Using Inclusive Design to Improve the Accessibility of Informal STEM Education, for Children with Visual Impairment

In this research paper, STEM workshops are designed to provide experiences for twenty-five blind and visually impaired children at a summer camp, with STEM activities that are engaging and fun as well as educational. The aspiration is that the participants should have equitable experiences to their peers without visual impairment, so that they may get the same enjoyment from the STEM workshops as any other participants. Another research goal is to investigate the accessibility features of various commercially available robots, and consider the stability of accessibility features as robots are updated and replaced over time. An analytical autoethnographic approach and an Inclusive Design Model are used, which employ the researcher’s experience as a blind person and children’s feedback to inform ongoing design revisions to the Informal STEM Education activities. Children experimented with playing with and programming robotic toys such as a Bee-bot, Cubetto, Cubelets and Lego Mindstorm EV3, using modified mats and building materials. Video recording, group interviews and direct observation were the data collection tools used. Although all of the STEM education tools used in this study required at least some modification to make them more accessible for the participants, the amount of modification needed varied widely. Some tools were nearly accessible out of the box, while others could not easily be made accessible at all. This suggests many avenues for future research into the accessibility of tools for STEM education, especially robots. The inclusive design of some potential STEM education activities which were not tested, for lack of time, are also described

Diamonds in the Rough: Harnessing Tumor-Associated Myeloid Cells for Cancer Therapy

Therapeutic approaches that engage immune cells to treat cancer are becoming increasingly utilized in the clinics and demonstrated durable clinical benefit in several solid tumor types. Most of the current immunotherapies focus on manipulating T cells, however, the tumor microenvironment (TME) is abundantly infiltrated by a heterogeneous population of tumor-associated myeloid cells, including tumor-associated macrophages (TAMs), tumor-associated dendritic cells (TADCs), tumor-associated neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs). Educated by signals perceived in the TME, these cells often acquire tumor-promoting properties ultimately favoring disease progression. Upon appropriate stimuli, myeloid cells can exhibit cytoxic, phagocytic, and antigen-presenting activities thereby bolstering antitumor immune responses. Thus, depletion, reprogramming or reactivation of myeloid cells to either directly eradicate malignant cells or promote antitumor T-cell responses is an emerging field of interest. In this review, we briefly discuss the tumor-promoting and tumor-suppressive roles of myeloid cells in the TME, and describe potential therapeutic strategies in preclinical and clinical development that aim to target them to further expand the range of current treatment options

Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy.

BACKGROUND: Modulation and depletion strategies of regulatory T cells (Tregs) constitute valid approaches in antitumor immunotherapy but suffer from severe adverse effects due to their lack of selectivity for the tumor-infiltrating (ti-)Treg population, indicating the need for a ti-Treg specific biomarker. METHODS: We employed single-cell RNA-sequencing in a mouse model of non-small cell lung carcinoma (NSCLC) to obtain a comprehensive overview of the tumor-infiltrating T-cell compartment, with a focus on ti-Treg subpopulations. These findings were validated by flow cytometric analysis of both mouse (LLC-OVA, MC38 and B16-OVA) and human (NSCLC and melanoma) tumor samples. We generated two CCR8-specific nanobodies (Nbs) that recognize distinct epitopes on the CCR8 extracellular domain. These Nbs were formulated as tetravalent Nb-Fc fusion proteins for optimal CCR8 binding and blocking, containing either an antibody-dependent cell-mediated cytotoxicity (ADCC)-deficient or an ADCC-prone Fc region. The therapeutic use of these Nb-Fc fusion proteins was evaluated, either as monotherapy or as combination therapy with anti-programmed cell death protein-1 (anti-PD-1), in both the LLC-OVA and MC38 mouse models. RESULTS: We were able to discern two ti-Treg populations, one of which is characterized by the unique expression of Ccr8 in conjunction with Treg activation markers. Ccr8 is also expressed by dysfunctional CD4+ and CD8+ T cells, but the CCR8 protein was only prominent on the highly activated and strongly T-cell suppressive ti-Treg subpopulation of mouse and human tumors, with no major CCR8-positivity found on peripheral Tregs. CCR8 expression resulted from TCR-mediated Treg triggering in an NF-κB-dependent fashion, but was not essential for the recruitment, activation nor suppressive capacity of these cells. While treatment of tumor-bearing mice with a blocking ADCC-deficient Nb-Fc did not influence tumor growth, ADCC-prone Nb-Fc elicited antitumor immunity and reduced tumor growth in synergy with anti-PD-1 therapy. Importantly, ADCC-prone Nb-Fc specifically depleted ti-Tregs in a natural killer (NK) cell-dependent fashion without affecting peripheral Tregs. CONCLUSIONS: Collectively, our findings highlight the efficacy and safety of targeting CCR8 for the depletion of tumor-promoting ti-Tregs in combination with anti-PD-1 therapy

