Teaching Designing for Additive Manufacturing: Formulating Educational Interventions That Encourage Design Creativity.

As additive manufacturing (AM) processes become more ubiquitous in engineering, design, and manufacturing, the need for a workforce skilled in designing for additive manufacturing (DfAM) has grown. Despite this need for an AM-skilled workforce, little research has systematically investigated the formulation of educational interventions for training engineers in DfAM. In this article, we synthesize findings from our experiments with 596 engineering design students to inform the development of educational interventions-comprising content presentations and design tasks-that encourage student learning and creativity. Specifically, we investigated the effects of four variations of DfAM educational interventions by manipulating the following: (1) the content of DfAM information presented, (2) the order of presenting the DfAM content, (3) the definition of the AM design task, and (4) the competitive structure of the AM design task. The effects of these variations were experimentally tested by comparing changes in students' DfAM self-efficacy and the creativity of students' design outcomes. Validated measures were also developed as part of our studies to help mature the nascent field of DfAM education. Based on the findings of our experiments, we discuss how task-based educational interventions can be formulated to (1) increase students' DfAM self-efficacy, (2) encourage students to generate ideas of high AM technical goodness, and (3) encourage students to generate more creative ideas when using AM. The novel synthesis of our findings in this article will help educators formulate effective DfAM educational interventions and tasks to foster a workforce skilled in DfAM.

Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers.

Pancreatic ductal adenocarcinoma (PDA) was responsible for ~ 44,000 deaths in the United States in 2018 and is the epitome of a recalcitrant cancer driven by a pharmacologically intractable oncoprotein, KRAS1-4. Downstream of KRAS, the RAF→MEK→ERK signaling pathway plays a central role in pancreatic carcinogenesis5. However, paradoxically, inhibition of this pathway has provided no clinical benefit to patients with PDA6. Here we show that inhibition of KRAS→RAF→MEK→ERK signaling elicits autophagy, a process of cellular recycling that protects PDA cells from the cytotoxic effects of KRAS pathway inhibition. Mechanistically, inhibition of MEK1/2 leads to activation of the LKB1→AMPK→ULK1 signaling axis, a key regulator of autophagy. Furthermore, combined inhibition of MEK1/2 plus autophagy displays synergistic anti-proliferative effects against PDA cell lines in vitro and promotes regression of xenografted patient-derived PDA tumors in mice. The observed effect of combination trametinib plus chloroquine was not restricted to PDA as other tumors, including patient-derived xenografts (PDX) of NRAS-mutated melanoma and BRAF-mutated colorectal cancer displayed similar responses. Finally, treatment of a patient with PDA with the combination of trametinib plus hydroxychloroquine resulted in a partial, but nonetheless striking disease response. These data suggest that this combination therapy may represent a novel strategy to target RAS-driven cancers.

Publisher Correction: Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers.

In the version of this article initially published, the label over the bottom schematic in Fig. 1a was "pH > 5.0"; it should have been "pH < 5.0". Further, the original article misspelt the surname of Katrin P. Guillen as "Gullien". These errors have been corrected in the print, PDF and HTML versions of the article.