both antigens are overexpressed by many tumors of epithelial origin. The chimeric antigen receptors consist of either the ErbB2 specific scFv(FRP5) antibody fragment or the Ep-CAM specific scFv(MOC31), a flexible hinge region derived from CD8, and transmembrane and intracellular regions of the CD3 zeta chain. Transduced NK-92-scFv(FRP5)-zeta or NK-92-scFv(MOC31)-zeta cells express high levels of the fusion proteins on the cell surface as determined by FACS analysis. In europium release assays no difference in cytotoxic activity of NK-92 and transduced NK-92 cells towards ErbB2 or Ep-CAM negative targets was found. However, even at low effector to target ratios transduced NK-92 cells specifically and efficiently lysed established ErbB2 or Ep-CAM expressing tumor cells that were completely resistant to cytolytic activity of parental NK-92 cells. Similarly, ErbB2-positive primary breast cancer cells isolated from pleural effusions of patients with recurrent disease were selectively killed by NK-92-scFv(FRP5)-zeta. In an in vivo model in immunodeficient mice treatment with retargeted NK-92-scFv(FRP5)-zeta, but not parental NK-92 cells resulted in markedly delayed growth of ErbB2 transformed cancer cells. These results demonstrate that efficient retargeting of NK-92 cytotoxicity can be achieved, and might allow the generation of potent cell-based therapeutics for the treatment of ErbB2 and Ep-CAM expressing malignancies. This therapeutic approach might be applicable for a large variety of different cancers where suitable cell surface antigens have been identified

The use of linear lighting in led technology - types of linear composition in residential interiors

Oświetlenie w technologii LED staje się coraz popularniejsze. Jednym z najczęściej wykorzystywanych jego typów są paski lub moduły zawierające diody LED, czyli elementy liniowe. Stwarzają one nowe możliwości kreowania oświetlenia wewnętrznego oraz umożliwiają różne sposoby jego implikacji. Artykuł dotyczy problematyki zastosowania oświetlenia liniowego w technologii LED we wnętrzach rezydencjonalnych. Przybliża problemy kompozycji tworzonych za pomocą oświetlenia liniowego zarówno w płaszczyznach pionowych, jak i poziomych. Zwraca także uwagę na rosnącą popularność tego typu rozwiązań. Porusza ponadto problem temperatury barwowej oświetlenia, a także jej oddziaływania na człowieka.Lighting in LED technology is becoming more and more popular. One of the most frequently used types are strips or modules containing LEDs, i.e. linear elements. LEDThey create new possibilities of creating internal lighting and enable various ways of its implications. The article concerns the issues of using linear lighting in LED technology in residential interiors. It deals with the problems of compositions created with the use of linear lighting in both vertical and horizontal planes. It also draws attention to the growing popularity of this type of solutions. It also touches upon the problem of the color temperature of lighting and its impact on humans

Selected aspects in the design of school and kindergarten buildings - the issues of reconstruction and extension of existing facilities - the case study of the SP13 complex in Gliwice

W artykule poruszono problematykę przebudowy budynków szkolnych i przedszkolnych wobec uwarunkowań lokalnych oraz konserwatorskich. Odwołano się do teorii projektowania budynków oświatowych i skonfrontowano z możliwościami wdrażania rozwiązań modelowych w zastanym kontekście. Omówiono przykład wieloetapowej przebudowy i rozbudowy zespołu szkolno-przedszkolnego o ponad stuletniej historii znajdującego się w Gliwicach. Wskazano uwarunkowania oraz wady i zalety rozwiązań projektowych. Autorzy, będący projektantami próbują odpowiedzieć na pytanie, czy rozwiązania modelowe są wystarczająco uniwersalne by stosować je niezależnie od kontekstu, czy wręcz przeciwnie.The article describes the issues of reconstruction of school and kindergarten buildings in terms of local and conservation conditions. The theory of educational buildings design has been referred and confronted with the possibilities of implementing model solutions in the given context. An example of a multi-stage reconstruction and extension of a school and kindergarten complex located in Gliwice with over a hundred years of history has been discussed. Conditions as well as advantages and disadvantages of design solutions have been indicated. The authors, who are designers, try to answer the question whether the model solutions are universal enough to be used regardless of the context, or on the contrary

Revitalization opportunities case study of wedding palace in Sosnowiec on the background of selected modernist pavilions from the 1960’s and 1970’s

Wśród obiektów modernistycznych wznoszonych w Polsce w latach 60. i 70. XX wieku można wyodrębnić wyjątkową grupę - typ zabudowy pawilonowej realizującej w pełni 5 zasad architektury modernistycznej Le Corbusiera. W artykule przedstawiono wybrane przykłady takich budynków oraz zwrócono uwagę na stan ich zachowania i stopień przekształcenia względem pierwotnej formy oraz funkcji. Przedstawiono szerzej przypadek najbardziej drastycznego braku poszanowania istniejącego obiektu, jakim jest przebudowa Pałacu Ślubów w Sosnowcu, oraz autorską propozycję przywrócenia obiektu do stanu pierwotnego.Among the modernist buildings erected in Poland in the 1960s and 1970s, we can distinguish a unique group - a type of pavilion development, fully implementing the 5 principles of Le Corbusier's modern architecture. The article presents selected examples of such buildings and highlights the state of their preservation and the degree of transformation in relation to their original form and function. The case of the most drastic lack of respect for the existing building, which is the reconstruction of the Wedding Palace in Sosnowiec, and the original proposal to restore the building to its original state are presented in more detail

