The Effect of Incorporating End-User Customization into Additive Manufacturing Designs

In the realm of additive manufacturing there is an increasing trend among makers to create designs that allow for end-users to alter them prior to printing an artifact. Online design repositories have tools that facilitate the creation of such artifacts. There are currently no rules for how to create a good customizable design or a way to measure the degree of customization within a design. This work defines three types of customizations found in additive manufacturing and presents three metrics to measure the degree of customization within designs based on the three types of customization. The goal of this work is to ultimately provide a consistent basis for which a customizable design can be evaluated in order to assist makers in the creation of new customizable designs that can better serve end-user. The types of customization were defined by doing a search of Thingiverse’s online data base of customizable designs and evaluating commonalities between designs. The three types of customization defined by this work are surface, structure, and personal customization. The associated metrics are used to quantify the adjustability of a set of online designs which are then plot against the daily use rate and each other on separate graphs. The use rate data used in this study is naturally biased towards hobbyists due to where the designs used to create the data resides. A preliminary analysis is done on the metrics to evaluate their correlation with design use rate as well as the dependency of the metrics in relation to each other. The trends between the metrics are examined for an idea of how best to provide customizable designs. This work provides a basis for measuring the degree of customization within additive manufacturing design and provides an initial framework for evaluating the usability of designs based on the measured degree of customization relative to the three types of defined customizations

Accountability in Intervention Research: Developing a Fidelity Checklist of a Mental Health Intervention in Prisons

Adherence to intervention content and delivery protocols is vital in establishing the efficacy of treatment programs for mental illnesses. Using a fidelity tool during interventions can substantially increase the likelihood of clients receiving the most scientifically rigorous treatment. This article outlines the steps taken to develop a fidelity checklist to measure treatment adherence of a two-part intervention delivered in a prison setting. Researchers followed the five-step guide by Feely et al. (Child and Adolescent Social Work Journal, 35(2), 139–152: 2018) and describe the process of developing a fidelity tool to measure treatment adherence to a newly adapted CBT-based intervention designed to maximize uptake for participants with serious mental illnesses. Key decision points are discussed, along with final decisions and contextual considerations. A 26-item checklist was developed to measure treatment adherence related to process, content, and adaptations of the intervention. The checklist follows the structure of the CBT intervention, as well as provides flexibility for the delivery adaptations. Pilot testing of the checklist revealed all sessions were implemented with at least 85% fidelity, and 90% of sessions were implemented with at least 90% fidelity. Raters agreed on the fidelity of a session in 99.6% of sessions. Contextual considerations included the highly secure study setting, reconciling the constant monitoring of a group and creating a treatment environment, the flexibility mandated by the intervention, the relative newness of the intervention, and the limitations based on study aims and resources. These results illustrate how study specific considerations and challenges can be successfully navigated in the development and deployment of a fidelity tool in a real-world setting. The fidelity checklist achieved our goal of measuring treatment adherence for this intervention. In the development of a fidelity tool, we recommend leaving space for raters to note specific considerations that disrupt facilitators’ ability to deploy the intervention precisely. Measuring fidelity is imperative for mental health interventions to ensure that the treatment is responsible for the changes observed in clients

Multicomponent kinematics in a massive filamentary IRDC

To probe the initial conditions for high-mass star and cluster formation, we investigate the properties of dense filaments within the infrared dark cloud G035.39-00.33 (IRDC G035.39) in a combined Very Large Array (VLA) and the Green Bank Telescope (GBT) mosaic tracing the NH3 (1,1) and (2,2) emission down to 0.08 pc scales. Using agglomerative hierarchical clustering on multiple line-of-sight velocity component fitting results, we identify seven extended velocity-coherent components in our data, likely representing spatially coherent physical structures, some exhibiting complex gas motions. The velocity gradient magnitude distribution peaks at its mode of 0.35 km/s/pc and has a long tail extending into higher values of 1.5 - 2 km/s/pc, and is generally consistent with those found toward the same cloud in other molecular tracers and with the values found towards nearby low-mass dense cloud cores at the same scales. Contrary to observational and theoretical expectations, we find the non-thermal ammonia line widths to be systematically narrower (by about 20%) than those of N2H+ (1-0) line transition observed with similar resolution. If the observed ordered velocity gradients represent the core envelope solid-body rotation, we estimate the specific angular momentum to be about 2 x 10^21 cm^2/s, similar to the low-mass star-forming cores. Together with the previous finding of subsonic motions in G035.39, our results demonstrate high levels of similarity between kinematics of a high-mass star-forming IRDC and the low-mass star formation regime.Comment: 22 pages, 14 figures, accepted to Ap

