Controls Considerations for Turbine Active Clearance Control

NASA Technical Reports Server (NTRS)

Melcher, Kevin J.

2004-01-01

This presentation discusses active control of turbine tip clearance from a control systems perspective. It is a subset of charts that were presented at the 2003 meeting of the International Society of Air Breathing Engines which was held August 31 through September 5 in Cleveland, Ohio. The associated reference paper is cited at the end of the presentation. The presentation describes active tip clearance control research being conducted by NASA to improve turbine engine systems. The target application for this effort is commercial aircraft engines. However, it is believed that the technologies developed as part of this research will benefit a broad spectrum of current and future turbomachinery. The first part of the presentation discusses the concept of tip clearance, problems associated with it, and the benefits of controlling it. It lays out a framework for implementing tip clearance controls that enables the implementation to progress from purely analytical to hardware-in-the-loop to fully experimental. And it briefly discusses how the technologies developed will be married to the previously described ACC Test Rig for hardware-in-the-loop demonstrations. The final portion of the presentation, describes one of the key technologies in some detail by presenting equations and results for a functional dynamic model of the tip clearance phenomena. As shown, the model exhibits many of the clearance dynamics found in commercial gas turbine engines. However, initial attempts to validate the model identified limitations that are being addressed to make the model more realistic.

Baptist Hospital East conducts successful target marketing.

PubMed

Rees, Tom

2003-01-01

A targeted marketing program at Baptist Hospital East, Louisville, Ky., has worked successfully to strengthen the hospital's relationships with the employers and employees in the hospital's marketing area. Also, the program strengthens Baptist East's BaptistWorx occupational medicine program and complements the hospital's traditional advertising.

Lactate clearance cut off for early mortality prediction in adult sepsis and septic shock patients

NASA Astrophysics Data System (ADS)

Sinto, R.; Widodo, D.; Pohan, H. T.

2018-03-01

Previous lactate clearance cut off for early mortality prediction in sepsis and septic shock patient was determined by consensus from small sample size-study. We investigated the best lactate clearance cut off and its ability to predict early mortality in sepsis and septic shock patients. This cohort study was conducted in Intensive Care Unit of CiptoMangunkusumo Hospital in 2013. Patients’ lactate clearance and eight other resuscitationendpoints were recorded, and theoutcome was observed during the first 120 hours. The clearance cut off was determined using receiver operating characteristic (ROC) analysis, and its ability was investigated with Cox’s proportional hazard regression analysis using other resuscitation endpoints as confounders. Total of 268 subjects was included, of whom 70 (26.11%) subjects died within the first 120 hours. The area under ROC of lactate clearance to predict early mortality was 0.78 (95% % confidence interval [CI] 0.71-0.84) with best cut off was <7.5% (sensitivity and specificity 88.99% and 81.4% respectively). Compared with group achieving lactate clearance target, group not achieving lactate clearance target had to increase early mortality risk (adjusted hazard ratio 13.42; 95%CI 7.19-25.07). In conclusion, the best lactate clearance cut off as anearly mortality predictor in sepsis and septic shock patients is 7.5%.

Creatinine clearance test

MedlinePlus

Serum creatinine clearance; Kidney function - creatinine clearance; Renal function - creatinine clearance ... the body entirely by the kidneys. If kidney function is abnormal, creatinine level increases in the blood ...

Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

PubMed

Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

2016-02-01

ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International

Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia

PubMed Central

Li, June; van der Wal, Dianne E.; Zhu, Guangheng; Xu, Miao; Yougbare, Issaka; Ma, Li; Vadasz, Brian; Carrim, Naadiya; Grozovsky, Renata; Ruan, Min; Zhu, Lingyan; Zeng, Qingshu; Tao, Lili; Zhai, Zhi-min; Peng, Jun; Hou, Ming; Leytin, Valery; Freedman, John; Hoffmeister, Karin M.; Ni, Heyu