Atomic ordering in Tin-Containing Titannia Gels

Sn-119 and O-17 magic angle spinning NMR spectra of xTiO(2) .(1 - x)SnO2 (x = 0.75, 0.8, 0.85) gels are presented. In these compounds a range of tin environments are observed, consistent with the cations being randomly distributed. In the initial gels, the oxygen environment is already rutile-like and no resonances from pure SnO2 are observed

Unleashing Tumour-Dendritic Cells to Fight Cancer by Tackling Their Three A’s: Abundance, Activation and Antigen-Delivery

Recent advances in cancer immunotherapy have mainly focused on re-activating T-cell responses against cancer cells. However, both priming and activation of effector T-cell responses against cancer-specific antigens require cross-talk with dendritic cells (DCs), which are responsible for the capturing, processing and presentation of tumour-(neo)antigens to T cells. DCs consequently constitute an essential target in efforts to generate therapeutic immunity against cancer. This review will discuss recent research that is unlocking the cancer-fighting potential of tumour-infiltrating DCs. First, the complexity of DCs in the tumour microenvironment regarding the different subsets and the difficulty of translating mouse data into equivalent human data will be briefly touched upon. Mainly, possible solutions to problems currently faced in DC-based cancer treatments will be discussed, including their infiltration into tumours, activation strategies, and antigen delivery methods. In this way, we hope to put together a broad picture of potential synergistic therapies that could be implemented to harness the full capacity of tumour-infiltrating DCs to stimulate anti-tumour immune responses in patients

Importance of heat distribution in modern energy efficient electrical vehicles

Electric vehicles have become increasingly popular in recent years due to general global warming but also due to technological advances, cost reductions, increased battery charging capabilities, etc. In order to achieve the most outstanding possible efficiency of the vehicle, the thermal management system of electric vehicles must be efficient throughout the year. One of the problems is that the temperature distribution in the induction motor is not uniform, so that local overheating can occur. Thermoelectric materials make it possible to convert a temperature gradient into electrical energy. The material properties of the motor impose a temperature limit. This paper will describe the materials used for TEE and their impact on the efficiency of electric vehicles. A thermal model represents the temperature distribution within the induction motor, batteries and the entire vehicle, as well as problems that may occur during operation. Convective heat transfer plays an important role in better performance in battery cell development. In particular, the effect of temperature has a significant impact on the behaviour of the battery during acceleration and regenerative braking events. This paper investigates the temperature distribution inside the battery.Električna vozila poslednjih godina postaju sve popularnija usled opšteg globalnog zagrevanja, ali i usled napretka tehnologije, smanjenja troškova, povećavanja mogućnosti punjenja baterija itd. Za postizanje što veće efikasnosti vozila potrebno je da sistem termičkog upravljanja električnim vozilima bude efikasan tokom cele godine. Jedan od problema je da raspodela temperature u pogonskom motoru nije ravnomerna pa može doći do lokalnog pregrevanja. Termoelektrični materijali omogućavaju pretvaranje temperaturnog gradijenta u električnu energiju. Svojstva materijala motora nameću temperaturnu granicu. U ovom radu biće opisani materijali koje se koriste za termoelektrične elemente i njihov uticaj na efikasnost električnih vozila. Termalni model se koristi da bi se predstavila distribuciju temperature unutar indukcionog motora, baterija i celog vozila, kao i problemi koji se mogu javiti tokom rada. Konvektivni prenos toplote ima važnu ulogu za što bolje performanse u razvoju baterijske ćelije. Posebno, raspodela toplote ima značajan uticaj na ponašanje baterije tokom događaja ubrzanja i regenerativnog kočenja. U ovom radu se istražuje i analizira distribucija temperature unutar baterije

Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy.