Renovation And Modernization Of Hotel Buildings - Case Studies In Silesia

The cultural heritage of Silesia has different backgrounds and is often characterized by difficult to assess values. There is doubt as to whether some of the existing buildings should be modernized. Since 2000, an increase in the amount of investments in hotel buildings and conference venues in Poland has been observed. The functions and roles of hotels within a city have also changed. The paper presents examples of original projects and realizations of hotel buildings in Silesia. A discussion was also held regarding the issue of adapting and modernizing hotel buildings

Energy-Active Shadow Structures in Single-Family Buildings – Application Possibilities and Architectural Conditions

Existing approaches to indoor environmental quality in single-family residential buildings have been described, identifying their optimal preferred parameters for maintaining a human-healthy environment. The energy requirements for maintaining basic building systems (lighting, cooking, heating, ventilation, cooling) have been analyzed. Passive and active sources of energy production have been analyzed, prosumer buildings have been considered, and methods of obtaining maximum energy in winter periods and avoiding overheating of the building in summer periods have been discussed. Process schemes of using active shadow structures as an integral element with other systems acquiring energy from RES in single-family residential buildings have been presented. Architectural aspects of the use of energy-active shadow structures in residential buildings (single – family houses) have been presented together with alternative solutions. This paper presents process diagrams of the use of energy-active shadow integrated with other renewable energy sources used in single-family buildings, such as: BIPV, PVT and heat pumps, benefiting indoor environmental quality. Architectural considerations for the use of energy-active shadow structures in single-family homes have been presented along with alternative solutions. The purpose of this paper is to present a concept (especially effective in the summer) for an additional way to harvest electricity from energy-active shadows in single-family houses

Resilient university campus in the city in COVID and post‐COVID era—recommendations, guidelines, and evidence from research in Italy and Poland

The pandemic ‘stay at home’ obligations turned our homes from a place to live to a place to live, work, entertain ourselves and to study. Since March 2020, confinement has had a permanent impact on students’ perception of studying and on academic lifestyle. Most universities continue teaching online, and most academic facilities, such as lecture and seminar halls, student halls, and dormitories, have been abandoned. Some of them form vast areas in cities that play a major role in the urban structure. The authors have examined the degree and way of occupation of the academic infrastructure before and in time of the pandemic. Evidence and data have been gathered from different universities in Poland and Italy. From their origins, academic campuses can be considered autonomous communities within or on the city limits. In a post-pandemic perspective, the evidence shows that the growing population of students does not mean campus development and that the campuses that have shown the greatest resilience are “open” campuses which are able to share, integrate, and exchange their spaces and facilities with those of the city. The authors conclude that the pandemic will have an impact on the future urban form of academic facilities

Inhibition of NF-kappa B potentiates amyloid beta-mediated neuronal apoptosis

Kaltschmidt B, Uherek M, Wellmann H, Volk B, Kaltschmidt C. Inhibition of NF-kappa B potentiates amyloid beta-mediated neuronal apoptosis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 1999;96(16):9409-9414.One mechanism leading to neurodegeneration during Alzheimer's disease (AD) is amyloid beta peptide (A beta) neurotoxicity. A beta elicits in cultured central nervous system neurons a biphasic response: a low-dose neurotrophic response and a high-dose neurotoxic response. Previously me reported that NF-kappa B is activated by low doses of A beta only. Here we show that NF-kappa B activation leads to neuroprotection. In primary neurons me found that a pretreatment with 0.1 mu M A beta-(1-40) protects against neuronal death induced with 10 mu M A beta-(1-40). As a known neuroprotective agent we nest analyzed the effect of tumor necrosis factor alpha (TNF-alpha). Maximal activation of NF-kappa B was found with 2 ng/ml TNF-alpha. Pretreatment with TNF-alpha protected cerebellar granule cells from tell death induced by 10 mu M A beta-(1-40). This protection is described by an inverted U-shaped dose response and is maximal with a NF-kappa B-activating dose. The molecular specificity of this protective effect was analyzed by specific blockade of NF-kappa B activation. Overexpression of a transdominant negative I kappa B-alpha blocks NF-kappa B activation and potentiates A beta-mediated neuronal apoptosis. Our findings show that activation of NF-kappa B is the underlying mechanism of the neuroprotective effect of low-dose A beta and TNF-alpha. In accordance with these in vitro data we find that nuclear NF-kappa B immunoreactivity around various plaque stages of AD patients is reduced in comparison to age-matched controls, Taken together these data suggest that pharmacological NF-kappa B activation may be a useful approach in the treatment of AD and related neurodegenerative disorders

Transcription factor NF-kB is activated in primary neurons by amyloid ß peptides and in neurons surrounding early plaques from patients with Alzheimer disease

Kaltschmidt B, Uherek M, Volk B, Baeuerle PA, Kaltschmidt C. Transcription factor NF-kB is activated in primary neurons by amyloid ß peptides and in neurons surrounding early plaques from patients with Alzheimer disease. Proc. Natl. Acad. Sci. USA. 1997;94(6):2642-2647