2015-01-01

Immune thrombocytopenia (ITP) is a common bleeding disorder caused primarily by autoantibodies against platelet GPIIbIIIa and/or the GPIb complex. Current theory suggests that antibody-mediated platelet destruction occurs in the spleen, via macrophages through Fc–FcγR interactions. However, we and others have demonstrated that anti-GPIbα (but not GPIIbIIIa)-mediated ITP is often refractory to therapies targeting FcγR pathways. Here, we generate mouse anti-mouse monoclonal antibodies (mAbs) that recognize GPIbα and GPIIbIIIa of different species. Utilizing these unique mAbs and human ITP plasma, we find that anti-GPIbα, but not anti-GPIIbIIIa antibodies, induces Fc-independent platelet activation, sialidase neuraminidase-1 translocation and desialylation. This leads to platelet clearance in the liver via hepatocyte Ashwell–Morell receptors, which is fundamentally different from the classical Fc–FcγR-dependent macrophage phagocytosis. Importantly, sialidase inhibitors ameliorate anti-GPIbα-mediated thrombocytopenia in mice. These findings shed light on Fc-independent cytopenias, designating desialylation as a potential diagnostic biomarker and therapeutic target in the treatment of refractory ITP. PMID:26185093

Selectively increasing the clearance of protein-bound uremic solutes

PubMed Central

Luo, Frank J.-G.; Plummer, Natalie S.; Hostetter, Thomas H.; Meyer, Timothy W.

2012-01-01

Background. The toxicity of bound solutes could be better evaluated if we could adjust the clearance of such solutes independent of unbound solutes. This study assessed whether bound solute clearances can be increased while maintaining urea clearance constant during the extended hours of nocturnal dialysis. Methods. Nine patients on thrice-weekly nocturnal dialysis underwent two experimental dialysis treatments 1 week apart. The experimental treatments were designed to provide the same urea clearance while providing widely different bound solute clearance. One treatment employed a large dialyzer and high dialyzate flow rate (Qd) of 800 mL/min while blood flow (Qb) was 270 mL/min. The other treatment employed a smaller dialyzer and Qd of 300 mL/min while Qb was 350 mL/min. Results. Treatment with the large dialyzer and higher Qd greatly increased the clearances of the bound solutes p-cresol sulfate (PCS: 27 ± 9 versus 14 ± 6 mL/min) and indoxyl sulfate (IS: 26 ± 8 versus 14 ± 5 mL/min) without altering the clearance of urea (204 ± 20 versus 193 ± 16 mL/min). Increasing PCS and IS clearances increased the removal of these solutes (PCS: 375 ± 200 versus 207 ± 86 mg/session; IS: 201 ± 137 versus 153 ± 74 mg/session), while urea removal was not different. Conclusions. The removal of bound solutes can thus be increased by raising the dialyzate flow and dialyzer size above the low levels sufficient to achieve target Kt/Vurea during extended treatment. Selectively increasing the clearance of bound solutes provides a potential means to test their toxicity. PMID:22231033

Mechanisms of failed apoptotic cell clearance by phagocyte subsets in cardiovascular disease

PubMed Central

2013-01-01

Recent evidence in humans indicate that defective phagocytic clearance of dying cells is linked to progression of advanced atherosclerotic lesions, the precursor to atherothrombosis, ischemic heart disease, and leading cause of death in the industrialized world. During atherogenesis, apoptotic cell turnover in the vascular wall is counterbalanced by neighboring phagocytes with high clearance efficiency, thereby limiting cellularity and maintaining lesion integrity. However, as lesions mature, phagocytic removal of apoptotic cells (efferocytosis) becomes defective, leading to secondary necrosis, expansion of plaque necrotic cores, and susceptibility to rupture. Recent genetic causation studies in experimental rodents have implicated key molecular regulators of efferocytosis in atherosclerotic progression. These include MER tyrosine kinase (MERTK), milk fat globule-EGF factor 8 (MFGE8), and complement C1q. At the cellular level, atheromata are infiltrated by a heterogenous population of professional phagocytes, comprised of monocytes, differentiated macrophages, and CD11c+ dendritic-like cells. Each cell type is characterized by disparate clearance efficiencies and varying activities of key phagocytic signaling molecules. It is in this context that we outline a working model whereby plaque necrosis and destabilization is jointly promoted by (1) direct inhibition of core phagocytic signaling pathways and (2) expansion of phagocyte subsets with poor clearance capacity. Towards identifying targets for promoting efficient apoptotic cell clearance and resolving inflammation in atherosclerosis and during ischemic heart disease and post myocardial infarction, this review will discuss potential in vivo suppressors of efferocytosis at each stage of clearance and how these putative interventional targets may differentially affect uptake at the level of vascular phagocyte subsets. PMID:20552278

Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging.

