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Introduction: Primary human blood cells represent an essential model system to study physiology and disease. However, human blood is a limited resource. During healthy donor plateletpheresis, the leukoreduction system chamber (LRSC) reduces the leukocyte amount within the subsequent platelet concentrate through saturated, fluidized, particle bed filtration technology. Normally, the LRSC is discarded after apheresis is completed. Compared to peripheral blood, LRSC yields 10-fold mononuclear cell concentration. Methods: To explore if those retained leukocytes are attractive for research purposes, we isolated CD3+ T cells from the usually discarded LRSCs via density gradient centrifugation in order to manufacture CD19-targeted chimeric antigen receptor (CAR) T cells. Results: Immunophenotypic characterization revealed viable and normal CD4+ and CD8+ T-cell populations within LRSC, with low CD19+ B cell counts. Magnetic-activated cell sorting (MACS) purified CD3+ T cells were transduced with CD19 CAR-encoding lentiviral self-inactivating vectors using concentrated viral supernatants. Robust CD19 CAR cell surface expression on transduced T cells was confirmed by flow cytometry. CD19 CAR T cells were further enriched through anti-CAR MACS, yielding 80% CAR+ T-cell populations. In vitro CAR T cell expansion to clinically relevant numbers was achieved. To prove functionality, CAR T cells were co-incubated with the human CD19+ B cell precursor leukemia cell line Nalm6. Compared to unmodified T cells, CD19 CAR T cells effectively eradicated Nalm6 cells. Conclusion: Taken together, we can show that lymphocytes isolated from LRSCs of plateletpheresis sets can be efficiently used for the generation of functional CAR T cells for experimental purposes. [ABSTRACT FROM AUTHOR]

Based on the present value model for stock prices, we utilise a pooled mean group estimator for panel ARDL cointegration to estimate the long-run relationship between G7 stock prices and macroeconomic variables over the last 40 years. We find a positive long-run relation between stock prices, industrial production and consumer prices as well as a negative relationship with real 10-year interest rates.

Background: The oncological impact of perioperative blood transfusions (PBTs) of patients undergoing radical cystectomy (RC) because of bladder cancer (BCa) has been a controversial topic discussed in recent years. The main cause for the contradictory findings of existing studies might be the missing consideration of the storage time of red blood cell units (BUs), donor age, and gender matching. Study Design and Methods: We retrospectively analyzed BCa patients who underwent RC in our department between 2004 and 2021. We excluded patients receiving BUs before RC, >10 BUs, or RC in a palliative setting. We assessed the effect of blood donor characteristics and storage time on overall survival (OS) and cancer‐specific survival (CSS) through univariate and multivariable Cox regression analysis. We also performed a propensity score matching with patients who received BUs and patients who did not on a 1:1 ratio. Results: We screened 1692 patients and included 676 patients for the propensity score matching. In the multivariable analysis, PBT was independently associated with worse OS and CSS (p <.001). Postoperative transfusions were associated with better OS (p =.004) and CSS (p =.008) compared to intraoperative or mixed transfusions. However, there was no influence of blood donor age, storage time, or gender matching on prognosis. Discussion: In our study of BCa patients undergoing RC, we demonstrate that PBT, especially if administered intraoperatively, is an independent risk factor for a worse prognosis. However, storage time, donor age, or gender matching did not negatively affect oncological outcomes. Therefore, the specific selection of blood products does not promise any benefits. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has led to an unprecedented decline in global air transport and associated reduction in CO _2 emissions. The International Civil Aviation Organization (ICAO) reacted by weakening its own CO _2 -offsetting rules. Here we investigate whether the pandemic can be an opportunity to bring the sector on a reliable low-carbon trajectory, with a starting point in the observed reduction in air transport demand. We model a COVID-19 recovery based on a feed-in quota for non-biogenic synthetic fuels that will decarbonize fuels by 2050, as well as a carbon price to account for negative externalities and as an incentive to increase fuel efficiency. Results suggest that until 2050, air transport demand will continue to grow, albeit slower than in ICAO’s recovery scenarios, exceeding 2018 demand by 3.7–10.3 trillion RPK. Results show that synthetic fuels, produced by 14–20 EJ of photovoltaic energy, would make it possible to completely phase out fossil fuels and to avoid emissions of up to 26.5 Gt CO _2 over the period 2022–2050.

