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The article presents the test results on the technology of surface hardening of castings from unalloyed and low-alloy nodular cast iron using the method of surface heat treatment, i.e., induction surface hardening and methods of thermochemical treatment, i.e. gas nitriding, nitrocarburizing, and nitrocarburizing with oxidation. The scope of research included macro- and microhardness measurements using Rockwell and Vickers methods, respectively, as well as metallographic microscopic examinations using a light microscope. Furthermore, abrasive wear resistance tests were performed using the pin-on-disk method in the friction pair of nodular cast iron – SiC abrasive paper and the reciprocating method in the friction pair of nodular cast iron – unalloyed steel. Analysis of the test results shows that the size and depth of surface layer hardening strongly depend on the chemical composition of the nodular cast iron, determining its hardenability and its ability to create diffusion layers. Medium induction surface hardening made it possible to strengthen the surface layer of the tested nodular cast irons to the level of 700 HV0.5 with a hardening depth of up to approximately 4000μm, while various variants of thermochemical treatment provided surface hardness of up to 750 HV0.5 with a hardening depth of up to approximately 200μm. Furthermore, induction surface hardening increased the resistance to abrasive wear of nodular cast iron castings, depending on the test method, by an average of 70 and 45%, while thermochemical treatment on average by 15 and 60%.

IntroductionTo cope with catastrophic floods, people need to be better prepared. In this context, a self-assessment digital tool for habitat vulnerability was developed. To improve its take-up rate, we are looking at the motivations associated with the social acceptability of this tool. The motivations (hedonic—gain—normative), derived from goal-frame theory, as well as elements relating to risk perception, are tested.MethodOne, 688 participants (aged between 18 and 87) first read a scenario presenting the application (reflecting either one of the motivations of the Goal Framing Theory or a control scenario with no motivation). After reading one of the scenarios, they completed an online questionnaire, measuring the acceptability of the tool using three measures: a direct one (items from the Technological Acceptability Model: ease of use, perceived usefulness and social influence), an indirect measure (by asking the percentage of neighbours interested in the tool) and a social measure (judgement of a person using the tool). The last part of the questionnaire was about subjects’ risk perception.ResultsThe analyses show that, of all the scenarios, the one involving hedonic motivation leads to the lowest social acceptance of the tool. We also observe that a better risk perception predicts better tool acceptability. Finally, we observe interaction effects between risk perception and motivations, showing that normative motivation is better when risk perception increases and that the control condition is better when risk perception decreases.DiscussionGoal framing theory is usually used for ecological behaviors. It also appears here as relevant in the field of risk prevention. Although risk perception remains the best predictor of acceptability, these results lead us to conclude that hedonic motivation is not appropriate for the acceptability of a flood risk prevention tool. It is preferable to focus on normative and gain motivations.

PURPOSE: This study explores the relationship between the resilience of the hotel industry (an underdeveloped concept) and the factors that support the development of this industry. It examines whether the resilience of the hotel industry varies regionally and whether it is influenced either by the characteristics of the hotel industry or by regional economic conditions. The study focuses on the COVID-19 pandemic, which particularly hit the hotel industry. METHODOLOGY: The clustering method is used to identify regions in Poland with similar pre-pandemic hotel industry development are identified. Secondly, Potthoff’s analysis and Kruskal-Wallis tests with Dunn’s tests are used respectively to identify variations in the resilience responses of the industry in different regions and to examine the antecedents of these variations. FINDINGS: The data collected indicate variations between clusters in terms of resilience response. Not all factors that support the development of the hotel industry in a particular region are equally conducive to its resilience. Our study shows that the pandemic was not an isolated or unique event but rather a catalyst that brought long-standing issues for the hotel and tourism sector. IMPLICATIONS FOR THEORY AND PRACTICE: This study contributes to the development of resilience theory by providing evidence-based arguments for separating the domains of resilience and development and for a more granular exploration of the trade-offs between them. From the perspective of the hotel industry, insights into narrowly channeled agglomeration externalities during a crisis could inform strategic decisions regarding the location of hotel investments, the value proposition created, and business model diversification. Therefore, there is a need for more resilient crisis management strategies that can be applied across the tourism sector. These strategies should encompass effective supply chain management and a robust framework for labor security. ORIGINALITY AND VALUE: The findings suggest that hotel industry development factors, which include both industry characteristics and regionally shaped economic conditions, provide mixed support for the resilience of this industry. The study revealed clear tensions between development and resilience impacts by highlighting existing trade-offs. Focusing attention on trade-off tensions advances both the conceptual validity and application potential. Although the present study was defined for the specific circumstances of the hotel industry, this approach can be replicated in different industries that are components of the supply chain of the tourism market and its value chain.

