Computational Analysis of the Regulation of EGFR by Protein Tyrosine Phosphatases

AbstractThe tyrosine phosphorylated epidermal growth factor receptor (EGFR) initiates numerous cell signaling pathways. Although EGFR phosphorylation levels are ultimately determined by the balance of receptor kinase and protein tyrosine phosphatase (PTP) activities, the kinetics of EGFR dephosphorylation are not well understood. Previous models of EGFR signaling have generally neglected PTP activity or computed PTP activity by considering data that do not fully reveal the kinetics and compartmentalization of EGFR dephosphorylation. We developed a compartmentalized, mechanistic model to elucidate the kinetics of EGFR dephosphorylation and the coupling of this process to phosphorylation-dependent EGFR endocytosis. Model regression against data from HeLa cells for EGFR phosphorylation response to EGFR activation, PTP inhibition, and EGFR kinase inhibition led to the conclusion that EGFR dephosphorylation occurs at the plasma membrane and in the cell interior with a timescale that is smaller than that for ligand-mediated EGFR endocytosis. The model further predicted that sufficiently rapid dephosphorylation of EGFR at the plasma membrane could potentially impede EGFR endocytosis, consistent with recent experimental findings. Overall, our results suggest that PTPs regulate multiple receptor-level phenomena via their action at the plasma membrane and cell interior and point to new possibilities for targeting PTPs for modulation of EGFR dynamics

Generation of optimal trajectories for Earth hybrid pole sitters

A pole-sitter orbit is a closed path that is constantly above one of the Earth's poles, by means of continuous low thrust. This work proposes to hybridize solar sail propulsion and solar electric propulsion (SEP) on the same spacecraft, to enable such a pole-sitter orbit. Locally-optimal control laws are found with a semi-analytical inverse method, starting from a trajectory that satisfies the pole-sitter condition in the Sun-Earth circular restricted three-body problem. These solutions are subsequently used as first guess to find optimal orbits, using a direct method based on pseudospectral transcription. The orbital dynamics of both the pure SEP case and the hybrid case are investigated and compared. It is found that the hybrid spacecraft allows savings on propellant mass fraction. Finally, it is shown that for sufficiently long missions, a hybrid pole-sitter, based on mid-term technology, enables a consistent reduction in the launch mass for a given payload, with respect to a pure SEP spacecraft

Energetics of surface melt in West Antarctica

We use reanalysis data and satellite remote sensing of cloud properties to examine how meteorological conditions alter the surface energy balance to cause surface melt that is detectable in satellite passive microwave imagery over West Antarctica. This analysis can detect each of the three primary mechanisms for inducing surface melt at a specific location: thermal blanketing involving sensible heat flux and/or longwave heating by optically thick cloud cover, all-wave radiative enhancement by optically thin cloud cover, and f&ouml;hn winds. We examine case studies over Pine Island and Thwaites glaciers, which are of interest for ice shelf and ice sheet stability, and over Siple Dome, which is more readily accessible for field work. During January 2015 over Siple Dome we identified a melt event whose origin is an all-wave radiative enhancement by optically thin clouds. During December 2011 over Pine Island and Thwaites glaciers, we identified a melt event caused mainly by thermal blanketing from optically thick clouds. Over Siple Dome, those same 2011 synoptic conditions yielded a thermal-blanketing-driven melt event that was initiated by an impulse of sensible heat flux and then prolonged by cloud longwave heating. The December 2011 synoptic conditions also generated f&ouml;hn winds at a location on the Ross Ice Shelf adjacent to the Transantarctic Mountains, and we analyze this case with additional support from automatic weather station data. In contrast, a late-summer thermal blanketing period over Pine Island and Thwaites glaciers during February 2013 showed surface melt initiated by cloud longwave heating and then prolonged by enhanced sensible heat flux. One limitation thus far with this type of analysis involves uncertainties in the cloud optical properties. Nevertheless, with improvements this type of analysis can enable quantitative prediction of atmospheric stress on the vulnerable Antarctic ice shelves in a steadily warming climate. &nbsp;</p