Background: Native cluster of differentiation (CD) 19 targeting antibodies are poorly effective in triggering antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are crucial effector functions of therapeutic antibodies in cancer immunotherapy. Both functions can be enhanced by engineering the antibody’s Fc region by altering the amino acid sequence (Fc protein-engineering) or the Fc-linked glycan (Fc glyco-engineering). We hypothesized that combining Fc glyco-engineering with Fc protein-engineering will rescue ADCC and CDC in CD19 antibodies. Results: Four versions of a CD19 antibody based on tafasitamab’s V-regions were generated: a native IgG1, an Fc protein-engineered version with amino acid exchanges S267E/H268F/S324T/G236A/I332E (EFTAE modification) to enhance CDC, and afucosylated, Fc glyco-engineered versions of both to promote ADCC. Irrespective of fucosylation, antibodies carrying the EFTAE modification had enhanced C1q binding and were superior in inducing CDC. In contrast, afucosylated versions exerted an enhanced affinity to Fcγ receptor IIIA and had increased ADCC activity. Of note, the double-engineered antibody harboring the EFTAE modification and lacking fucose triggered both CDC and ADCC more efficiently. Conclusions: Fc glyco-engineering and protein-engineering could be combined to enhance ADCC and CDC in CD19 antibodies and may allow the generation of antibodies with higher therapeutic efficacy by promoting two key functions simultaneously.

The author proposes a new approach for bridge crack detection by a 360° camera on top of a drone. Traditionally, bridge inspection is performed manually and although the use of drones has been implemented before, researchers used standard high definition cameras underneath the drone. To make the approach comparable to the conventional approach, two bridges were selected in Germany and inspected for cracks and defects by applying both methods. The author follows an engineering design process and after developing a prototype of the drone with a 360° camera above the body of the drone, the system is built, tested, and the bridges are inspected. First, the critical parts of the bridges are inspected with an off-the-shelf drone with a high definition camera underneath the drone. The results provide a benchmark for comparison. Next, the new approach to bridge inspection by using a 360° camera on top of the drone is tested. The images of the critical parts of the bridge that were taken with the 360° camera on top of the drone are analyzed and compared to the images of the conventional approach with the camera underneath the drone. The results show that a 360° camera can be used for crack and defect detection with similar results to a standard high definition camera. Furthermore, the 360° camera is more suitable for inspecting corners or the ceiling of, e.g., an arch bridge.

The activating receptor natural killer group 2, member D (NKG2D) represents an attractive target for immunotherapy as it exerts a crucial role in cancer immunosurveillance by regulating the activity of cytotoxic lymphocytes. In this study, a panel of novel NKG2D-specific single-chain fragments variable (scFv) were isolated from naïve human antibody gene libraries and fused to the fragment antigen binding (Fab) of rituximab to obtain [CD20×NKG2D] bibodies with the aim to recruit cytotoxic lymphocytes to lymphoma cells. All bispecific antibodies bound both antigens simultaneously. Two bibody constructs, [CD20×NKG2D#3] and [CD20×NKG2D#32], efficiently activated natural killer (NK) cells in co-cultures with CD20+ lymphoma cells. Both bibodies triggered NK cell-mediated lysis of lymphoma cells and especially enhanced antibodydependent cell-mediated cytotoxicity (ADCC) by CD38 or CD19 specific monoclonal antibodies suggesting a synergistic effect between NKG2D and FcgRIIIA signaling pathways in NK cell activation. The [CD20×NKG2D] bibodies were not effective in redirecting CD8+ T cells as single agents, but enhanced cytotoxicity when combined with a bispecific [CD19×CD3] T cell engager, indicating that NKG2D signaling also supports CD3-mediated T cell activation. In conclusion, engagement of NKG2D with bispecific antibodies is attractive to directly activate cytotoxic lymphocytes or to support their activation by monoclonal antibodies or bispecific T cell engagers. As a perspective, cotargeting of two tumor antigens may allow fine-tuning of antibody cancer therapies. Our proposed combinatorial approach is potentially applicable for many existing immunotherapies but further testing in different preclinical models is necessary to explore the full potential. [ABSTRACT FROM AUTHOR]

Recently, the flow state, a state in which individuals perform at the peak of their ability and are completely immersed in the task while experiencing a state of elatedness, has been the subject of active research. We introduce a novel approach of using convolutional neural networks to recognize flow in live performing musicians from analyzing their facial expression. A modified and partially re-trained version of the popular ResNet-50 architecture is employed for binary classification of flow, achieving a detection accuracy of 77.55 percent. This is done on labelled YouTube video-data of musicians with a labeling strategy that was verified through a perception experiment. Maximum accuracy within a 5-fold cross-validation is 74.98 percent with the mean exhibiting an accuracy of 65.10 percent. The results indicate that the state of flow is indeed recognizable through facial expressions of musicians. In addition, the utility of the presented model is demonstrated in two exemplary applications: Predicting the popularity of YouTube videos based on flow recognized in the faces through our system and correlating flow and six discrete emotions (neutral, happy, angry, fear, disgust, surprise). [ABSTRACT FROM AUTHOR]