Sytuacje mogące powodować uraz psychiczny takie jak przemoc, zaniedbanie i dysfunkcje rodziny dotykają istotną część dzieci. Odczuwanie zagrożenia w bliskiej relacji połączone z niedostępnością responsywnego dorosłego łagodzącego negatywne emocje dziecka prowadzi do pojawienia się toksycznego stresu (toxic stress) negatywnie wpływającego na rozwój mózgu. Stąd dzieci z historią traumy mogą w szkole przejawiać różnorodne problemy, w tym deficyt uwagi, nadaktywność i dysregulację emocji. Jednocześnie zagrażające doświadczenia w dzieciństwie (adverse childhood experiences) sprzyjają rozwojowi pozabezpiecznych stylów przywiązania, przez co dziecko znajdując się w środowisku szkolnym może z trudem ufać nauczycielom, czuć dużą presję i interpretować zachowania innych w kategoriach zagrożenia, ale też przeżywać silną frustrację w sytuacji niepowodzeń i mieć trudności w rozwiązywaniu konfliktów. Najpoważniejsze konsekwencje ma zdezorganizowany wzorzec więzi. Trudności uczniów z historią traumy wymagają specyficznej odpowiedzi ze strony szkół, stąd powstał postulat edukacji wrażliwej na traumę (trauma-informed education). Z teorii przywiązania wynika, że w szkole najpierw należy zapewnić dziecku poczucie bezpieczeństwa emocjonalnego, przede wszystkim dzięki relacji z nauczycielem, który w obliczu problematycznych reakcji ucznia rozumie jego specyficzne potrzeby i aktywnie podtrzymuje z nim wymianę emocjonalną.

Chimeric antigen receptor (CAR) T cell therapies targeting B cell-restricted antigens CD19, CD20, or CD22 can produce potent clinical responses for some B cell malignancies, but relapse remains common. Camelid single-domain antibodies (sdAbs or nanobodies) are smaller, simpler, and easier to recombine than single-chain variable fragments (scFvs) used in most CARs, but fewer sdAb-CARs have been reported. Thus, we sought to identify a therapeutically active sdAb-CAR targeting human CD22. Immunization of an adult Llama glama with CD22 protein, sdAb-cDNA library construction, and phage panning yielded >20 sdAbs with diverse epitope and binding properties. Expressing CD22-sdAb-CAR in Jurkat cells drove varying CD22-specific reactivity not correlated with antibody affinity. Changing CD28- to CD8-transmembrane design increased CAR persistence and expression in vitro. CD22-sdAb-CAR candidates showed similar CD22-dependent CAR-T expansion in vitro, although only membrane-proximal epitope targeting CD22-sdAb-CARs activated direct cytolytic killing and extended survival in a lymphoma xenograft model. Based on enhanced survival in blinded xenograft studies, a lead CD22sdCAR-T was selected, achieving comparable complete responses to a benchmark short linker m971-scFv CAR-T in high-dose experiments. Finally, immunohistochemistry and flow cytometry confirm tissue and cellular-level specificity of the lead CD22-sdAb. This presents a complete report on preclinical development of a novel CD22sdCAR therapeutic.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the tumor suppressor genes TSC1 or TSC2. TSC is characterized by the formation of multiple tumors in various organs. The most common neurological manifestation of the disorder is epilepsy present in 79–90% of cases. At least one-third of TSC patients develop drug-resistant epilepsy (DRE) which remains a great challenge for clinicians. Neuromodulation is an option in cases of multifocal epilepsy, epilepsy originating in eloquent areas, or the inability to identify the ictal onset zone. Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) may be used in the treatment of multifocal DRE. Here, we present a case of a patient with multifocal DRE caused by TSC, who was treated with ANT-DBS. A follow-up period of eight months showed that the patient's multifocal DRE was successfully treated by ANT-DBS.

