Real-Time Frequency Response Estimation from Flight Data

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90729/1/AIAA-2011-6358-848.pd

Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors

Ribosome biogenesis is a key process for maintaining protein synthetic capacity in dividing or growing cells, and requires coordinated production of ribosomal proteins and ribosomal RNA (rRNA), including the processing of the latter. Signalling through mammalian target of rapamycin complex 1 (mTORC1) activates all these processes. Here, we show that, in human cells, impaired rRNA processing, caused by expressing an interfering mutant of BOP1 or by knocking down components of the PeBoW complex elicits activation of mTORC1 signalling. This leads to enhanced phosphorylation of its substrates S6K1 and 4E-BP1, and stimulation of proteins involved in translation initiation and elongation. In particular, we observe both inactivation and downregulation of the eukaryotic elongation factor 2 kinase, which normally inhibits translation elongation. The latter effect involves decreased expression of the eEF2K mRNA. The mRNAs for ribosomal proteins, whose translation is positively regulated by mTORC1 signalling, also remain associated with ribosomes. Therefore, our data demonstrate that disrupting rRNA production activates mTORC1 signalling to enhance the efficiency of the translational machinery, likely to help compensate for impaired ribosome production

The Patriot Journalist: An Examination of the Work of Wisconsin\u27s Dickey Chapelle

Wisconsin journalist Dickey Chapelle is primarily remembered as the first female journalist from the U.S. killed while covering combat. She died while on patrol with the Marines on Nov. 4, 1965 in South Vietnam. Chapelle was repeatedly in Vietnam to cover the war from 1961-1965, but the resulting articles were rarely published. In fact, only three articles from her trips to Laos and Vietnam were published in any major magazine. The evidence demonstrates Chapelle believed her difficulties in finding publishers was the result of gender discrimination. However, Chapelle had no formal education and no training for the work required of a journalist. An examination of her professional correspondence revealed that editors were dissatisfied with her work product due to her unorthodox reporting style, her inability to produce copy related to the assignment she was given, and in some cases her lack of objectivity. Chapelle professed to a sort of \u27see and report\u27 style, but an examination of her private correspondence revealed she had strong anti-communist, pro-interventionist beliefs that led her to tailor articles in order to gain the support of people in the U.S. for the Vietnam War. The evidence demonstrates that Chapelle was ill-prepared for the writing required of a war correspondent during this era. Further, her ideology shaped her reporting, as opposed to her reporting being shaped by events on the ground in a true \u27see and report\u27 style

The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer.

The advent of neuroimaging methodologies, such as functional magnetic resonance imaging (fMRI), has significantly advanced our understanding of the neurophysiological processes supporting a wide spectrum of mind-body approaches to treat pain. A promising self-regulatory practice, mindfulness meditation, reliably alleviates experimentally induced and clinical pain. Yet, the neural mechanisms supporting mindfulness-based pain relief remain poorly characterized. The present review delineates evidence from a spectrum of fMRI studies showing that the neural mechanisms supporting mindfulness-induced pain attenuation differ across varying levels of meditative experience. After brief mindfulness-based mental training (ie, less than 10 hours of practice), mindfulness-based pain relief is associated with higher order (orbitofrontal cortex and rostral anterior cingulate cortex) regulation of low-level nociceptive neural targets (thalamus and primary somatosensory cortex), suggesting an engagement of unique, reappraisal mechanisms. By contrast, mindfulness-based pain relief after extensive training (greater than 1000 hours of practice) is associated with deactivation of prefrontal and greater activation of somatosensory cortical regions, demonstrating an ability to reduce appraisals of arising sensory events. We also describe recent findings showing that higher levels of dispositional mindfulness, in meditation-naïve individuals, are associated with lower pain and greater deactivation of the posterior cingulate cortex, a neural mechanism implicated in self-referential processes. A brief fMRI primer is presented describing appropriate steps and considerations to conduct studies combining mindfulness, pain, and fMRI. We postulate that the identification of the active analgesic neural substrates involved in mindfulness can be used to inform the development and optimization of behavioral therapies to specifically target pain, an important consideration for the ongoing opioid and chronic pain epidemic