The lesbian, gay, bisexual and transgender community online: discussions of bullying and self-disclosure in YouTube videos

Computer-mediated communication has become a popular platform for identity construction and experimentation as well as social interaction for those who identify as lesbian, gay, bisexual or transgender (LGBT). The creation of user-generated videos has allowed content creators to share experiences on LGBT topics. With bullying becoming more common amongst LGBT youth, it is important to obtain a greater understanding of this phenomenon. In our study, we report on the analysis of 151 YouTube videos which were identified as having LGBT- and bullying-related content. The analysis reveals how content creators openly disclose personal information about themselves and their experiences in a non-anonymous rhetoric with an unknown public. These disclosures could indicate a desire to seek friendship, support and provide empathy

An overview of ISCAT 2000

The Investigation of Sulfur Chemistry in the Antarctic Troposphere (ISCAT) took place over the timer period of 15 November to 31 December in the year 2000. The study location was the Amundsen Scott Station in Antarctica. ISCAT 2000 defines the second phase of a program designed to explore tropospheric chemistry in Antarctica. As in 1998, the 2000 ISCAT study revealed a strong oxidizing environment at South Pole (SP). During the 2000 investigation, however, the suite of measurements was greatly expanded. These new measurements established the recycling of reactive nitrogen as a critical component of this unique environment. This paper first presents the historical background leading up to the ISCAT 2000 observations; then it focuses on providing a summary of the year 2000 results and contrasts these with those recorded during 1998. Important developments made during the 2000 study included the recording of SP data for several species being emitted from the snowpack. These included NO, H 2O2 and CH2O. In this context, eddy-diffusion flux measurements provided the first quantitative estimates of the SP NO and NOx snow-to-atmosphere fluxes. This study also revealed that HNO 3 and HO2NO2 were major sink species for HOx and NOx radicals. And, it identified the critical factors responsible for SP NO levels exceeding those at other polar sites by nearly an order of magnitude. Finally, it reports on the levels of gas phase sulfur species and provides evidence indicating that the absence of DMS at SP is most likely due to its greatly shorten chemical lifetime in the near vicinity of the plateau. It is proposed that this is due to the influence of NO on the distribution of OH in the lower free troposphere over a region that extends well beyond the plateau itself. Details related to each of the above findings plus others can be found in the 11 accompanying Special Issue papers. © 2004 Elsevier Ltd. All rights reserved

ウィスコンシン ダイガク マディソンコウ ガ ジッシ シテイル ナンキョク ムジン キショウ カンソク (AWS) ケイカク ノ 2011-2012 ネン カキ ノ カツドウ

ウィスコンシン大学マディソン校で推進している南極無人気象観測計画(Antarctic Automatic Weather Station(AWS)program)の32 年目の観測が,2011/2012年の南半球夏期に完了した.無人気象観測網を利用して南極の気象と気候の研究が行われている.今シーズンはロス島周辺域,ロス棚氷,西南極,東南極にわたる領域で活動した.基本的に観測点のデータはアルゴス衛星を中継して配信されるが,今年はロス島周辺域の多くの観測点で,マクマード基地を中継して"Freewave modem"を通して配信された.各無人気象観測点報告には,現在設置されている測器と動作状況が含まれる.また,無人気象観測計画の全体像を,野外活動の実施状況に沿って示す.During the 2011-2012 austral summer, the Antarctic Automatic Weather Station (AWS) program at the University of Wisconsin?Madison completed its 32nd year of observations. Ongoing studies utilizing the network include topics in Antarctic meteorology and climate studies. This field season consisted of work throughout the Ross Island area, the Ross Ice Shelf, West Antarctica, and East Antarctica. Argos satellite transmissions are the primary method for relaying station data, but throughout this year, a number of stations in the Ross Island area have been converted to Freewave modems, with their data being relayed through McMurdo station. Each AWS station report contains information regarding the instrumentation currently installed and the work performed at each site. An overview of the AWS applications is included along with field work accomplished

