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Kurokawa, Manabu,Kim, Jiyeon,Geradts, Joseph,Matsuura, Kenkyo,Liu, Liu,Ran, Xu,Xia, Wenle,Ribar, Thomas J.,Henao, Ricardo,Dewhirst, Mark W.,Kim, Wun-Jae,Lucas, Joseph E.,Wang, Shaomeng,Spector, Neil L AAAS 2013 Science signaling Vol.6 No.274
<P><B>Breaking Down to Build Resistance</B></P><P>Chemotherapeutic resistance often arises because of the rewiring of signaling pathways in cancer cells. Kurokawa <I>et al.</I> found that the ubiquitin E3 ligase MDM2 triggered the breakdown of another ubiquitin E3 ligase, HUWE1. In breast cancer cells that died when exposed to the HER2 (human epidermal growth factor receptor 2) EGFR (epidermal growth factor receptor) tyrosine kinase inhibitor lapatinib, MDM2 was degraded, which enabled HUWE1 to trigger the degradation of a prosurvival protein and promote assembly and activation of a protein complex required for the execution of cell death. However, MDM2 degradation did not occur in lapatinib-resistant breast cancer cells, and thus, the abundance of HUWE1 was decreased, promoting cell survival. In a mouse xenograft model, an inhibitor of MDM2 reduced the growth of tumors generated from lapatinib-resistant breast cancer cells. Thus, MDM2 could be targeted to circumvent resistance to lapatinib in breast cancers.</P>
Performance of reduced bit-depth acquisition for optical frequency domain imaging
Goldberg, Brian D.,Vakoc, Benjamin J.,Oh, Wang-Yuhl,Suter, Melissa J.,Waxman, Sergio,Freilich, Mark I.,Bouma, Brett E.,Tearney, Guillermo J. The Optical Society 2009 Optics express Vol.17 No.19
<P>High-speed optical frequency domain imaging (OFDI) has enabled practical wide-field microscopic imaging in the biological laboratory and clinical medicine. The imaging speed of OFDI, and therefore the field of view, of current systems is limited by the rate at which data can be digitized and archived rather than the system sensitivity or laser performance. One solution to this bottleneck is to natively digitize OFDI signals at reduced bit depths, e.g., at 8-bit depth rather than the conventional 12-14 bit depth, thereby reducing overall bandwidth. However, the implications of reduced bit-depth acquisition on image quality have not been studied. In this paper, we use simulations and empirical studies to evaluate the effects of reduced depth acquisition on OFDI image quality. We show that image acquisition at 8-bit depth allows high system sensitivity with only a minimal drop in the signal-to-noise ratio compared to higher bit-depth systems. Images of a human coronary artery acquired in vivo at 8-bit depth are presented and compared with images at higher bit-depth acquisition.</P>
Saslow, Sarah A.,Um, Wooyong,Pearce, Carolyn I.,Engelhard, Mark H.,Bowden, Mark E.,Lukens, Wayne,Leavy, Ian I.,Riley, Brian J.,Kim, Dong-Sang,Schweiger, Michael J.,Kruger, Albert A. American Chemical Society 2017 Environmental science & technology Vol.51 No.15
