Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration.

Nematode EAK-7 (enhancer-of-akt-1-7) regulates dauer formation and controls life span; however, the function of the human ortholog mammalian EAK-7 (mEAK-7) is unknown. We report that mEAK-7 activates an alternative mechanistic/mammalian target of rapamycin (mTOR) signaling pathway in human cells, in which mEAK-7 interacts with mTOR at the lysosome to facilitate S6K2 activation and 4E-BP1 repression. Despite interacting with mTOR and mammalian lethal with SEC13 protein 8 (mLST8), mEAK-7 does not interact with other mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2) components; however, it is essential for mTOR signaling at the lysosome. This phenomenon is distinguished by S6 and 4E-BP1 activity in response to nutrient stimulation. Conventional S6K1 phosphorylation is uncoupled from S6 phosphorylation in response to mEAK-7 knockdown. mEAK-7 recruits mTOR to the lysosome, a crucial compartment for mTOR activation. Loss of mEAK-7 results in a marked decrease in lysosomal localization of mTOR, whereas overexpression of mEAK-7 results in enhanced lysosomal localization of mTOR. Deletion of the carboxyl terminus of mEAK-7 significantly decreases mTOR interaction. mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration

The Role of Interpretive Evaluation in Engineering Information Systems Requirements

The requirements for complex systems inevitably change continuously. Any successful software or information systems engineering approach needs to observe this simple fact. This paper argues for the critical importance of formative evaluation activities in any non-sequential, or learning-based RE process. We argue that evaluation with its focus on understanding and interpreting the evaluation results, is distinct from measurement. We also outline how evaluation activities can be performed from an interpretivist perspective, in a way that systematically informs formative evaluation activities during gradual, experimental requirements engineering activities

mEAK-7 Forms an Alternative mTOR Complex with DNA-PKcs in Human Cancer.

MTOR associated protein, eak-7 homolog (mEAK-7), activates mechanistic target of rapamycin (mTOR) signaling in human cells through an alternative mTOR complex to regulate S6K2 and 4E-BP1. However, the role of mEAK-7 in human cancer has not yet been identified. We demonstrate that mEAK-7 and mTOR signaling are strongly elevated in tumor and metastatic lymph nodes of patients with non-small-cell lung carcinoma compared with those of patients with normal lung or lymph tissue. Cancer stem cells, CD44+/CD90+ cells, yield elevated mEAK-7 and activated mTOR signaling. mEAK-7 is required for clonogenic potential and spheroid formation. mEAK-7 associates with DNA-dependent protein kinase catalytic subunit isoform 1 (DNA-PKcs), and this interaction is increased in response to X-ray irradiation to regulate S6K2 signaling. DNA-PKcs pharmacologic inhibition or genetic knockout reduced S6K2, mEAK-7, and mTOR binding with DNA-PKcs, resulting in loss of S6K2 activity and mTOR signaling. Therefore, mEAK-7 forms an alternative mTOR complex with DNA-PKcs to regulate S6K2 in human cancer cells

Classification and Management of Upland, Riparian, and Wetland Sites of USDI Bureau of Land Management’s Miles City Field Office, Eastern Montana USA

A system is presented for the classification and management of uplands, riparian, and wetland sites within the USDI Bureau of Land Management’s Miles City Field Office in eastern Montana. The Miles City Field of the USDI Bureau of Land Management lies within the northern Great Plains and occupies approximately the eastern 1/3 of Montana. The concepts and terminology used in this document are consistent with usage proposed by Daubenmire (1952, 1968, 1978), and are used in numerous other vegetation-based ecological site classifications for North America. A dichotomous key utilizing indicator plant species is provided for field identification of the habitat types and major seral plant communities (for example community types) that are stable for time frames relevant to land management decisions. The habitat types (for example ecological site types) are identified first in the key. If this is not possible, the key then identifies the major seral community types. Within the description of each community type is a discussion of possible habitat types for the site. Each “type” includes detailed information for managing a particular site. The work utilized 1,126 sample plots resulting in a total of 96 different plant communities identified to either the habitat type (and phase) or community type level. There were 62 identified riparian/wetland types and 28 upland types. In addition, six types are types that can occur in both riparian/wetland and upland situations. There were a total of 663 unique species recorded for the 1,126 sampled stands. Of the 663 species, 551 (83 percent) were native, and 112 (17 percent) were introduced or contain an introduced element. The document can be downloaded from www.ecologicalsolutionsgroup.com

Web-Based Simulation: Evolution or Revolution?

ACM Transactions on Modeling and Computer Simulation, Vol. 10, No. 1, January 2000, Pages 3–17

Is Extension Relevant for the 21st Century?

As a 90-year-old artifact of the days when an agrarian economy dominated society, is it possible for Extension to still be relevant? As the primary outreach and public service function of land-grant universities, the relevance of Extension is tied to the perception and reality of the relevance of these host institutions. Did the recent ECOP report A Vision for the 21st Century and other ECOP statements address whether Extension remains relevant to the 21st century context? Extension educators are assisting communities of place and of interest and involving more university and agency colleagues in responding to changing citizen education needs

Analytical Treatment of the Oscillating Yukawa Potential

Using a suitable Laguerre basis set that ensures a tridiagonal matrix representation of the reference Hamiltonian, we were able to evaluate in closed form the matrix elements of the generalized Yukawa potential with complex screening parameter. This enabled us to treat analytically both the cosine and sine-like Yukawa potentials on equal footing and compute their bound states spectrum as the eigenvalues of the associated analytical matrix representing their Hamiltonians. Finally we used a carefully designed complex scaling method to evaluate the resonance energies and compared our results satisfactorily with those obtained in the literature.Comment: 8 pages 2 table

Small-Angle Excess Scattering: Glassy Freezing or Local Orientational Ordering?

We present Monte Carlo simulations of a dense polymer melt which shows glass-transition-like slowing-down upon cooling, as well as a build up of nematic order. At small wave vectors q this model system shows excess scattering similar to that recently reported for light-scattering experiments on some polymeric and molecular glass-forming liquids. For our model system we can provide clear evidence that this excess scattering is due to the onset of short-range nematic order and not directly related to the glass transition.Comment: 3 Pages of Latex + 4 Figure

National Seismic System Science Plan

Recent developments in digital communication and seismometry are allowing seismologists to propose revolutionary new ways to reduce vulnerability from earthquakes, volcanoes, and tsunamis, and to better understand these phenomena as well as the basic structure and dynamics of the Earth. This document provides a brief description of some of the critical new problems that can be addressed using modem digital seismic networks. It also provides an overview of existing seismic networks and suggests ways to integrate these together into a National Seismic System. A National Seismic System will consist of a number of interconnected regional networks (such as southern California, central and northern California, northeastern United States, northwestern United States, and so on) that are jointly operated by Federal, State, and private seismological research institutions. Regional networks will provide vital information concerning the hazards of specific regions. Parts of these networks will be linked to provide uniform rapid response on a national level (the National Seismic Network). A National Seismic System promises to significantly reduce societal risk to earthquake losses and to open new areas of fundamental basic research. The following is a list of some of the uses of a National Seismic System