This paper describes the technology for the production of precursors (space holder material) used to form the complex internal structure of cast metal foam. The precursor material must exhibit sufficient refractoriness, resist contact with liquid metal and at the same time should exhibit good collapsibility after casting. With regard to the greening of foundry production, the focus of this paper was on materials that could exhibit the above properties and at the same time do not have a negative impact on the environment. In this paper, the technology for the production of spherical precursors from a self-hardening mixture with a geopolymer-based binder system is described and verified. The motivation for the choice of material and all the sub-steps of the process – molding into the core box, tumbling, including the necessary accompanying tests of the mechanical properties of the core mixture being verified – are described.

Abstract Blood brain barrier (BBB) models in vitro are an important tool to aid in the pre-clinical evaluation and selection of BBB-crossing therapeutics. Stem cell derived BBB models have recently demonstrated a substantial advantage over primary and immortalized brain endothelial cells (BECs) for BBB modeling. Coupled with recent discoveries highlighting significant species differences in the expression and function of key BBB transporters, the field is in need of robust, species-specific BBB models for improved translational predictability. We have developed a mouse BBB model, composed of mouse embryonic stem cell (mESC-D3)-derived brain endothelial-like cells (mBECs), employing a directed monolayer differentiation strategy. Although the mBECs showed a mixed endothelial-epithelial phenotype, they exhibited high transendothelial electrical resistance, inducible by retinoic acid treatment up to 400 Ω cm2. This tight cell barrier resulted in restricted sodium fluorescein permeability (1.7 × 10–5 cm/min), significantly lower than that of bEnd.3 cells (1.02 × 10–3 cm/min) and comparable to human induced pluripotent stem cell (iPSC)-derived BECs (2.0 × 10–5 cm/min). The mBECs expressed tight junction proteins, polarized and functional P-gp efflux transporter and receptor mediated transcytosis (RMT) receptors; collectively important criteria for studying barrier regulation and drug delivery applications in the CNS. In this study, we compared transport of a panel of antibodies binding species selective or cross-reactive epitopes on BBB RMT receptors in both the mBEC and human iPSC-derived BEC model, to demonstrate discrimination of species-specific BBB transport mechanisms.

Location is crucial when it comes to reducing the energy demand of buildings. Deterministic mathematical models of the energy demand of a single-family building were developed for the cities of Wrocław and Suwałki, representing the mild and severe climatic conditions of Poland, respectively, and compared with energy demand for Białystok, representing medium conditions. Models include the windows area, heat transfer coefficient, solar radiation transmittance of glazing, and orientation of windows. For medium conditions (Białystok), the energy demand is 18.3% higher than for mild conditions (Wrocław) and 7.3% lower than for severe climate conditions (Suwałki). Location does not influence the nature of the effect of the factors on energy demand, which increases with an increase in heat transfer coefficient and a decrease in window area, glazing solar radiation transmittance, and orientation change from north to south. The large impact of solar gains was proved. The optimisation procedure was performed and mathematical descriptions of recommended parameters were created to ensure the equivalent energy efficiency of windows for each orientation and location. For Bialystok, north-facing windows can have an area 1.32 times larger and south-facing windows 1.48 times smaller than east-facing windows to ensure a building’s energy demand remains constant.

The paper presents a comparison of three strain measurement methods. The mechanical parameters of S355 grade steel (yield strength, tensile strength, modulus of elasticity) were determined in tensile tests. Strains were measured using high resolution measuring instruments: an extensometer, a strain gauge and an ARAMIS 3D DIC system. In this paper, these three instruments have been used simultaneously in tensile tests for the first time. The results indicate that the values of the Young’s modulus obtained using different techniques were similar when each instrument measured strain on the same side of the sample. Small differences were connected with different gauge lengths and their locations. The values of the Young’s modulus determined on the opposite sides of the samples were more varied even when the same method was used (strain gauge measurements). For this reason, it is recommended to use double-sided averaging instruments when the Young’s modulus is determined. The strain-curves obtained from the strain gauge measurements were incomplete and they came to an end at the end of the yield plateau due to the fact that they were damaged when the values of strain were relatively high. The extensometer was used up to the point where the strain reached 0.3% and then the strain was measured based on the distance between the machine clamps. The stress-strain curves obtained from the DIC system were complete because the system was able to monitor the sample until the very end of the tests.

Purpose: The Covid-19 pandemic disrupted the lives of people and organizations, including supply chains (SC). Therefore, this study aims to explore concepts, methods, and tools for managing SC during the Covid-19 pandemic.

