Identification of integrin drug targets for 17 solid tumor types.

Integrins are contributors to remodeling of the extracellular matrix and cell migration. Integrins participate in the assembly of the actin cytoskeleton, regulate growth factor signaling pathways, cell proliferation, and control cell motility. In solid tumors, integrins are involved in promoting metastasis to distant sites, and angiogenesis. Integrins are a key target in cancer therapy and imaging. Integrin antagonists have proven successful in halting invasion and migration of tumors. Overexpressed integrins are prime anti-cancer drug targets. To streamline the development of specific integrin cancer therapeutics, we curated data to predict which integrin heterodimers are pausible therapeutic targets against 17 different solid tumors. Computational analysis of The Cancer Genome Atlas (TCGA) gene expression data revealed a set of integrin targets that are differentially expressed in tumors. Filtered by FPKM (Fragments Per Kilobase of transcript per Million mapped reads) expression level, overexpressed subunits were paired into heterodimeric protein targets. By comparing the RNA-seq differential expression results with immunohistochemistry (IHC) data, overexpressed integrin subunits were validated. Biologics and small molecule drug compounds against these identified overexpressed subunits and heterodimeric receptors are potential therapeutics against these cancers. In addition, high-affinity and high-specificity ligands against these integrins can serve as efficient vehicles for delivery of cancer drugs, nanotherapeutics, or imaging probes against cancer

The Magellanic Stream: break up and accretion onto the hot Galactic corona

The Magellanic HI Stream (~2x10^9 Msun [d/55 kpc]^2) encircling the Galaxy at a distance 'd' is arguably the most important tracer of what happens to gas accreting onto a disk galaxy. Recent observations reveal that the Stream's mass is in fact dominated (3:1) by its ionised component. Here we revisit the origin of the mysterious H-alpha recombination emission observed along much of its length that is overly bright (~150-200 milli-Rayleigh) for the known Galactic ultraviolet background (~20-40 mR / [d/55 kpc]^2). In an earlier model, we proposed that a slow shock cascade was operating along the Stream due to its interaction with the extended Galactic hot corona. We find that, for a smooth coronal density profile, this model can explain the bright H-alpha emission if the coronal density satisfies 2 < (n / 10^{-4} cm^{-3}) < 4 at d = 55 kpc. But in view of updated parameters for the Galactic halo and mounting evidence that most of the Stream must lie far beyond the Magellanic Clouds (d>55 kpc), we revisit the shock cascade model in detail. At lower densities, the HI gas is broken down by the shock cascade but mostly mixes with the hot corona without significant recombination. At higher densities, the hot coronal mass (including the other baryonic components) exceeds the baryon budget of the Galaxy. If the H-alpha emission arises from the shock cascade, the upper limit on the smooth coronal density constrains the Stream's mean distance to < 75 kpc. If, as some models indicate, the Stream is even further out, either the shock cascade is operating in a regime where the corona is substantially mass-loaded with recent gas debris, or an entirely different ionization mechanism is responsible.Comment: Significant expansion of the parameter space explored in response to referee's comments. ApJ accepte

Engineering management of large scale systems

The organization of high technology and engineering problem solving, has given rise to an emerging concept. Reasoning principles for integrating traditional engineering problem solving with system theory, management sciences, behavioral decision theory, and planning and design approaches can be incorporated into a methodological approach to solving problems with a long range perspective. Long range planning has a great potential to improve productivity by using a systematic and organized approach. Thus, efficiency and cost effectiveness are the driving forces in promoting the organization of engineering problems. Aspects of systems engineering that provide an understanding of management of large scale systems are broadly covered here. Due to the focus and application of research, other significant factors (e.g., human behavior, decision making, etc.) are not emphasized but are considered

Suggested criteria for evaluating systems engineering methodologies

Systems engineering is the application of mathematical and scientific principles to practical ends in the life-cycle of a system. A methodology for systems engineering is a carefully developed, relatively complex procedure or process for applying these mathematical and scientific principles. There are many systems engineering methodologies (or possibly many versions of a few methodologies) currently in use in government and industry. These methodologies are usually designed to meet the needs of a particular organization. It has been observed, however, that many technical and non-technical problems arise when inadequate systems engineering methodologies are applied by organizations to their systems development projects. Various criteria for evaluating systems engineering methodologies are discussed. Such criteria are developed to assist methodology-users in identifying and selecting methodologies that best fit the needs of the organization

