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Although toll-like receptor (TLR) agonists hold great promise as immune modulators for reprogramming the suppressive immune landscape in pancreatic ductal adenocarcinoma (PDAC), their use is limited by poor pharmacokinetics (PK) and off-target systemic inflammatory effects. To overcome these challenges as well as to attain drug synergy, we developed a lipid bilayer (LB)-coated mesoporous silica nanoparticle (silicasome) platform for co-delivery of the TLR7/8 agonist 3M-052 with the immunogenic chemotherapeutic agent irinotecan. This was accomplished by incorporating the C18 lipid tail of 3M-052 in the coated LB, also useful for irinotecan remote loading in the porous interior. Not only did the co-formulated carrier improve PK, but it strengthened the irinotecan-induced immunogenic cell death response by 3M-052-mediated dendritic cell activation at the tumor site as well as participating lymph nodes. The accompanying increase in CD8+ T-cell infiltration along with a reduced number of regulatory T-cells was associated with tumor shrinkage and metastasis disappearance in subcutaneous and orthotopic KRAS-mediated pancreatic carcinoma tumor models. Moreover, this therapeutic outcome was accomplished without drug or nanocarrier toxicity. All considered, dual-delivery strategies that combine chemo-immunotherapy with co-formulated TLR agonists or other lipid-soluble immune modulators predict successful intervention in heterogeneous PDAC immune landscapes.

Integration of Hf-based ferroelectric materials into the MOSFET gate stack introduces new physics that potentially enables continued scaling for both CMOS and memory devices. The electrostatic potential amplification effect arises when the device is engineered to depolarize and hence stabilize the ferroelectric negative capacitance state, which eliminates the ferroelectric hysteresis and enhances the gate control. On the other hand, when the ferroelectric layer is thick enough to overcome the depolarization field, non-volatile memory function can be realized through the remnant polarization states. Such systems exhibit process and structural compatibility with CMOS technology and thus are of significant application relevance. Experiments have demonstrated low-voltage operations for both types of devices, showing promising prospects for next-generation logic devices with high reliability.To harness the effects for designing the NCFET and FeFET devices, it is important to understand the behaviours of the ferroelectric layer in the relevant states. In this dissertation, the polarization responses of negative capacitance states are modeled from different aspects through self-consistent device and circuit models that are calibrated to experimental measurements. First, the 101-stage ring oscillator consisting of 14 nm FinFET devices with a ferroelectric gate layer that exhibits negative capacitance are used to study the response speed of the negative capacitance effect. The consistency of the device DC characteristics and the circuit oscillations with less than 10ps per-stage delay confirm the fast negative capacitance response. Next, NCFET device characteristics and scaling trends that are unexpected by conventional theory were explained with non-linear negative capacitance responses as described by the Landau's phenomenology. Design insights are drawn, and the observation bodes well for extending the MOSFET gate length scaling limit. Finally, high-speed NCFET RF operati

Immune tumor microenvironment (TME) in neuroblastoma (NBL) contributes to tumor behavior and treatment response. T cells and natural killer (NK) cells have been shown to play important roles in the neuroblastoma TME. However, few reports address the clinical relevance of natural killer T cells (NKTs) and interleukin-15 (IL-15), one of the crucial cytokines controlling the activation and expansion of NK/NKT cells, in NBL. In this study, we examined NKT immunoscores and IL-15 expression in both MYCN-amplified and MYCN-non-amplified NBL to correlate with clinical outcomes such as event-free survival (EFS) and overall survival (OS). From Gene Expression Omnibus (GEO) datasets GSE45480 (n = 643) and GSE49711 (n = 493), we found that NKT immunoscore and IL-15 expression were both significantly lower in MYCN-amplified NBL, and similar results were observed using our clinical NBL samples (n = 53). Moreover, NBL patients (GEO dataset GSE49711 and our clinical samples) with both lower NKT immunoscore and IL-15 expression exhibited decreased EFS and OS regardless of MYCN gene amplification status. Multivariate analysis further showed that the combination of low NKT immunoscore and low IL-15 expression level was an independent prognostic factor for poor EFS and OS in our NBL patients. These findings provide the rationale for the development of strategy to incorporate IL-15 and NKT cell therapy into the treatment regimen for neuroblastoma.

The side-effect effect (SEE) is the observation that people's intuition about whether an action was intentional depends on whether the outcome is good or bad. The asymmetric response, however, does not represent all subjects' judgments (Nichols and Ulatowski, 2007). It remains unexplored on subjective factors that can mediate the size of SEE. Thus, the current study investigated whether an individual related factor, specifically, whether adults' intensity of caring about an outcome of someone's actions influences their judgments about whether that person intended the outcome. We hypothesized that participants' judgments about fictional agents' responsibility for their action's side-effects would depend on how much they care about the domain of the side-effect. In two experiments, the intensity of caring affected participants' ascription of intention to an agent's negative unintended side-effect. The stronger ascription of intentionality to negative than positive side-effects (i.e., the SEE; Knobe, 2003) was found only in domains in which participants reported higher levels of caring. Also, the intensity of caring increased intentionality attributions reliably for negative side-effects but not for positive side-effects. These results suggest that caring about a domain mediates an asymmetrical ascription of intentionality to negative more than positive side-effects.

Nowadays, consumers actively search for user generated information as substitute for corporation generated information, and the increasing number of user generated online reviews has changed the consumer purchase behaviour in several ways. However, how to precisely predict the influence of user generated online reviews on sales performance might be unclearly understood. Therefore, the aim of this study is to measure the impact of electronic word-of-mouth produced from YouTube movie reviews on consumers’ purchase decisions in terms of three observable variables, the number of viewers, subscribers and reviews. In total, 286 copies of online questionnaire were collected from selected channels on YouTube and virtual communities on Facebook. Briefly, this study has verified the influence of YouTube reviews as a reference point for potential buyers and has understood the relationship between influential power and observable variables.