Automatic Weather Station (AWS) Program operated by the University of Wisconsin-Madison during the 2012-2013 field season: Challenges and Successes

ウィスコンシン大学マディソン校で推進している南極無人気象観測計画（Antarctic Automatic Weather Station（AWS）program）の，2012-2013年のフィールド調査および結果の概要を報告する．今期はAWS 観測網の歴史上，特異なシーズンであった．ロス島地域が温暖であったことは氷上滑走路の利用に影響を及ぼし，いくつかの設営面での制約に直面した． 柔軟な計画により，限られた条件下でAWS サービルを最大化し，自動観測ネットワークへの要求に対応する最善の手段をとることができた．This report reviews 2012-2013 field season activities of the University of Wisconsin-Madison＇s Antarctic Automatic Weather Station (AWS) program, summarizes the science that these sites are supporting, and outlines the factors that impact the number of AWS sites serviced in any given field season. The 2012-2013 austral summer season was unusual in the AWS network history. Challenges encountered include, but are not limited to, warmer than normal conditions in the Ross Island area impacting airfield operations, changes to logistical procedures, and competition for shared resources. A flexible work plan provides the best means for taking on these challenges while maximizing AWS servicing efforts under restricted conditions and meeting the need for routine servicing that maintaining an autonomous observing network demands

Telerounding: A Scoping Review and Implications for Future Healthcare Practice

Telerounding is slated to become an important avenue for future healthcare practice. As utilization of telerounding is increasing, a review of the literature is necessary to distill themes and identify critical considerations for the implementation of telerounding. We provide evidence of the utility of telerounding and considerations to support its implementation in future healthcare practice based on a scoping review. Method: We collected articles from nine scientific databases from the earliest dated available articles to August 2020. We identified whether each article centered on telerounding policies, regulations, or practice. We also organized information from each article and sorted themes into four categories: sample characteristics, technology utilized, study constructs, and research outcomes. Results: We identified 21 articles related to telerounding that fit our criteria. All articles emphasized telerounding practice. Most articles reported data collected from surgical wards, had adult samples, and utilized robotic telerounding systems. Most articles reported null effects or positive effects on their measured variables. Discussion: Providers and patients can benefit from the effective implementation of telerounding. Telerounding can support patient care by reducing travel expenses and opportunities for infection. Evidence suggests that telerounding can reduce patient length of stay. Patients and providers are willing to utilize telerounding, but patient willingness is influenced by age and education. Telerounding does not appear to negatively impact satisfaction or patient care. Organizations seeking to implement telerounding systems must consider education for their providers, logistics associated with hardware and software, scheduling, and characteristics of the organizational context that can support telerounding. Considerations provided in this article can mitigate difficulties associated with the implementation of telerounding

p53Psi is a transcriptionally inactive p53 isoform able to reprogram cells toward a metastatic-like state

Although much is known about the underlying mechanisms of p53 activity and regulation, the factors that influence the diversity and duration of p53 responses are not well understood. Here we describe a unique mode of p53 regulation involving alternative splicing of the TP53 gene. We found that the use of an alternative 3' splice site in intron 6 generates a unique p53 isoform, dubbed p53Psi. At the molecular level, p53Psi is unable to bind to DNA and does not transactivate canonical p53 target genes. However, like certain p53 gain-of-function mutants, p53Psi attenuates the expression of E-cadherin, induces expression of markers of the epithelial-mesenchymal transition, and enhances the motility and invasive capacity of cells through a unique mechanism involving the regulation of cyclophilin D activity, a component of the mitochondrial inner pore permeability. Hence, we propose that p53Psi encodes a separation-of-function isoform that, although lacking canonical p53 tumor suppressor/transcriptional activities, is able to induce a prometastatic program in a transcriptionally independent manner