The article discusses benefits associated with the use of silicon carbide in the process of melting gray cast iron and ductile cast iron in induction electric furnaces. It presents the analysis of the impact of various charge materials and the addition of a variable amount of SiC and FeSi to the fixed charge when melting cast iron of grades GJS 400-15 and GJS 500-7 on mechanical properties and microstructure. Moreover, the article includes an analysis of the efficiency of carburization and the increase in the content of silicon during the application of SiC. The article also presents the results of the study of primary modification using silicon carbide at the minimum temperature of Temin eutectic and Tsol solidus. Based on analysis of the literature, conducted research, and calculations, it was found that the addition of silicon carbide has a beneficial impact on the properties of melted cast iron. The addition of SiC in the charge increases the content of C and Si without increasing the amount of contaminations. The addition of SiC at reduced pig iron presence in the charge decreases production costs, while the use of SiC as an inoculant increases both Temin and Tsol, which is beneficial from the point of view of cast iron nucleation.

Satysfakcja klientów z oferowanych im usług jest kluczowa dla sukcesu każdego przedsięwzięcia biznesowego, szczególnie w sektorze turystycznym. Celem niniejszego artykułu jest analiza satysfakcji klientów polskich hoteli i zweryfikowanie, czy cechy charakterystyczne obiektów hotelowych różnicują zadowolenie ich gości. Badanie oparte zostało na danych zebranych z 2036 profili hoteli dostępnych na portalu Booking.com metodą web-scrapingu oraz poddane analizie ANOVA i obliczeniu współczynnika korelacji Pearsona w programie SPSS. Analiza wykazała, że poziom usług oferowanych przez polskie obiekty hotelarskie jest na zadowalającym poziomie. Satysfakcję polskich klientów najbardziej różnicują: kategoria hotelu, przynależność do sieci hotelowej oraz długość funkcjonowania. Niewielki wpływ na satysfakcję wykazano dla lokalizacji obiektu i jego wielkości. Charakterystyczna dla polskiego rynku hotelowego okazała się wyższa satysfakcja z jakości usług oferowanych przez hotele sieciowe w porównaniu do hoteli niezależnych oraz podobny poziom satysfakcji z jakości personelu. Artykuł wskazuje także na elementy wymagające działań ze strony osób zarządzających obiektami hotelarskimi w celu podniesienia satysfakcji ze świadczonych usług.

Abstract Human blood brain barrier (BBB) models derived from induced pluripotent stem cells (iPSCs) have become an important tool for the discovery and preclinical evaluation of central nervous system (CNS) targeting cell and gene-based therapies. Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary form of gene-modified cell-based immunotherapy with potential for targeting solid tumors, such as glioblastomas. Crossing the BBB is an important step in the systemic application of CAR-T therapy for the treatment of glioblastomas and other CNS malignancies. In addition, even CAR-T therapies targeting non-CNS antigens, such as the well-known CD19-CAR-T therapies, are known to trigger CNS side-effects including brain swelling due to BBB disruption. In this study, we used iPSC-derived brain endothelial-like cell (iBEC) transwell co-culture model to assess BBB extravasation of CAR-T based immunotherapies targeting U87MG human glioblastoma (GBM) cells overexpressing the tumor-specific mutated protein EGFRvIII (U87vIII). Two types of anti-EGFRvIII targeting CAR-T cells, with varying tonic signaling profiles (CAR-F263 and CAR-F269), and control Mock T cells were applied on the luminal side of BBB model in vitro. CAR-F263 and CAR-F269 T cells triggered a decrease in transendothelial electrical resistance (TEER) and an increase in BBB permeability. CAR-T cell extravasation and U87vIII cytotoxicity were assessed from the abluminal compartment using flow cytometry and Incucyte real-time viability imaging, respectively. A significant decrease in U87vIII cell viability was observed over 48 h, with the most robust cytotoxicity response observed for the constitutively activated CAR-F263. CAR-F269 T cells showed a similar cytotoxic profile but were approximately four fold less efficient at killing the U87vIII cells compared to CAR-F263, despite similar transmigration rates. Visualization of CAR-T cell extravasation across the BBB was further confirmed using BBTB-on-CHIP models. The described BBB assay was able to discriminate the cytotoxic efficacies of different EGFRvIII-CARs and provide a measure of potential alterations to BBB integrity. Collectively, we illustrate how BBB models in vitro can be a valuable tool in deciphering the mechanisms of CAR-T–induced BBB disruption, accompanying toxicity and effector function on post-barrier target cells.