Design, Manufacturing and Testing of an Environmentally-Green Bipropellant Thruster

This project reviews the design, manufacturing and experimentation process of a green bi-propellant thruster designed to output 5 lbf. The goals were to successfully design, manufacture and test a thruster, while discovering the complications that arise through out the complete design process of a green thruster. The thruster was successfully designed using ideal rocket equations and the design was successfully confirmed using CFD and FEA. Manufacturing of the thruster was fully planned and revealed mild flaws in thruster design. For example some features were not manufacturable to the exact measurements desired. Testing of the engine gave results inconsistent with expected values with a maximum nominal thrust of 2.38 lbf. Measurement errors in thrust and mass flow rates caused calculations of thruster performance, such as ISP, to vary from expected values. Measurement errors are suspected to stem from a combination of incorrect ideal assumptions and test bed design flaws

In Vivo Evaluation of (-)-Zampanolide Demonstrates Potent and Persistent Antitumor Efficacy When Targeted to the Tumor Site.

Microtubule-stabilizing agents (MSAs) are a class of compounds used in the treatment of triple-negative breast cancer (TNBC), a subtype of breast cancer where chemotherapy remains the standard-of-care for patients. Taxanes like paclitaxel and docetaxel have demonstrated efficacy against TNBC in the clinic, however new classes of MSAs need to be identified due to the rise of taxane resistance in patients. (-)-Zampanolide is a covalent microtubule stabilizer that can circumvent taxane resistance in vitro but has not been evaluated for in vivo antitumor efficacy. Here, we determine that (-)-zampanolide has similar potency and efficacy to paclitaxel in TNBC cell lines, but is significantly more persistent due to its covalent binding. We also provide the first reported in vivo antitumor evaluation of (-)-zampanolide where we determine that it has potent and persistent antitumor efficacy when delivered intratumorally. Future work on zampanolide to further evaluate its pharmacophore and determine ways to improve its systemic therapeutic window would make this compound a potential candidate for clinical development through its ability to circumvent taxane-resistance mechanisms

High-precision predictions for the acoustic scale in the non-linear regime

We measure shifts of the acoustic scale due to nonlinear growth and redshift distortions to a high precision using a very large volume of high-force-resolution simulations. We compare results from various sets of simulations that differ in their force, volume, and mass resolution. We find a consistency within 1.5-sigma for shift values from different simulations and derive shift alpha(z) -1 = (0.300\pm 0.015)% [D(z)/D(0)]^{2} using our fiducial set. We find a strong correlation with a non-unity slope between shifts in real space and in redshift space and a weak correlation between the initial redshift and low redshift. Density-field reconstruction not only removes the mean shifts and reduces errors on the mean, but also tightens the correlations: after reconstruction, we recover a slope of near unity for the correlation between the real and redshift space and restore a strong correlation between the low and the initial redshifts. We derive propagators and mode-coupling terms from our N-body simulations and compared with Zeldovich approximation and the shifts measured from the chi^2 fitting, respectively. We interpret the propagator and the mode-coupling term of a nonlinear density field in the context of an average and a dispersion of its complex Fourier coefficients relative to those of the linear density field; from these two terms, we derive a signal-to-noise ratio of the acoustic peak measurement. We attempt to improve our reconstruction method by implementing 2LPT and iterative operations: we obtain little improvement. The Fisher matrix estimates of uncertainty in the acoustic scale is tested using 5000 (Gpc/h)^3 of cosmological PM simulations from Takahashi et al. (2009). (abridged)Comment: Revised to match the version in print: a new figure (figure 6) is added and Section 5 (and figure 8) is revised to include more details. 19 emulated apj pages with 13 figures and 3 table

Re-evaluation of the Fijianolide/Laulimalide Chemotype Suggests an Alternate Mechanism of Action for C-15/C-20 Analogs.

Herein, we report on naturally derived microtubule stabilizers with activity against triple negative breast cancer (TNBC) cell lines, including paclitaxel, fijianolide B/laulimalide (3), fijianolide B di-acetate (4), and two new semisynthetic analogs of 3, which include fijianolide J (5) and fijianolide L (6). Similar to paclitaxel, compound 3 demonstrated classic microtubule stabilizing activity with potent (GI50 = 0.7–17 nM) antiproliferative efficacy among the five molecularly distinct TNBC cell lines. Alternatively, compounds 5 or 6, generated from oxidation of C-20 or C-15 and C-20 respectively, resulted in a unique profile with reduced potency (GI50 = 4–9 μM), but improved efficacy in some lines, suggesting a distinct mechanism of action. The C-15, C-20 di-acetate, and dioxo modifications on 4 and 6 resulted in compounds devoid of classic microtubule stabilizing activity in biochemical assays. While 4 also had no detectable effect on cellular microtubules, 6 promoted a reorganization of the cytoskeleton resulting in an accumulation of microtubules at the cell periphery. Compound 5, with a single C-20 oxo substitution, displayed a mixed phenotype, sharing properties of 3 and 6. These results demonstrate the importance of the C-15/C-20 chiral centers, which appear to be required for the potent microtubule stabilizing activity of this chemotype and that oxidation of these sites promotes unanticipated cytoskeletal alterations that are distinct from classic microtubule stabilization, likely through a distinct mechanism of action

BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.

Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health

Two Factor Reprogramming of Human Neural Stem Cells into Pluripotency

BACKGROUND:Reprogramming human somatic cells to pluripotency represents a valuable resource for the development of in vitro based models for human disease and holds tremendous potential for deriving patient-specific pluripotent stem cells. Recently, mouse neural stem cells (NSCs) have been shown capable of reprogramming into a pluripotent state by forced expression of Oct3/4 and Klf4; however it has been unknown whether this same strategy could apply to human NSCs, which would result in more relevant pluripotent stem cells for modeling human disease. METHODOLOGY AND PRINCIPAL FINDINGS:Here, we show that OCT3/4 and KLF4 are indeed sufficient to induce pluripotency from human NSCs within a two week time frame and are molecularly indistinguishable from human ES cells. Furthermore, human NSC-derived pluripotent stem cells can differentiate into all three germ lineages both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE:We propose that human NSCs represent an attractive source of cells for producing human iPS cells since they only require two factors, obviating the need for c-MYC, for induction into pluripotency. Thus, in vitro human disease models could be generated from iPS cells derived from human NSCs