PubMed

Zhang, Liang; Thurber, Greg M

2016-02-01

Quantitative molecular imaging of beta cell mass (BCM) would enable early detection and treatment monitoring of type 1 diabetes. The glucagon-like peptide-1 (GLP-1) receptor is an attractive target due to its beta cell specificity and cell surface location. We quantitatively investigated the impact of plasma clearance and receptor internalization on targeting efficiency in healthy B6 mice. Four exenatide-based probes were synthesized that varied in molecular weight, binding affinity, and plasma clearance. The GLP-1 receptor internalization rate and in vivo receptor expression were quantified. Receptor internalization (54,000 receptors/cell in vivo) decreased significantly within minutes, reducing the benefit of a slower-clearing agent. The multimers and albumin binding probes had higher kidney and liver uptake, respectively. Slow plasma clearance is beneficial for GLP-1 receptor peptide therapeutics. However, for exendin-based imaging of islets, down-regulation of the GLP-1 receptor and non-specific background uptake result in a higher target-to-background ratio for fast-clearing agents.

TAM receptors in apoptotic cell clearance, autoimmunity, and cancer.

PubMed

Nguyen, Khanh-Quynh; Tsou, Wen-I; Kotenko, Sergei; Birge, Raymond B

2013-08-01

Receptor tyrosine kinases, Tyro-3, Axl and Mer, collectively designated as TAM, are involved in the clearance of apoptotic cells. TAM ligands, Gas6 and Protein S, bind to the surfaces of apoptotic cells, and at the same time, interact directly with TAM expressed on phagocytes, impacting the engulfment and clearance of apoptotic cells and debris. The well-tuned and balanced actions of TAM may affect a variety of human pathologies including autoimmunity, retinal degeneration, and cancer. This article emphasizes some of the emerging findings and mechanistic insights into TAM functions that are clinically relevant and possibly therapeutically targeted.

Importance of target-mediated drug disposition for small molecules.

PubMed

Smith, Dennis A; van Waterschoot, Robert A B; Parrott, Neil J; Olivares-Morales, Andrés; Lavé, Thierry; Rowland, Malcolm

2018-06-18

Target concentration is typically not considered in drug discovery. However, if targets are expressed at relatively high concentrations and compounds have high affinity, such that most of the drug is bound to its target, in vitro screens can give unreliable information on compound affinity. In vivo, a similar situation will generate pharmacokinetic (PK) profiles that deviate greatly from those normally expected, owing to target binding affecting drug distribution and clearance. Such target-mediated drug disposition (TMDD) effects on small molecules have received little attention and might only become apparent during clinical trials, with the potential for data misinterpretation. TMDD also confounds human microdosing approaches by providing therapeutically unrepresentative PK profiles. Being aware of these phenomena will improve the likelihood of successful drug discovery and development. Copyright © 2018. Published by Elsevier Ltd.

Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging

PubMed Central

Zhang, Liang; Thurber, Greg M.

2016-01-01

Purpose Quantitative molecular imaging of beta cell mass (BCM) would enable early detection and treatment monitoring of type-1 diabetes. The glucagon like peptide-1 (GLP-1) receptor is an attractive target due to its beta cell specificity and cell surface location. We quantitatively investigated the impact of plasma clearance and receptor internalization on targeting efficiency in healthy B6 mice. Procedures Four exenatide-based probes were synthesized that varied in molecular weight, binding affinity, and plasma clearance. The GLP-1 receptor internalization rate and in vivo receptor expression were quantified. Results Receptor internalization (54,000 receptors/cell in vivo) decreased significantly within minutes, reducing the benefit of a slower clearing agent. The multimers and albumin binding probes had higher kidney and liver uptake, respectively. Conclusions Slow plasma clearance is beneficial for GLP-1 receptor peptide therapeutics. However, for exendin-based imaging of islets, downregulation of the GLP-1 receptor and non-specific background uptake result in a higher TBR for fast-clearing agents. PMID:26194012

ICP-MS analysis of lanthanide-doped nanoparticles: A quantitative and multiplexing approach to investigate biodistribution, blood clearance, and targeting

NASA Astrophysics Data System (ADS)

