Serum profiling and biomarker discovery of rat mammary tumors using mass-coded abundance tags (MCAT)

Advances in Mass-spectrometry techniques allow for the rapid processing and evaluation of complex biological mixtures such as blood/serum. These samples represent a protein rich environment as well as a sentinel monitoring system of the entire organism. The central tenet of these studies is that changes in the microenvironment of a tissue, brought about by a disease process, will lead to sufficient changes in the protein and peptide pattern of the serum, such that the differences can be accurately detected and correctly associated with a particular disease state. Using mass-spectrometry approaches we have developed techniques that allow us to compare samples from tumor-free and tumor present serum samples simultaneously to find biomarkers that indicate the presence of cancer. To examine potentially important but less abundant proteins, ultrafiltration (UF) was used to eliminate the more abundant proteins and combine this with the non-isotopic peptide tags (S-methylthioacetimidate and S-methyl thiopropionimidate) described by Beardsley and Reilley (J. Proteome Res. 2: 15-21, 2003) to differentiate our samples. Use of these mass-coded abundance tags (MCAT) allows for simultaneous evaluation of serum samples from tumor present, and tumor free animals. Using an oa time-of-flight mass-spectrometer (Q-tof) with electrospray ionization we produce high quality spectrums to screen for peptides that have only one tag. Specificity of tagging increases the likelihood that the peptide resulted from a protein unique to either the control or conditioned state. Using the ms/ms function of the Q-tof we sequence the peptide and identify the parent protein. Specifically, our lab is using UF, MCAT and the Q-tof to evaluate rat models of chemically-induced tumors. By using animal models we overcome much of the variability that may exist in human serum samples due to differences in gender, diet and cancer initiation. We have shown that these systems allow for the identification of both small molecules such as Alpha S1 casein precursor (24 kDa) as well as proteins greater than the MCO such as Fibrinogen alpha/alpha E precursor and Coagulation factor 2 (86 and 70 kDa, respectively). With positive sequence identification we can now evaluate the tumors themselves to determine if the proteins are over-expressed in the tumor vs. normal tissues. Using this method of “bottom-up” analysis provides information on the nature and composition of our samples to more rapidly identify those proteins that are unique to the tumor state of the animals

Development of a Simulation Framework for CubeSat Performance Modeling

Space systems are notoriously difficult to develop due to the nature of the environment in which they must operate. Designers have only a limited window to ensure systems will function as intended, placing a high importance on testing. This paper discussed the ongoing development of a simulation framework to support Hardware-in-the-Loop (HIL) testing of CubeSat subsystem hardware. This work is being conducted at the Air Force Institute of Technology (AFIT) in support of the institution’s CubeSat program. The simulation framework is organized into the classic spacecraft subsystems. Each of these subsystems will support a software model and interfaces for the integration of flight hardware into the simulation framework. In demonstration of this concept, propulsion hardware has been successfully integrated into the model environment. Telemetry reception and command transmission within the simulation framework is functional and demonstrated. A loop containing the propulsion hardware, simple controller, and orbital motion propagator was developed to demonstrate the HIL test functionality of the simulation framework. This focus on the development of the propulsion HIL test configuration is a point of distinction from other HIL simulations, which typically focus on the Attitude Determination and Control System (ADCS). Presented results validate successful integration of propulsion subsystem hardware into the simulation framework. Future work will focus on the integration of CubeSat subsystem models into the framework

Structural Analysis of Test Flight Vehicles with Multifunctional Energy Storage

Under the NASA Aeronautics Research Mission Directorate (ARMD) Convergent Aeronautical Solutions (CAS) project, NASA Glenn Research Center has been leading Multifunctional Structures for High Energy Lightweight Load-bearing Storage (M-SHELLS) research efforts. The technology of integrating load-carrying structures with electrical energy storage capacity has the potential to reduce the overall weight of future electric aircraft. The proposed project goals were to develop M-SHELLS in the form of honeycomb coupons and subcomponents, integrate them into the structure, and conduct low-risk flight tests onboard a remotely piloted small aircraft. Experimental M-SHELLS energy-storing coupons were fabricated and tested in the laboratory for their electrical and mechanical properties. In this paper, finite element model development and structural analyses of two small test aircraft candidates are presented. The finite element analysis of the initial two-spar wing is described for strain, deflection, and weight estimation. After a test aircraft Tempest was acquired, a load- deflection test of the wing was conducted. A finite element model of the Tempest was then developed based on the test aircraft dimensions and construction detail. The component weight analysis from the finite element model and test measurements were correlated. Structural analysis results with multifunctional energy storage panels in the fuselage of the test vehicle are presented. Although the flight test was cancelled because of programmatic reasons and time constraints, the structural analysis results indicate that the mid-fuselage floor composite panel could provide structural integrity with minimal weight penalty while supplying electrical energy. To explore potential future applications of the multifunctional structure, analyses of the NASA X-57 Maxwell electric aircraft and a NASA N+3 Technology Conventional Configuration (N3CC) fuselage are presented. Secondary aluminum structure in the fuselage sub-floor and cargo area were partially replaced with reinforced five-layer composite panels with M-SHELLS honeycomb core. The N3CC fuselage weight reduction associated with each design without risking structural integrity are described. The structural analysis and weight estimation with the application of composite M-SHELLS panels to the N3CC fuselage indicate a 3.2% reduction in the fuselage structural weight, prior to accounting for the additional weight of core material required to complete the energy storage functionality