Frequent Coamplification of Receptor Tyrosine Kinase and Downstream Signaling Genes in Japanese Primary Gastric Cancer and Conversion in Matched Lymph Node Metastasis

Objective: To establish the gene copy number status of receptor tyrosine kinase (RTK) and downstream signaling (DSS) genes genes in primary gastric cancer (primGC) and matched lymph node metastases (LNmet). Background: Evidence suggests that coamplification between RTKs and DSSs and conversion between primGC and LNmet are associated with resistance to targeted therapy. Methods: DNA from 237 Japanese primGC and 103 matched LNmet was analyzed using a newly developed multiplex ligation-dependent probe amplification (MLPA) probemix to investigate RTK (EGFR, HER2, FGFR2, and MET) and DSS (PIK3CA, KRAS, MYC, and CCNE1) gene copy number status. Results were compared between primGC and LNmet and related to clinicopathological data including survival. Results: A total of 150 (63%) primGC had either RTK or DSS amplification. DSS coamplification was more frequent than RTK coamplification in primGC and LNmets. Moreover, 70 (30%) GC showed a disconcordant RTK and/or DSS gene copy number status between primGC and LNmet, most common was negative conversion for DSS genes (n=40 GC). The presence of RTK amplification in primGC was related to poorer survival in univariate analysis (P=0.04). Conclusions: This is the first and most comprehensive study in gastric cancer investigating the concordance between gene copy number status of targetable RTKs and downstream signaling oncogenes in primGC and LNmets. Future studies need to establish whether the relative high frequency of RTK and DSS coamplification and/or the relative high rate of negative conversion in LNmet can potentially explain recent failures of RTK targeted therapy in gastric cancer patients

Changes in microbiological composition of soils and soil contamination with drug-resistant bacteria caused by the use of sewage sludge in nature

This study evaluated the effect of the use of sewage sludge in nature on biological soil parameters. The study was conducted is field experiment environment (small beds). The sandy soil was fertilized with sewage sludge dried naturally (in heaps) and in solar drying facilities. The fertilization was based on the doses of sewage sludge and manure with the amounts of 10, 20, 30 and 40 Mg/ha. The experiment duration was 3 years. The sanitary status of the soils fertilized with the sludge and manure was evaluated (coliform index, Clostridium perfrinens). Furthermore, the content of pathogenic bacteria was evaluated, with determination of its resistance to first-line antibiotics

Adaptive Flow Control of Low Reynolds Number Aerodynamics Using a Dielectric Barrier Discharge Actuator

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77022/1/AIAA-2009-378-858.pd

Constitutive CD40 signaling in B cells selectively activates the noncanonical NF-κB pathway and promotes lymphomagenesis

CD40, a member of the tumor necrosis factor (TNF) receptor family, plays an essential role in T cell-dependent immune responses. Because CD40 is widely expressed on the surface of tumor cells in various B cell malignancies, deregulated CD40 signaling has been suggested to contribute to lymphomagenesis. In this study, we show that B cell-specific expression of a constitutively active CD40 receptor, in the form of a latent membrane protein 1 (LMP1)/ CD40 chimeric protein, promoted an increase in the number of follicular and marginal zone B cells in secondary lymphoid organs in transgenic mice. The B cells displayed an activated phenotype, prolonged survival and increased proliferation, but were significantly impaired in T cell-dependent immune responses. Constitutive CD40 signaling in B cells induced selective and constitutive activation of the noncanonical NF-κB pathway and the mitogen-activated protein kinases Jnk and extracellular signal-regulated kinase. LMP1/CD40-expressing mice older than 12 mo developed B cell lymphomas of mono- or oligoclonal origin at high incidence, thus showing that the interplay of the signaling pathways induced by constitutive CD40 signaling is sufficient to initiate a tumorigenic process, ultimately leading to the development of B cell lymphomas