Methodology for the Integration of Economic, Environmental and Functional Issues in Complex Product Design

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Identification of poly(ADP-ribose)polymerase-1 and Ku70/Ku80 as transcriptional regulators of S100A9 gene expression

BACKGROUND: S100 proteins, a multigenic family of non-ubiquitous cytoplasmic Ca(2+)-binding proteins, have been linked to human pathologies in recent years. Dysregulated expression of S100 proteins, including S100A9, has been reported in the epidermis as a response to stress and in association with neoplastic disorders. Recently, we characterized a regulatory element within the S100A9 promotor, referred to as MRE that drives the S100A9 gene expression in a cell type-specific, activation- and differentiation-dependent manner (Kerkhoff et al. (2002) J. Biol. Chem. 277, 41879–41887). RESULTS: In the present study, we investigated transcription factors that bind to MRE. Using the MRE motif for a pull-down assay, poly(ADP-ribose)polymerase-1 (PARP-1) and the heterodimeric complex Ku70/Ku80 were identified by mass spectrometry and confirmed by chromatin immunoprecipitation. Furthermore, TPA-induced S100A9 gene expression in HaCaT keratinocytes was blocked after the pharmacologic inhibition of PARP-1 with 1,5-isoquinolinediol (DiQ). CONCLUSION: The candidates, poly(ADP-ribose)polymerase-1 (PARP-1) and the heterodimeric complex Ku70/Ku80, are known to participate in inflammatory disorders as well as tumorgenesis. The latter may indicate a possible link between S100 and inflammation-associated cancer

A high-flux BEC source for mobile atom interferometers

Quantum sensors based on coherent matter-waves are precise measurement devices whose ultimate accuracy is achieved with Bose-Einstein condensates (BEC) in extended free fall. This is ideally realized in microgravity environments such as drop towers, ballistic rockets and space platforms. However, the transition from lab-based BEC machines to robust and mobile sources with comparable performance is a challenging endeavor. Here we report on the realization of a miniaturized setup, generating a flux of $4 \times 10^5$ quantum degenerate $^{87}$Rb atoms every 1.6$\,$s. Ensembles of $1 \times 10^5$ atoms can be produced at a 1$\,$Hz rate. This is achieved by loading a cold atomic beam directly into a multi-layer atom chip that is designed for efficient transfer from laser-cooled to magnetically trapped clouds. The attained flux of degenerate atoms is on par with current lab-based BEC experiments while offering significantly higher repetition rates. Additionally, the flux is approaching those of current interferometers employing Raman-type velocity selection of laser-cooled atoms. The compact and robust design allows for mobile operation in a variety of demanding environments and paves the way for transportable high-precision quantum sensors.Comment: 22 pages, 6 figure

Effectiveness of performance appraisal:an integrated framework

Based on a robust analysis of the existing literature on performance appraisal (PA), this paper makes a case for an integrated framework of effectiveness of performance appraisal (EPA). To achieve this, it draws on the expanded view of measurement criteria of EPA, i.e. purposefulness, fairness and accuracy, and identifies their relationships with ratee reactions. The analysis reveals that the expanded view of purposefulness includes more theoretical anchors for the purposes of PA and relates to various aspects of human resource functions, e.g. feedback and goal orientation. The expansion in the PA fairness criterion suggests certain newly established nomological networks, which were ignored in the past, e.g. the relationship between distributive fairness and organization-referenced outcomes. Further, refinements in PA accuracy reveal a more comprehensive categorization of rating biases. Coherence among measurement criteria has resulted in a ratee reactions-based integrated framework, which should be useful for both researchers and practitioners

Progressive resistance training in cachectic head and neck cancer patients undergoing radiotherapy: a randomized controlled pilot feasibility trial

Abstract Background Cancer cachexia is a prevalent symptom of head and neck neoplasms. The reduction in skeletal muscle mass is one of the main characteristics which can lead to poor physical functioning. The purposes of this pilot randomized controlled trial were to determine the feasibility of progressive resistance training in cachectic head and neck cancer patients during radiotherapy and to explore possible risks and benefits. Methods Twenty cachectic participants with head and neck cancer receiving radiation were randomized to obtain either a machine supported progressive resistance training (n = 10) or usual care (n = 10). The training took place 3 times weekly for 30 min. Intervention included 3 exercises for major muscle groups with 8–12 repetition maximum for 3 sets each. Bioelectrical impedance analysis, hand-held dynamometry, Six-Minute Walk Test and standardized questionnaires for fatigue and quality of life were used for evaluating outcomes at baseline before radiotherapy (t1), after 7 weeks of radiotherapy (t2) and 8 weeks after the end of radiotherapy (t3). Results All participants (n = 20) completed the trial. No serious adverse events occurred. At the initial assessment the cachectic patients had already lost 7.1 ± 5.2% of their body weight. General fatigue (score 10.7 ± 3.3) and reduced quality of life (score 71.3 ± 20.6) were prevalent in cachectic head and neck cancer patients even before radiotherapy. An average improvement of weight loading for leg press (+ 19.0%), chest press (+ 29.8%) and latissimus pull-down (+ 22.8%) was possible in the intervention group. Participants had at least 13 training sessions. The outcome measures showed nonsignificant changes at t2 and t3, but a trend for a better course of general fatigue and quality of life at t2 in the intervention group. Conclusions Despite advanced tumor stage and burdensome treatment the intervention adherence is excellent. Progressive resistance training in cachectic head and neck cancer patients during radiotherapy seems to be safe and feasible and may have beneficial effects of general fatigue and quality of life. Trial registration ClinicalTrials.gov, NCT03524755. Registered 15 May 2018 - Retrospectively registered