<P>Technetium (Tc) remains a priority remediation concern due to persistent challenges, including mobilization due to rapid reoxidation of immobilized Tc, and competing comingled contaminants, e.g., Cr(VI), that inhibit Tc(VII) reduction and incorporation into stable mineral phases. Here Fe(OH)(2)(s) is investigated as a comprehensive solution for overcoming these challenges, by serving as both the reductant, (Fe(II)), and the immobilization agent to form Tc-incorporated magnetite (Fe3O4). Trace metal analysis suggests removal of Tc(VII) and Cr(VI) from solution occurs simultaneously; however, complete removal and reduction of Cr(VI) is achieved earlier than the removal/reduction of comingled Tc(VII). Bulk oxidation state analysis of the final magnetite solid phase by XANES shows that the majority of Tc is Tc(IV), which is corroborated by XPS measurements. Furthermore, EXAFS results show successful, albeit partial, Tc(IV) incorporation into magnetite octahedral sites. Cr XPS analysis indicates reduction to Cr(III) and the formation of a Cr-incorporated spinel, Cr2O3, and Cr(OH)(3) phases. Spinel (modeled as Fe3O4), goethite (alpha-FeOOH), and feroxyhyte (delta-FeOOH) are detected in all reacted final solid phase samples analyzed by XRD. Incorporation of Tc(IV) has little effect on the spinel lattice structure. Reaction of Fe(OH)(2)(s) in the presence of Cr(III) results in the formation of a spinel phase that is a solid solution between magnetite (Fe3O4) and chromite (FeCr2O4).</P>
Evolution of Process and Outcome Measures during an Enhanced Recovery after Thoracic Surgery Program
Alex Lee,Nazgol Seyednejad,Yaseen Al Lawati,Amanda Mattice,Caitlin Anstee,Mark Legacy,Sebastien Gilbert,Donna E. Maziak,Ramanadhan S. Sundaresan,Patrick J. Villeneuve,Calvin Thompson,Andrew J. E. Seel 대한심장혈관흉부외과학회 2022 Journal of Chest Surgery (J Chest Surg) Vol.55 No.2
Background: A time course analysis was undertaken to evaluate how perioperative process- of-care and outcome measures evolved after implementation of an enhanced recovery after thoracic surgery (ERATS) program. Methods: Outcome and process-of-care measures were compared between patients undergoing major elective thoracic surgery during a 9-month pre-ERATS implementation period to those at 1–3, 4–6, and 7–9 months post-ERATS implementation. Outcome measures included length of stay, the 30-day readmission rate, 30-day emergency department visits, and minor and major adverse events. Process measures included first time to activity, out-of-bed, ambulation, fluid diet, diet as tolerated, as well as removal of the first and last chest tube, epidural, patient-controlled analgesia, and Foley and intravenous catheters. Results: In total, 704 patients (352 pre-ERATS, 352 post-ERATS) were included. Mobilization- related process measures, including time to first activity (16.5 vs. 6.8 hours, p<0.001), out-of-bed (17.6 vs. 8.9 hours, p<0.001), and ambulation (32.4 vs. 25.4 hours, p=0.04) saw statistically significant improvements by 1–3 months post-ERATS implementation compared to pre-ERATS. Time to Foley removal improved by 4–6 months post-ERATS (19.5 vs. 18.2 hours, p=0.003). Outcome measures, including the 30-day readmission rate and emergency department visits, steadily decreased post-ERATS. By 7–9 months post-ERATS, both minor (18.2% vs. 7.9%, p=0.009) and major (13.6% vs. 4.4%, p=0.007) adverse events demonstrated statistically significant improvements. Length of stay trended towards improvement from 6.2 days pre-ERATS to 4.8 days by 7–9 months post-ERATS (p=0.06). Conclusion: The adoption of ERATS led to improvements in multiple process-of-care measures, which may collectively and gradually achieve optimization of clinical outcomes.
