During this adventure, your only companion is a small robot named ASE. Together you will traverse the moon, explore abandoned facilities, gather clues and ultimately uncover the secrets and hidden agendas of those long gone!
The Beats Fit Pro True Wireless are the sportier sibling of the Beats Studio Buds True Wireless. Unlike the Studio Buds, they're packed with a few more iOS-centric features like an H1 chip for seamless pairing with your Apple devices, adaptive EQ, which is advertised by Apple to optimize sound delivery to the unique shape of your ears, and Spatial Audio support including head tracking. They also have an adaptive active noise cancelling (ANC) system that automatically adapts to the noise around you. Unfortunately, users have reported a buzzing sound coming from their left bud. It's worth noting that we didn't experience this issue, though.
These buds have a mediocre battery performance. They manufacturer advertises them to last six hours continuously, but we measured just over five. Battery life varies depending on use. Luckily, their carrying case supplies an extra three charges. They also have a five-minute quick charge that delivers one hour of playtime when the battery's low, and you can even use one bud while the other is charging. If you value a longer continuous battery life, check out the Sennheiser MOMENTUM True Wireless 3 instead.
Deliver Us The Moon is a Sci-Fi thriller set in an apocalyptic near future where Earth's natural resources are depleted. In an effort to solve the energy crisis, global powers created the World Space Agency and secured a promising new source of energy on the moon.The World Space Agency colonized and operated from the moon until one fateful night all communications with Earth ceased and the energy source was lost. Now, years later, you assume the role of Earth's last astronaut on a do-or-die mission to investigate what happened and save humanity.
In total, there are eight phases: New Moon, Waxing Crescent, First Quarter, Waxing Gibbous, Full Moon, Waning Gibbous, Third Quarter, and Waning Crescent. With default settings, the moon will change each night, but you can change the length of the phases in the Environment section of Game Options. If you want, you can also make a phase permanent or turn off moon effects.
Yes, the moon phase will affect your Sim! Each phase grants a special gameplay boost that can be viewed by hovering over the moon icon at the bottom center of the screen. This information will also display the current phase. Are you curious when the next full moon is coming around? The calendar has also been updated to display upcoming moon phases based on the previously mentioned phase length settings.
Occult Sims will find that the moon now plays an extra role in how their powers behave. During certain moon phases, Mermaids have less hydration loss, Vampires recharge power slower, Spellcasters cast spells more successfully, and Aliens receive a special moodlet while moonbathing (which is also now a thing for all Sims Teen and older)!
In the PanCancer IO 360 analysis, genes and signatures are compared to clinical annotations through heat maps, volcano plots, forest plots, box plots, waterfall plots, swim lane plots, Kaplan Myer plots, scatter plots, and the IO 360 wheel plot. The report is delivered in an HTML format that provides interactive visualizations, quality control, and downloadable results. Data are analyzed individually and as part of larger treatment groups.
Cancer immunotherapies have made a great progress and hold much promise in the treatment of cancer. Specifically, in the case of B-cell malignancies (such as Acute Lymphoblastic Leukemia, or ALL), CAR (chimeric antigen receptor) and TCR (T-cell receptor) therapies have demonstrated encouraging clinical results. As we begin to target solid tumors with TCR and CAR T-cells, the hurdle of being able to select a suitable target and achieve successful cellular delivery/homing to the site of disease remains. With this in mind, being able to visualize a rapidly dividing cellular population is another obstacle to consider.
To address these weaknesses, we developed a novel immunotherapy capable of delivering previously encountered antigenic peptides specifically to cancer cells and facilitating their presentation through the MHC class I pathway. It utilizes a synthetic nanoparticle delivery system comprised of three components: a neutral stealth liposome, encapsulated synthetic immunogenic HLA class I restricted peptides derived from measles virus (MV), and a tumor-targeting peptide on the external surface of the liposome. The targeting peptide results in accumulation of liposomes specifically inside cancer cells, and facilitates presentation of MV-derived immunogenic peptides in HLA class I molecules (Figure 1). We refer to this system as TALL (Targeted Antigen Loaded Liposomes). Therefore, TALL can generate a secondary immune response specifically against the targeted tumor cells in a patient who has been previously vaccinated against or infected by MV. In short, we are attempting to trick the immune system into responding as though the cancer cell is infected with MV without the use of viral particles.