Characterizing unknown systematics in large scale structure surveys

Photometric large scale structure (LSS) surveys probe the largest volumes in the Universe, but are inevitably limited by systematic uncertainties. Imperfect photometric calibration leads to biases in our measurements of the density fields of LSS tracers such as galaxies and quasars, and as a result in cosmological parameter estimation. Earlier studies have proposed using cross-correlations between different redshift slices or cross-correlations between different surveys to reduce the effects of such systematics. In this paper we develop a method to characterize unknown systematics. We demonstrate that while we do not have sufficient information to correct for unknown systematics in the data, we can obtain an estimate of their magnitude. We define a parameter to estimate contamination from unknown systematics using cross-correlations between different redshift slices and propose discarding bins in the angular power spectrum that lie outside a certain contamination tolerance level. We show that this method improves estimates of the bias using simulated data and further apply it to photometric luminous red galaxies in the Sloan Digital Sky Survey as a case study.Comment: 24 pages, 6 figures; Expanded discussion of results, added figure 2; Version to be published in JCA

JWST reveals widespread CO ice and gas absorption in the Galactic Center cloud G0.253+0.016

We report JWST NIRCam observations of G0.253+0.016, the molecular cloud in the Central Molecular Zone known as The Brick, with the F182M, F187N, F212N, F410M, F405N, and F466N filters. We catalog 56,146 stars detected in all 6 filters using the crowdsource package. Stars within and behind The Brick exhibit prodigious absorption in the F466N filter that is produced by a combination of CO ice and gas. In support of this conclusion, and as a general resource, we present models of CO gas and ice and CO$_2$ ice in the F466N, F470N, and F410M filters. Both CO gas and ice may contribute to the observed stellar colors. We show, however, that CO gas does not absorb the Pf$\beta$ and Hu$\epsilon$ lines in F466N, but that these lines show excess absorption, indicating that CO ice is also present and contributes to observed F466N absorption. The most strongly absorbed stars in F466N are extincted by $\sim$ 2 magnitudes, corresponding to $>$ 80\% flux loss. This high observed absorption requires very high column densities of CO, requiring total CO column that is in tension with standard CO abundance and/or gas-to-dust ratios. There is therefore likely to be a greater CO/H$_2$ ratio (X$_{CO} > 10^{-4}$) and more dust per H$_2$ molecule ($>0.01$) in the Galactic Center than the Galactic disk. Ice and/or gas absorption is observed even in the cloud outskirts, implying that additional caution is needed when interpreting stellar photometry in filters that overlap with ice bands throughout our Galactic Center. The widespread CO absorption in our Galactic Center hints that significant ice absorption is likely present in other galactic centers.Comment: Submitted to ApJ. Revised after second referee report. 16 pages, 11 figure

MOMENTUM: Microbial Optimization via Metabolic Network Minimization

We report a high-throughput metabolic engineering platform enabling the rapid optimization of microbial production strains. The platform, which bridges a gap between current in vivo and in vitro bio-production approaches, relies on dynamic minimization of the active metabolic network and is implemented in the context of standardized 2-stage bio-processes. Dynamic metabolic network minimization is accomplished using combinations of CRISPR interference and controlled proteolysis to reduce the activity of multiple enzymes in essential central metabolism. This approach not only results in a design space with greatly reduced complexity, but also in increased metabolic fluxes and production rates as well as in strains which are robust to environmental conditions. Robustness leads to predictable scalability from high-throughput µL-scale screens, to fully instrumented L-scale bioreactors. Predictive high-throughput approaches are critical for metabolic engineering programs to truly take advantage of the rapidly increasing throughput and decreasing costs of synthetic biology. We have not only demonstrated proof of principle for this approach in two common industrial microbes: E. coli and S. cerevisiae, but also have validated this approach with the rapid optimization of E. coli strains producing two important industrial chemicals: alanine and mevalonic acid, at commercially meaningful rates, titers (147 g/L and 97 g/L, respectively), and yields.1 References: Ye, Z., Burg, J.M., Poplyk, M.R., Moreb, E.A., Trahan, A.D., Rodrigiuez, D.L., Sheikh, W., Kelly, G.M., Luo, M.L., Beisel C.L., and Lynch, M.D. (2017) MOMENTuM: Microbial Optimization via MEtabolic NeTwork Minimization., Nature Biotechnology in review

A novel HLA-B18 restricted CD8+ T cell epitope is efficiently cross-presented by dendritic cells from soluble tumor antigen