Low prevalence of fibrosis in thalassemia major assessed by late gadolinium enhancement cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Heart failure remains a major cause of mortality in thalassaemia major. The possible role of cardiac fibrosis in thalassemia major in the genesis of heart failure is not clear. It is also unclear whether cardiac fibrosis might arise as a result of heart failure.</p> <p>Methods</p> <p>We studied 45 patients with thalassaemia major who had a wide range of current cardiac iron loading and included patients with prior and current heart failure. Myocardial iron was measured using T2* cardiovascular magnetic resonance (CMR), and following this, late gadolinium enhancement (LGE) was used to determine the presence of macroscopic myocardial fibrosis.</p> <p>Results</p> <p>The median myocardial T2* in all patients was 22.6 ms (range 5.3-58.8 ms). Fibrosis was detected in only one patient, whose myocardial T2* was 20.1 ms and left ventricular ejection fraction 57%. No fibrosis was identified in 5 patients with a history of heart failure with full recovery, in 3 patients with current left ventricular dysfunction undergoing treatment, or in 18 patients with myocardial iron loading with cardiacT2* < 20 ms at the time of scan.</p> <p>Conclusion</p> <p>This study shows that macroscopic myocardial fibrosis is uncommon in thalassemia major across a broad spectrum of myocardial iron loading. Importantly, there was no macroscopic fibrosis in patients with current or prior heart failure, or in patients with myocardial iron loading without heart failure. Therefore if myocardial fibrosis indeed contributes to myocardial dysfunction in thalassemia, our data combined with the knowledge that the myocardial dysfunction of iron overload can be reversed, indicates that any such fibrosis would need to be both microscopic and reversible.</p

Method of manufacturing a light emitting, photovoltaic or other electronic apparatus and system

The present invention provides a method of manufacturing an electronic apparatus, such as a lighting device having light emitting diodes (LEDs) or a power generating device having photovoltaic diodes. The exemplary method includes depositing a first conductive medium within a plurality of channels of a base to form a plurality of first conductors; depositing within the plurality of channels a plurality of semiconductor substrate particles suspended in a carrier medium; forming an ohmic contact between each semiconductor substrate particle and a first conductor; converting the semiconductor substrate particles into a plurality of semiconductor diodes; depositing a second conductive medium to form a plurality of second conductors coupled to the plurality of semiconductor diodes; and depositing or attaching a plurality of lenses suspended in a first polymer over the plurality of diodes. In various embodiments, the depositing, forming, coupling and converting steps are performed by or through a printing process

A 700 year record of Southern Hemisphere extratropical climate variability

Annually dated ice cores from West and East Antarctica provide proxies for past changes in atmospheric circulation over Antarctica and portions of the Southern Ocean, temperature in coastal West and East Antarctica, and the frequency of South Polar penetration of El Niño events. During the period AD 1700–1850, atmospheric circulation over the Antarctic and at least portions of the Southern Hemisphere underwent a mode switch departing from the out-of-phase alternation of multi-decadal long phases of EOF1 and EOF2 modes of the 850 hPa field over the Southern Hemisphere (as defined in the recent record by Thompson and Wallace, 2000; Thompson and Solomon, 2002) that characterizes the remainder of the 700 year long record. From AD 1700 to 1850, lower-tropospheric circulation was replaced by in-phase behavior of the Amundsen Sea Low component of EOF2 and the East Antarctic High component of EOF1. During the first phase of the mode switch, both West and East Antarctic temperatures declined, potentially in response to the increased extent of sea ice surrounding both regions. At the end of the mode switch, West Antarctic coastal temperatures rose and East Antarctic coastal temperatures fell, respectively, to their second highest and lowest of the record. Polar penetration of El Niño events increased during the mode switch. The onset of the AD 1700–1850 mode switch coincides with the extreme state of the Maunder Minimum in solar variability. Late 20th-century West Antarctic coastal temperatures are the highest in the record period, and East Antarctic coastal temperatures close to the lowest. Since AD 1700, extratropical regions of the Southern Hemisphere have experienced significant climate variability coincident with changes in both solar variability and greenhouse gase

