Purpose: We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non-small cell lung cancer (NSCLC) when compared with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival.Experimental Design: To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting (N ¼ 98) and in cell lines (N ¼ 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of L-glutamine (Gln) uptake in lung cancer cell lines in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-L-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines.Results: Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na þ -dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling.Conclusions: These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells' metabolism, growth, and survival.
We describe the design features that underlie the operation of iSprawl, a small (0.3 kg) autonomous, bio-inspired hexapod that runs at 15 body-lengths/second (2.3 m/s). These features include a tuned set of leg compliances for efficient running and a light and flexible power transmission system. This transmission system permits high speed rotary power to be converted to periodic thrusting and distributed to the tips of the rapidly swinging legs. The specific resistance of iSprawl is approximately constant at 1.75 for speeds between 1.25 m/s and 2.5 m/s. Examination of the trajectory of the center of mass and the ground reaction forces for iSprawl show that it achieves a stable, bouncing locomotion similar to that seen in insects and in previous (slower) bio-inspired robots, but with an unusually high stride frequency for its size.
Uni- and triaxial accelerometer outputs have a linear relationship with speed during walking. During running, uniaxial accelerometer outputs plateau because of the biomechanics of running, whereas triaxial accelerometer output has a linear relationship. The combined methodologies predict .VO2 better than either predictor alone; a subject's individually calibrated data further improves .VO2 estimation.
BackgroundOncogenic mechanisms in small-cell lung cancer remain poorly understood leaving this tumor with the worst prognosis among all lung cancers. Unlike other cancer types, sequencing genomic approaches have been of limited success in small-cell lung cancer, i.e., no mutated oncogenes with potential driver characteristics have emerged, as it is the case for activating mutations of epidermal growth factor receptor in non-small-cell lung cancer. Differential gene expression analysis has also produced SCLC signatures with limited application, since they are generally not robust across datasets. Nonetheless, additional genomic approaches are warranted, due to the increasing availability of suitable small-cell lung cancer datasets. Gene co-expression network approaches are a recent and promising avenue, since they have been successful in identifying gene modules that drive phenotypic traits in several biological systems, including other cancer types.ResultsWe derived an SCLC-specific classifier from weighted gene co-expression network analysis (WGCNA) of a lung cancer dataset. The classifier, termed SCLC-specific hub network (SSHN), robustly separates SCLC from other lung cancer types across multiple datasets and multiple platforms, including RNA-seq and shotgun proteomics. The classifier was also conserved in SCLC cell lines. SSHN is enriched for co-expressed signaling network hubs strongly associated with the SCLC phenotype. Twenty of these hubs are actionable kinases with oncogenic potential, among which spleen tyrosine kinase (SYK) exhibits one of the highest overall statistical associations to SCLC. In patient tissue microarrays and cell lines, SCLC can be separated into SYK-positive and -negative. SYK siRNA decreases proliferation rate and increases cell death of SYK-positive SCLC cell lines, suggesting a role for SYK as an oncogenic driver in a subset of SCLC.ConclusionsSCLC treatment has thus far been limited to chemotherapy and radiation. Our WGCNA analysis identifies SYK both as a candidate biomarker to stratify SCLC patients and as a potential therapeutic target. In summary, WGCNA represents an alternative strategy to large scale sequencing for the identification of potential oncogenic drivers, based on a systems view of signaling networks. This strategy is especially useful in cancer types where no actionable mutations have emerged.
A technique for creating devices for ultrathin layer chromatography (UTLC) using an electrospinning method is described. The devices use a nanofibrous stationary phase with fiber diameters that are 400 nm. Separations of mixtures of laser dyes and mixtures of steroidal compounds were performed to illustrate the capabilities of these new UTLC media. The complete analyses were found to require very little development time and require less solvent than typical TLC methods. The efficiency of the separations was substantially improved compared to that determined using commercial phases. The retention properties and efficiency of the technique are discussed as are the effects of mat thickness and mobile phase composition on the chromatographic properties of the devices.
Robots to date lack the robustness and performance of even the simplest animals when operating in unstructured environments. This observation has prompted an interest in biomimetic robots that take design inspiration from biology. However, even biomimetic designs are compromised by the complexity and fragility that result from using traditional engineering materials and manufacturing methods. We argue that biomimetic design must be combined with structures that mimic the way biological structures are composed, with embedded actuators and sensors and spatially-varied materials. This proposition is made possible by a layered-manufacturing technology called shape deposition manufacturing (SDM). We present a family of hexapedal robots whose functional biomimetic design is made possible by SDM's unique capabilities and whose fast (over four body-lengths per second) and robust (traversal over hip-height obstacles) performance begins to compare to that seen in nature. We describe the design and fabrication of the robots and we present the results of experiments that focus on their performance and locomotion dynamics.
Abstract-This paper reviews a template for dynamical climbing originating in biology, explores its stability properties in a numerical model, and presents empirical data from a physical prototype as evidence of the feasibility of adapting the dynamics of the template to robot that runs vertically upward.The recently proposed pendulous climbing model abstracts remarkable similarities in dynamic wall scaling behavior exhibited by radically different animal species. The present paper's first contribution summarizes a numerical study of this model to hypothesize that these animals' apparently wasteful commitments to lateral oscillations may be justified by a significant gain in the dynamical stability and, hence, the robustness of their resulting climbing capability. The paper's second contribution documents the design and offers preliminary empirical data arising from a physical instantiation of this model. Notwithstanding the substantial differences between the proposed bio-inspired template and this physical manifestation, initial data suggest the mechanical climber may be capable of reproducing both the motions and ground reaction forces characteristic of dynamical climbing animals. Even without proper tuning, the robot's steady state trajectories manifest a substantial exchange of kinetic and potential energy, resulting in vertical speeds of 0.30 m/s (0.75 bl/s) and claiming its place as the first bio-inspired dynamical legged climbing platform.
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