Colorectal Cancer Stem Cells Are Enriched in Xenogeneic Tumors Following Chemotherapy

Patients generally die of cancer after the failure of current therapies to eliminate residual disease. A subpopulation of tumor cells, termed cancer stem cells (CSC), appears uniquely able to fuel the growth of phenotypically and histologically diverse tumors. It has been proposed, therefore, that failure to effectively treat cancer may in part be due to preferential resistance of these CSC to chemotherapeutic agents. The subpopulation of human colorectal tumor cells with an ESA(+)CD44(+) phenotype are uniquely responsible for tumorigenesis and have the capacity to generate heterogeneous tumors in a xenograft setting (i.e. CoCSC). We hypothesized that if non-tumorigenic cells are more susceptible to chemotherapeutic agents, then residual tumors might be expected to contain a higher frequency of CoCSC.Xenogeneic tumors initiated with CoCSC were allowed to reach approximately 400 mm(3), at which point mice were randomized and chemotherapeutic regimens involving cyclophosphamide or Irinotecan were initiated. Data from individual tumor phenotypic analysis and serial transplants performed in limiting dilution show that residual tumors are enriched for cells with the CoCSC phenotype and have increased tumorigenic cell frequency. Moreover, the inherent ability of residual CoCSC to generate tumors appears preserved. Aldehyde dehydrogenase 1 gene expression and enzymatic activity are elevated in CoCSC and using an in vitro culture system that maintains CoCSC as demonstrated by serial transplants and lentiviral marking of single cell-derived clones, we further show that ALDH1 enzymatic activity is a major mediator of resistance to cyclophosphamide: a classical chemotherapeutic agent.CoCSC are enriched in colon tumors following chemotherapy and remain capable of rapidly regenerating tumors from which they originated. By focusing on the biology of CoCSC, major resistance mechanisms to specific chemotherapeutic agents can be attributed to specific genes, thereby suggesting avenues for improving cancer therapy

Applicant perspectives during selection

We provide a comprehensive but critical review of research on applicant reactions to selection procedures published since 2000 (n = 145), when the last major review article on applicant reactions appeared in the Journal of Management. We start by addressing the main criticisms levied against the field to determine whether applicant reactions matter to individuals and employers (“So what?”). This is followed by a consideration of “What’s new?” by conducting a comprehensive and detailed review of applicant reaction research centered upon four areas of growth: expansion of the theoretical lens, incorporation of new technology in the selection arena, internationalization of applicant reactions research, and emerging boundary conditions. Our final section focuses on “Where to next?” and offers an updated and integrated conceptual model of applicant reactions, four key challenges, and eight specific future research questions. Our conclusion is that the field demonstrates stronger research designs, with studies incorporating greater control, broader constructs, and multiple time points. There is also solid evidence that applicant reactions have significant and meaningful effects on attitudes, intentions, and behaviors. At the same time, we identify some remaining gaps in the literature and a number of critical questions that remain to be explored, particularly in light of technological and societal changes

The Design and Fabrication of a Load-Attenuating Launcher for Multiple Air-Launched UAS

Current air-launched unmanned aerial systems (UAS) are often limited by the quantity that can be carried and their interactions with the host aircraft. This study proposes a device which increases the number of UAS carried on an aircraft while reducing the loads imparted on the airframe and improving other launch characteristics. After defining the customer requirements and constraints of the problem, an iterative design process was used to reach a final prototype. The design incorporates elastomeric springs to reduce the impulsive loads on the host aircraft. Further analysis led to the selection of 6061-T6 aluminum as the primary material in the device. We developed an instrumentation package consisting of strain gauges and inertial measurement units and a testing apparatus was designed. After testing, the team found that the mount reduced the force on the airframe by 34.3%, which was below the initial goal. Furthermore, as input force increased, the force reduction increased. Therefore, the design will meet the force reduction requirement at the expected launch loads. The processes and selected design used here will lead into follow-on testing with the goal of producing an airworthy design that satisfies the demands of the problem

Small Adaptive Flight Control Systems for UAVs Using FPGA/DSP Technology

Presented at the AIAA 3rd "Unmanned Unlimited" Technical Conference, Workshop and Exhibit 20 - 23 September 2004, Chicago, Illinois.Copyright © 2004 by The Authors. Published by the American Institute of Aeronautics and Astronautics, Inc., with permission.Future small UAVs will require enhanced capabilities like seeing and avoiding obstacles, tolerating unpredicted flight conditions, interfacing with payload sensors, tracking moving targets, and cooperating with other manned and unmanned systems. Cross-platform commonality to simplify system integration and training of personnel is also desired. A small guidance, navigation, and control system has been developed and tested. It employs Field Programmable Gate Array (FPGA) and Digital Signal Processor (DSP) technology to satisfy the requirements for more advanced vehicle behavior in a small package. Having these two processors in the system enables custom vehicle interfacing and fast sequential processing of high-level control algorithms. This paper focuses first on the design aspects of the hardware and the low-level software. Discussion of flight test experience with the system controlling both an unmanned helicopter and an 11-inch ducted fan follow

REM Sleep Behavior Disorder in Parkinson’s Disease: Change in Cognitive, Psychiatric, and Functional Outcomes from Baseline to 16–47-Month Follow-Up

ObjectiveRapid Eye Movement Sleep Behavior Disorder (RBD) is common in Parkinson's Disease (PD) and is associated with cognitive impairment; however, the majority of the evidence on the impact of RBD on multidomain cognitive batteries in PD is cross-sectional. This study evaluated the longitudinal impact of probable RBD (pRBD) on cognitive, psychiatric, and functional outcomes in people with PD.MethodCase-control study. A total of 65 people with PD completed the study protocol at baseline and 16-to-47-month follow-up. Participants were classified as pRBD+ (n = 25) or pRBD- (n = 40) based on an established cutoff of 6 on the RBD Sleep Questionnaire (RBDSQ). Participants also completed a) comprehensive cognitive testing, b) self-report measures of depression, anxiety, and apathy, and c) performance-based and other-report forms of instrumental activities of daily living.ResultsBaseline mean age was 67.8 (SD = 8.1; range = 45-86) and baseline mean years of education was 16.4 (SD = 2.1; range = 12-20). The two groups did not differ on measured demographic characteristics. Baseline mean T-scores for cognitive tests were in the average range (46-55). Hierarchical linear models tested group differences in cognitive and functional decline from baseline to follow-up, controlling for appropriate demographic and psychiatric variables. Compared to the pRBD- group, pRBD+ participants showed greater decline in attention/working memory (r = -0.31; p = 0.01) and UPSA financial skills (r = -0.31; p = 0.01). No other group differences approached significance.ConclusionsRBD may differentially affect attention/working memory and financial abilities in PD. Results underscore the importance of regular RBD screening in older adults with PD in order to triage symptomatic patients to appropriate cognitive and medical interventions