Light Emitting, Photovoltaic or Other Electronic Apparatus and System

The present invention provides an electronic apparatus, such as a lighting device comprised of light emitting diodes (LEDs) or a power generating apparatus comprising photovoltaic diodes, which may be created through a printing process, using a semiconductor or other substrate particle ink or suspension and using a lens particle ink or suspension. An exemplary apparatus comprises a base; at least one first conductor; a plurality of diodes coupled to the at least one first conductor; at least one second conductor coupled to the plurality of diodes; and a plurality of lenses suspended in a polymer deposited or attached over the diodes. The lenses and the suspending polymer have different indices of refraction. In some embodiments, the lenses and diodes are substantially spherical, and have a ratio of mean diameters or lengths between about 10:1 and 2:1. The diodes may be LEDs or photovoltaic diodes, and in some embodiments, have a junction formed at least partially as a hemispherical shell or cap

He II Reverberation in Active Galactic Nucleus Spectra

This paper compares the observed reverberation response lags and the intensity ratios of the broad-line region (BLR) emission lines He II λ1640, He II λ4686, and C IV λ1549 with predictions. Published observations indicate that the He II λ1640 lag is 3 times shorter than the lags of He II λ4686 or C IV λ1549. Diverse models, however, do not reproduce this observation. Extensive improved numerical simulations of the hydrogenic isoelectronic sequence emission show that the He II spectrum remains especially simple, even in the central regions of a luminous quasar. Line trapping never builds up a significant population of excited states, and the emissivities of the two He II lines are close to simple case B predictions. Using improved He II calculations, we computed the lags of distributions of clouds concentrated in approximate radius-dependent pressure laws as well as the lags of locally optimally emitting cloud (LOC) distributions. In addition, the effect on lags and intensities due to anisotropic beaming of line emission and observer orientation angle with respect to an obscuring disk is estimated. Comparing our results to observations, we do not see how any distribution of clouds can produce intrinsic He II λ1640 and He II λ4686 emission with substantially different responses, nor do we see how He II λ1640 can vary on a substantially shorter timescale than C IV λ1549. Our models suggest that in fact the observed He II λ1640 reverberation timescale is shorter than expected rather than the observed He II λ4686 timescale being longer than expected. We discuss a possible explanation

Insulin Treatment Attenuates Small Nerve Fiber Damage in Rat Model of Type 2 Diabetes

Introduction. Current clinical guidelines for management of diabetic peripheral neuropathy (DPN) emphasize good glycemic control. However, this has limited effect on prevention of DPN in type 2 diabetic (T2D) patients. This study investigates the effect of insulin treatment on development of DPN in a rat model of T2D to assess the underlying causes leading to DPN. Methods. Twelve-week-old male Sprague-Dawley rats were allocated to a normal chow diet or a 45% kcal high-fat diet. After eight weeks, the high-fat fed animals received a mild dose of streptozotocin to induce hyperglycemia. Four weeks after diabetes induction, the diabetic animals were allocated into three treatment groups receiving either no insulin or insulin-releasing implants in a high or low dose. During the 12-week treatment period, blood glucose and body weight were monitored weekly, whereas Hargreaves’ test was performed four, eight, and 12 weeks after treatment initiation. At study termination, several blood parameters, body composition, and neuropathy endpoints were assessed. Results. Insulin treatment lowered blood glucose in a dose-dependent manner. In addition, both doses of insulin lowered lipids and increased body fat percentage. High-dose insulin treatment attenuated small nerve fiber damage assessed by Hargreaves’ test and intraepidermal nerve fiber density compared to untreated diabetes and low-dose insulin; however, neuropathy was not completely prevented by tight glycemic control. Linear regression analysis revealed that glycemic status, circulating lipids, and sciatic nerve sorbitol level were all negatively associated with the small nerve fiber damage observed. Conclusion. In summary, our data suggest that high-dose insulin treatment attenuates small nerve fiber damage. Furthermore, data also indicate that both poor glycemic control and dyslipidemia are associated with disease progression. Consequently, this rat model of T2D seems to fit well with progression of DPN in humans and could be a relevant preclinical model to use in relation to research investigating treatment opportunities for DPN