Only a minority of patients with advanced NSCLC truly benefit from single-agent PD-1 checkpoint blockade, and more robust predictive biomarkers are needed to optimally deliver these therapies. The GeoMx Digital Spatial Profiler (DSP) (NanoString, Inc.) allows high-plex protein expression analysis in a quantitative and spatially-resolved manner from single formalin-fixed paraffin embedded tissue sections. Here we use this technology as a discovery tool to find protein markers associated with benefit from single-agent PD-1 checkpoint blockade in NSCLC.
AUTO6NG T-cells (product A/B/A+B) were highly potent in cytotoxicity assays against GD2 positive tumour cell lines with no differences observed compared with single transduced CAR T-cells (product A or B). Expression of the IL7R_CCR in both AUTO6NG and product A conferred exogenous-cytokine-independent viability and homeostatic proliferation of modified T-cells, without causing autonomous T-cell growth. Furthermore, AUOTO6NG T-cells and product B but not product A proved resistant to both TGFb- and PD1/PDL1-mediated immunosuppression in vitro due to the presence of dnTGFbRII and dSHP2 in those genetically engineered CAR T-cells. Finally, intravenous delivery of AUTO6NG exhibited potent anti-tumour activity and extended survival in NSG mice with established tumour burden.
Protein and peptide antigens were delivered to the cytosol of murine splenocytes or human PBMCs by microfluidic squeezing. The response to in vivo immunization was assessed by flow cytometry in a series of experiments in mice. Tumor experiments were conducted with the TC-1 cell line, which expresses the viral antigens E6 and E7 from human papilloma virus type 16 (HPV16).
In mice, we demonstrate that microfluidic squeezing enables delivery to all cell subsets within the spleen and that delivered protein antigen is rapidly processed and presented on MHC-I. In vivo immunization using splenocytes squeezed with a HPV16-derived E7 SLP primes E7-specific responses. Prophylactic immunization of mice implanted with TC-1 resulted in complete protection and these responses were durable, as mice were protected upon TC-1 re-challenge. Therapeutic immunization following TC-1 implantation reduced tumor growth and extended survival compared to unimmunized mice (25 days vs 50 days). Following therapeutic immunization, 85% of tumor infiltrating CD8+ T cells were found to be E7-specific compared to 3% in unimmunized mice.
In human cells, we demonstrate that squeezing of primary PBMCs enables delivery to all cell subsets. Delivery of CMV and HPV16 SLPs leads to presentation on MHC-I, as demonstrated by in vitro responses of both CD8+ T cell clones and patient-derived memory populations. Delivery of CMV antigens at the manufacturing scale (~1 x 10^9 cells) also results in presentation and activation of CD8+ T cells.
Through the direct cytosolic delivery of antigen, we engineered unfractionated PBMCs to function as potent APCs. This strategy has demonstrated significant potential to generate CD8+ T cell responses in both mouse and human systems and has been scaled for clinical implementation.
Current chimeric antigen receptor (CAR) T cell therapies are clinically efficacious against several B cell malignancies, but are less effective at eliminating solid tumors. A key contributor to this observed lack of efficacy is the tumor microenvironment (TME) that is erected by solid tumors to impose immunosuppressive physical and chemical barriers to T cell function and survival. To break TME-driven immunosuppression, attempts have been made to arm CAR-T cells with the ability to produce immunomodulatory payloads that target features of the TME. By their nature, these immunomodulators (e.g. Interleukin 12) are frequently toxic when systemically delivered. Due to a limited repertoire of existing programmable gene regulators, constitutive expression and systemic distribution of immunomodulators by armed CAR-T cells is common.
Methods include: design and characterization of a proprietary bicistronic GoldCAR lentiviral vector to simultaneously deliver both CAR and IL12 transgenes; production of lentivirus and infection of primary human T cells; in vitro characterization of GoldCAR-T cell function utilizing cell based assays, immunoassays and flow cytometry; implantation of subcutaneous xenograft tumors in NSG mice with tumor growth monitored by caliper and bioluminescent imaging (BLI) to assess in vivo efficacy; and ex vivo analysis of blood, tumor and lymphatic organs to characterize safety profile.
CD19 targeted GoldCAR-T cells delivering IL12 demonstrate improved efficacy over standard CD19 CAR-T cells in a subcutaneous Daudi B cell xenograft mouse model. These GoldCAR-T cells exhibit comparable efficacy to CAR-T cells with constitutive IL12 expression, but levels of pro-inflammatory cytokines in the peripheral blood are lower in the mice treated with GoldCAR-T cells. 2b1af7f3a8