Crayton, Samuel

The rapidly progressing field of nanotechnology promises to revolutionize healthcare in the 21st century, with applications in the prevention, diagnosis, and treatment of a wide range of diseases. However, before nanoparticulate agents can be brought into clinical use, they must first be developed, optimized, and evaluated in animal models. In the typical pre-clinical paradigm, almost all of the optimization is done at the in vitro level, with only a few select agents reaching the level of animal studies. Since only one experimental nanoparticle formulation can be investigated in a single animal, and in vivo experiments have relatively higher complexity, cost, and time requirements, it is not feasible to evaluate a very large number of agents at the in vivo stage. A major drawback of this approach, however, is that in vitro assays do not always accurately predict how a nanoparticle will perform in animal studies. Therefore, a method that allows many agents to be evaluated in a single animal subject would allow for much more efficient and predictive optimization of nanoparticles. We have found that by incorporating lanthanide tracer metals into nanoparticle formulations, we are successfully able to use inductively coupled plasma mass spectrometry (ICP-MS) to quantitatively determine a nanoparticle's blood clearance kinetics, biodistribution, and tumor delivery. This approach was applied to evaluate both passive and active tumor targeting, as well as metabolically directed targeting of nanoparticles to low pH tumor microenvironments. Importantly, we found that these in vivo measurements could be made for many nanoparticle formulations simultaneously, in single animals, due to the high-order multiplexing capability of mass spectrometry. This approach allowed for efficient and reproducible comparison of performance between different nanoparticle formulations, by eliminating the effects of subject-to-subject variability. In the future, we envision that this "higher

An integrated approach to identify normal tissue expression of targets for antibody-drug conjugates: case study of TENB2

PubMed Central

Boswell, C Andrew; Mundo, Eduardo E; Firestein, Ron; Zhang, Crystal; Mao, Weiguang; Gill, Herman; Young, Cynthia; Ljumanovic, Nina; Stainton, Shannon; Ulufatu, Sheila; Fourie, Aimee; Kozak, Katherine R; Fuji, Reina; Polakis, Paul; Khawli, Leslie A; Lin, Kedan

2013-01-01

Background and Purpose The success of antibody-drug conjugates (ADCs) depends on the therapeutic window rendered by the differential expression between normal and pathological tissues. The ability to identify and visualize target expression in normal tissues could reveal causes for target-mediated clearance observed in pharmacokinetic characterization. TENB2 is a prostate cancer target associated with the progression of poorly differentiated and androgen-independent tumour types, and ADCs specific for TENB2 are candidate therapeutics. The objective of this study was to locate antigen expression of TENB2 in normal tissues, thereby elucidating the underlying causes of target-mediated clearance. Experimental Approach A series of pharmacokinetics, tissue distribution and mass balance studies were conducted in mice using a radiolabelled anti-TENB2 ADC. These data were complemented by non-invasive single photon emission computed tomography – X-ray computed tomography imaging and immunohistochemistry. Key Results The intestines were identified as a saturable and specific antigen sink that contributes, at least in part, to the rapid target-mediated clearance of the anti-TENB2 antibody and its drug conjugate in rodents. As a proof of concept, we also demonstrated the selective disposition of the ADC in a tumoural environment in vivo using the LuCaP 77 transplant mouse model. High tumour uptake was observed despite the presence of the antigen sink, and antigen specificity was confirmed by antigen blockade. Conclusions and Implications Our findings provide the anatomical location and biological interpretation of target-mediated clearance of anti-TENB2 antibodies and corresponding drug conjugates. Further investigations may be beneficial in addressing the relative contributions to ADC disposition from antigen expression in both normal and pathological tissues. PMID:22889168

An integrated approach to identify normal tissue expression of targets for antibody-drug conjugates: case study of TENB2.