Genetic sensitivity to the bitter taste of 6-n-propylthiouracil (PROP) and its association with Physiological mechanisms controlling Body Mass Index (BMI)

Taste sensitivity to the bitter compound 6-n-propylthiouracil (PROP) is considered a marker for individual differences in taste perception that may influence food preferences and eating behavior, and thereby energy metabolism. This review describes genetic factors that may contribute to PROP sensitivity including: (1) the variants of the TAS2R38 bitter receptor with their different affinities for the stimulus; (2) the gene that controls the gustin protein that acts as a salivary trophic factor for fungiform taste papillae; and (3) other specific salivary proteins that could be involved in facilitating the binding of the PROP molecule with its receptor. In addition, we speculate on the influence of taste sensitivity on energy metabolism, possibly via modulation of the endocannabinoid system, and its possible role in regulating body composition homeostasis

NCC Simulation Model: Simulating the operations of the network control center, phase 2

The simulation of the network control center (NCC) is in the second phase of development. This phase seeks to further develop the work performed in phase one. Phase one concentrated on the computer systems and interconnecting network. The focus of phase two will be the implementation of the network message dialogues and the resources controlled by the NCC. These resources are requested, initiated, monitored and analyzed via network messages. In the NCC network messages are presented in the form of packets that are routed across the network. These packets are generated, encoded, decoded and processed by the network host processors that generate and service the message traffic on the network that connects these hosts. As a result, the message traffic is used to characterize the work done by the NCC and the connected network. Phase one of the model development represented the NCC as a network of bi-directional single server queues and message generating sources. The generators represented the external segment processors. The served based queues represented the host processors. The NCC model consists of the internal and external processors which generate message traffic on the network that links these hosts. To fully realize the objective of phase two it is necessary to identify and model the processes in each internal processor. These processes live in the operating system of the internal host computers and handle tasks such as high speed message exchanging, ISN and NFE interface, event monitoring, network monitoring, and message logging. Inter process communication is achieved through the operating system facilities. The overall performance of the host is determined by its ability to service messages generated by both internal and external processors

A dynamic systems engineering methodology research study. Phase 2: Evaluating methodologies, tools, and techniques for applicability to NASA's systems projects

A study of NASA's Systems Management Policy (SMP) concluded that the primary methodology being used by the Mission Operations and Data Systems Directorate and its subordinate, the Networks Division, is very effective. Still some unmet needs were identified. This study involved evaluating methodologies, tools, and techniques with the potential for resolving the previously identified deficiencies. Six preselected methodologies being used by other organizations with similar development problems were studied. The study revealed a wide range of significant differences in structure. Each system had some strengths but none will satisfy all of the needs of the Networks Division. Areas for improvement of the methodology being used by the Networks Division are listed with recommendations for specific action

Reading First Impact Study: Interim Report

This report, written by Abt Associates and MDRC and published by the U.S. Department of Education's Institute of Education Sciences, finds that Reading First increased the amount of time that teachers spent on the five essential components of reading instruction, as defined by the National Reading Panel. While Reading First did not improve students' reading comprehension on average, there are some indications that some sites had impacts on both instruction and reading comprehension. An overview puts these interim findings in context

Thermal-structural design study of an airframe-integrated Scramjet

Design concepts are developed and evaluated for a cooled structures assembly for the Scramjet engine, for engine subsystems mass, volume, and operating requirements, and for the aircraft/engine interface. A thermal protection system was defined that makes it possible to attain a life of 100 hours and 1000 cycles. The coolant equivalence ratio at the Mach 10 maximum thermal loading condition is 0.6, indicating a capacity for airframe cooling. The mechanical design is feasible for manufacture using conventional materials. For the cooled structures in a six-module engine, the mass per unit capture area is 12.4 KN/sq m. The total weight of a six-module engine assembly including the fuel system is 14.73 KN

Correlation of tellurium inclusions and carrier lifetime in detector grade cadmium zinc telluride

Carrier lifetimes and telluriuminclusion densities in detector grade cadmiumzinc telluride crystals grown by the high pressure Bridgman method were optically measured using pulsed laser microwavecavity perturbation and infrared microscopy. Excess carriers were produced in the material using a pulsed laser with a wavelength of 1064 nm and pulse width of 7 ns, and the electronic decay was measured at room temperature. Spatial mapping of lifetimes and defect densities in cadmiumzinc telluride was performed to determine the relationship between telluriumdefect density and trapping. A strong correlation was found between the volume fraction of telluriuminclusions and the carrier trapping time