Type VI secretion is a major virulence determinant in <i>Burkholderia mallei</i>
Schell, Mark A.,Ulrich, Ricky L.,Ribot, Wilson J.,Brueggemann, Ernst E.,Hines, Harry B.,Chen, Dan,Lipscomb, Lyla,Kim, H. Stanley,Mrá,zek, Jan,Nierman, William C.,DeShazer, David Blackwell Publishing Ltd 2007 Molecular microbiology Vol.64 No.6
<P><B>Summary</B></P><P> <I>Burkholderia mallei</I> is a host‐adapted pathogen and a category B biothreat agent. Although the <I>B. mallei</I> VirAG two‐component regulatory system is required for virulence in hamsters, the virulence genes it regulates are unknown. Here we show with expression profiling that overexpression of <I>virAG</I> resulted in transcriptional activation of ∼60 genes, including some involved in capsule production, actin‐based intracellular motility, and type VI secretion (T6S). The 15 genes encoding the major sugar component of the homopolymeric capsule were up‐expressed > 2.5‐fold, but capsule was still produced in the absence of <I>virAG</I>. Actin tail formation required <I>virAG</I> as well as <I>bimB</I>, <I>bimC</I> and <I>bimE</I>, three previously uncharacterized genes that were activated four‐ to 15‐fold when VirAG was overproduced. Surprisingly, actin polymerization was found to be dispensable for virulence in hamsters. In contrast, genes encoding a T6S system were up‐expressed as much as 30‐fold and mutations in this T6S gene cluster resulted in strains that were avirulent in hamsters. SDS‐PAGE and mass spectrometry demonstrated that BMAA0742 was secreted by the T6S system when <I>virAG</I> was overexpressed. Purified His‐tagged BMAA0742 was recognized by glanders antiserum from a horse, a human and mice, indicating that this Hcp‐family protein is produced <I>in vivo</I> during infection.</P>
Joby J. Thoppil,Lauren K. Stewart,Leland Pung,Kristen E. Nordenholz,Carlos A. Camargo Jr.,D. Mark Courtney,Jeffrey A. Kline,on behalf of the RECOVER Network 대한비만학회 2022 Journal of obesity & metabolic syndrome Vol.31 No.3
Background: Increased body mass index (BMI) and metabolic syndrome (MetS) have been associated with adverse outcomes in viral syndromes. We sought to examine associations of increased BMI and MetS on several clinical outcomes in patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: The registry of suspected COVID-19 in emergency care (RECOVER) is an observational study of SARS-CoV-2-tested patients (n=27,051) across 155 United States emergency departments (EDs). We used multivariable logistic regression to test for associations of several predictor variables with various clinical outcomes. Results: We found that a BMI ≥30 kg/m2 increased odds of SARS-CoV-2 test positivity (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.23–1.38), while MetS reduced odds of testing positive for SARS-CoV-2 (OR, 0.76; 95% CI, 0.71–0.82). Adjusted multivariable analysis found that MetS was significantly associated with the need for admission (OR, 2.11; 95% CI, 1.89–2.37), intensive care unit (ICU) care (OR, 1.58; 95% CI, 1.40–1.78), intubation (OR, 1.46; 95% CI, 1.28–1.66), mortality (OR, 1.29; 95% CI, 1.13–1.48), and venous thromboembolism (OR, 1.51; 95% CI, 1.07–2.13) in SARS-CoV-2-positive patients. Similarly, BMI ≥40 kg/m2 was significantly associated with ICU care (OR, 1.97; 95% CI, 1.65–2.35), intubation (OR, 2.69; 95% CI, 2.22–3.26), and mortality (OR, 1.50; 95% CI, 1.22–1.84). Conclusion: In this large nationwide sample of ED patients, we report a significant association of both high BMI and composite MetS with poor outcomes in SARS-CoV-2-positive patients. Findings suggest that composite MetS profile may be a more universal predictor of adverse disease outcomes, while the impact of BMI is more heavily modulated by SARS-CoV-2 status.
우주비행 직후 인체 심혈관계의 혈류역학적 변화에 대한 수치적 연구
심은보(E. B. Shim),고형종(H. J. Ko),T. Heldt,R. D. Kamm,R. G. Mark 한국전산유체공학회 2000 한국전산유체공학회 학술대회논문집 Vol.2000 No.10
Orthostatic stress in human cardiovascular system following spaceflight remains a critical problem in the current lifescience space program. The study presented in this paper is part of an<br/> ongoing effort to use mathematical models to investigate the effects of gravitational stresses on the cardiovascular system of normals and microgravity adapted individuals. We employ a twelve compartment lumped parameter representation of the hemodynamic system coupled to setpoint models of the arterial baroreflex and the cardiopulmonary reflex to investigate the transient response of heart rate to orthostatic stress. We simulate current hypotheses concerning the mechanisms underlying postspaceflight orthostatic intolerance over a range of physiologically reasonable values and compare the simulations to astronaut stand test data pre-and postflight.