NY-ESO-1 has been a major target of many immunotherapy trials because it is expressed by various cancers and is highly immunogenic. In this study, we have identified a novel HLA-B*1801-restricted CD8<sup>+</sup>T cell epitope, NY-ESO-1<sub>88–96</sub> (LEFYLAMPF) and compared its direct- and cross-presentation to that of the reported NY-ESO-1<sub>157–165</sub> epitope restricted to HLA-A*0201. Although both epitopes were readily cross-presented by DCs exposed to various forms of full-length NY-ESO-1 antigen, remarkably NY-ESO-1<sub>88–96</sub> is much more efficiently cross-presented from the soluble form, than NY-ESO-1<sub>157–165</sub>. On the other hand, NY-ESO-1<sub>157–165</sub> is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A<sub>26–35</sub>; whereas NY-ESO-1<sub>88–96</sub> was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome. It was only presented when the tumor cells were first IFN-γ treated, followed by infection with recombinant vaccinia virus encoding NY-ESO-1, which dramatically increased NY-ESO-1 expression. These data indicate that the presentation of NY-ESO-1<sub>88–96</sub> is immunoproteasome dependent. Furthermore, a survey was conducted on multiple samples collected from HLA-B18+ melanoma patients. Surprisingly, all the detectable responses to NY-ESO-1<sub>88–96</sub> from patients, including those who received NY-ESO-1 ISCOMATRIX™ vaccine were induced spontaneously. Taken together, these results imply that some epitopes can be inefficiently presented by tumor cells although the corresponding CD8<sup>+</sup>T cell responses are efficiently primed in vivo by DCs cross-presenting these epitopes. The potential implications for cancer vaccine strategies are further discussed

Function of specialized regulatory proteins and signaling pathways in exercise-induced muscle mitochondrial biogenesis

AbstractSkeletal muscle mitochondrial content and function are regulated by a number of specialized molecular pathways that remain to be fully defined. Although a number of proteins have been identified to be important for the maintenance of mitochondria in quiescent muscle, the requirement for these appears to decrease with the activation of multiple overlapping signaling events that are triggered by exercise. This makes exercise a valuable therapeutic tool for the treatment of mitochondrially based metabolic disorders. In this review, we summarize some of the traditional and more recently appreciated pathways that are involved in mitochondrial biogenesis in muscle, particularly during exercise

Synthesis and characterisation of halide, separated ion pair, and hydride cyclopentadienyl iron bis(diphenylphosphino)ethane derivatives

Treatment of anhydrous FeX₂ (X = Cl, Br, I) with one equivalent of bis(diphenylphosphino)ethane (dppe) in refluxing THF afforded analytically pure white (X = Cl), light green (X = Br), and yellow (X = I) [FeX₂(dppe)]n (X = Cl, I; Br, II; I, III). Complexes I–III are excellent synthons from which to prepare a range of cyclopentadienyl derivatives. Specifically, treatment of I–III with alkali metal salts of C₅H₅ (Cp, series 1), C₅Me₅ (Cp*, series 2), C₅H₄SiMe₃ (Cp′, series 3), C₅H₃(SiMe₃)₂ (Cp′′, series 4), and C₅H₃(But)₂ (Cptt, series 5) afforded [Fe(Cp†)(Cl)(dppe)] 1Cl–5Cl, [Fe(Cp†)(Br)(dppe)] 1Br–5Br, and [Fe(Cp†)(I)(dppe)] 1I–5I (Cp† = Cp, Cp*, Cp′, Cp′′, or Cptt). Dissolution of 1I–5I in acetonitrile, or treatment of 1Cl–5Cl with Me₃SiI in acetonitrile (no halide exchange reactions were observed in other solvents) afforded the separated ion pair complexes [Fe(Cp†)(NCMe)(dppe)][I] 1SIP–5SIP. Attempts to reduce 1Cl–5Cl, 1Br–5Br, and 1I–5I with a variety of reductants (Li-Cs, KC₈, Na/Hg) were unsuccessful. Treatment of 1Cl–5Cl with LiAlH₄ gave the hydride derivatives [Fe(Cp†)(H)(dppe)] 1H–5H. This report provides a systematic account of reliable methods of preparing these complexes which may find utility in molecular wire and metal–metal bond chemistries. The complexes reported herein have been characterised by X-ray diffraction, NMR, IR, UV/Vis, and Mössbauer spectroscopies, cyclic voltammetry, density functional theory calculations, and elemental analyses, which have enabled us to elucidate the electronic structure of the complexes and probe the variation of iron redox properties as a function of varying the cyclopentadienyl or halide ligand