BACKGROUND: Modulation and depletion strategies of regulatory T cells (Tregs) constitute valid approaches in antitumor immunotherapy but suffer from severe adverse effects due to their lack of selectivity for the tumor-infiltrating (ti-)Treg population, indicating the need for a ti-Treg specific biomarker. METHODS: We employed single-cell RNA-sequencing in a mouse model of non-small cell lung carcinoma (NSCLC) to obtain a comprehensive overview of the tumor-infiltrating T-cell compartment, with a focus on ti-Treg subpopulations. These findings were validated by flow cytometric analysis of both mouse (LLC-OVA, MC38 and B16-OVA) and human (NSCLC and melanoma) tumor samples. We generated two CCR8-specific nanobodies (Nbs) that recognize distinct epitopes on the CCR8 extracellular domain. These Nbs were formulated as tetravalent Nb-Fc fusion proteins for optimal CCR8 binding and blocking, containing either an antibody-dependent cell-mediated cytotoxicity (ADCC)-deficient or an ADCC-prone Fc region. The therapeutic use of these Nb-Fc fusion proteins was evaluated, either as monotherapy or as combination therapy with anti-programmed cell death protein-1 (anti-PD-1), in both the LLC-OVA and MC38 mouse models. RESULTS: We were able to discern two ti-Treg populations, one of which is characterized by the unique expression of Ccr8 in conjunction with Treg activation markers. Ccr8 is also expressed by dysfunctional CD4+ and CD8+ T cells, but the CCR8 protein was only prominent on the highly activated and strongly T-cell suppressive ti-Treg subpopulation of mouse and human tumors, with no major CCR8-positivity found on peripheral Tregs. CCR8 expression resulted from TCR-mediated Treg triggering in an NF-κB-dependent fashion, but was not essential for the recruitment, activation nor suppressive capacity of these cells. While treatment of tumor-bearing mice with a blocking ADCC-deficient Nb-Fc did not influence tumor growth, ADCC-prone Nb-Fc elicited antitumor immunity and reduced tumor growth in synergy with anti-PD-1 therapy. Importantly, ADCC-prone Nb-Fc specifically depleted ti-Tregs in a natural killer (NK) cell-dependent fashion without affecting peripheral Tregs. CONCLUSIONS: Collectively, our findings highlight the efficacy and safety of targeting CCR8 for the depletion of tumor-promoting ti-Tregs in combination with anti-PD-1 therapy

Stromal-targeting radioimmunotherapy mitigates the progression of therapy-resistant tumors

Radioimmunotherapy (RIT) aims to deliver a high radiation dose to cancer cells, while minimizing the exposure of normal cells. Typically, monoclonal antibodies are used to target the radionuclides to cancer cell surface antigens. However, antibodies face limitations due to their poor tumor penetration and suboptimal pharmacokinetics, while the expression of their target on the cancer cell surface may be gradually lost. In addition, most antigens are expressed in a limited number of tumor types. To circumvent these problems, we developed a Nanobody (Nb)-based RIT against a prominent stromal cell (stromal-targeting radioimmunotherapy or STRIT) present in nearly all tumors, the tumor-associated macrophage (TAM). Macrophage Mannose Receptor (MMR) functions as a stable molecular target on TAM residing in hypoxic areas, further allowing the delivery of a high radiation dose to the more radioresistant hypoxic tumor regions. Since MMR expression is not restricted to TAM, we first optimized a strategy to block extra-tumoral MMR to prevent therapy-induced toxicity. A 100-fold molar excess of unlabeled bivalent Nb largely blocks extra-tumoral binding of Lu-177-labeled anti-MMR Nb and prevents toxicity, while still allowing the intra-tumoral binding of the monovalent Nb. Interestingly, three doses of Lu-177-labeled anti-MMR Nb resulted in a significantly retarded tumor growth, thereby outcompeting the effects of antiPD1, anti-VEGFR2, doxorubicin and paclitaxel in the TS/A mammary carcinoma model. Together, these data propose anti-MMR STRIT as a valid new approach for cancer treatment