PubMed

Boswell, C Andrew; Mundo, Eduardo E; Firestein, Ron; Zhang, Crystal; Mao, Weiguang; Gill, Herman; Young, Cynthia; Ljumanovic, Nina; Stainton, Shannon; Ulufatu, Sheila; Fourie, Aimee; Kozak, Katherine R; Fuji, Reina; Polakis, Paul; Khawli, Leslie A; Lin, Kedan

2013-01-01

The success of antibody-drug conjugates (ADCs) depends on the therapeutic window rendered by the differential expression between normal and pathological tissues. The ability to identify and visualize target expression in normal tissues could reveal causes for target-mediated clearance observed in pharmacokinetic characterization. TENB2 is a prostate cancer target associated with the progression of poorly differentiated and androgen-independent tumour types, and ADCs specific for TENB2 are candidate therapeutics. The objective of this study was to locate antigen expression of TENB2 in normal tissues, thereby elucidating the underlying causes of target-mediated clearance. A series of pharmacokinetics, tissue distribution and mass balance studies were conducted in mice using a radiolabelled anti-TENB2 ADC. These data were complemented by non-invasive single photon emission computed tomography - X-ray computed tomography imaging and immunohistochemistry. The intestines were identified as a saturable and specific antigen sink that contributes, at least in part, to the rapid target-mediated clearance of the anti-TENB2 antibody and its drug conjugate in rodents. As a proof of concept, we also demonstrated the selective disposition of the ADC in a tumoural environment in vivo using the LuCaP 77 transplant mouse model. High tumour uptake was observed despite the presence of the antigen sink, and antigen specificity was confirmed by antigen blockade. Our findings provide the anatomical location and biological interpretation of target-mediated clearance of anti-TENB2 antibodies and corresponding drug conjugates. Further investigations may be beneficial in addressing the relative contributions to ADC disposition from antigen expression in both normal and pathological tissues. © 2012 Genentech, Inc.. British Journal of Pharmacology © 2012 The British Pharmacological Society.

[Correlation index amylase-creatinine clearance to endogenous creatinine clearance in severe preeclampsia].

PubMed

Vázquez Rodríguez, Juan Gustavo; Cruz Cruz, Polita del Rocío; Márquez Hubert, Elizabeth

2009-07-01

Tubular lesion may cause acute renal insufficiency in pregnant patients with severe preeclampsia. To describe the correlation between the amylase/creatinine clearance ratio and endogenous creatinine depuration in pregnant patients with severe preeclampsia. Transversal study (pilot study) twenty eight women with pregnancies of 20 to 40 weeks complicated by severe preeclampsia were studied. Subjects had serum and urine creatinine and amylase determinations to calculate the amylase/creatinine clearance ratio (%). According to the results, two groups were formed: group A (> 3%) and group B (< or = 3%). The correlation between amylase/creatinine clearance ratio and endogenous creatinine depuration was evaluated. measures of central tendency and dispersion, Student's t-test, Pearson correlation coefficient (r) and linear regression were used. Group A included 23 cases (82%) and group B included 5 cases (18%). Amylase/creatinine clearance ratio (%) for group A was 5.22 +/- 1.6 and for group B was 2.41 +/- 0.41 (p = 0.001). The endogenous creatinine depuration (mL /min. /1.73 m2 SC) for group A was 105.6 +/- 9.71 and for group B was 132.10 +/- 7.95 (p = 0.54). The r between amylase/creatinine clearance ratio and endogenous creatinine depuration for group A was -0.43 and for group B was -0.25. A moderately significant negative correlation exists between amylase/creatinine clearance ratio and endogenous creatinine depuration.

Guide star targeting success for the HEAO-B observatory

NASA Technical Reports Server (NTRS)

Farrenkopf, R. L.; Hoffman, D. P.

1977-01-01

The statistics associated with the successful selection and acquisition of guide stars as attitude benchmarks for use in reorientation maneuvers of the HEAO-B observatory are considered as a function of the maneuver angle, initial attitude uncertainties, and the pertinent celestial region. Success likelihoods in excess of 0.99 are predicted assuming anticipated gyro and star tracker error sources. The maneuver technique and guide star selection constraints are described in detail. The results presented are specialized numerically to the HEAO-B observatory. However, the analytical techniques developed are considered applicable to broader classes of spacecraft requiring celestial targeting.

Impairment of paravascular clearance pathways in the aging brain.

PubMed

Kress, Benjamin T; Iliff, Jeffrey J; Xia, Maosheng; Wang, Minghuan; Wei, Helen S; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason A; Plog, Benjamin A; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

2014-12-01

In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2-3 months), middle-aged (10-12 months), and old (18-20 months) wild-type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence. Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid-β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates. © 2014 American Neurological Association.

Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance?

PubMed

Udy, Andrew A; Lipman, Jeffrey; Jarrett, Paul; Klein, Kerenaftali; Wallis, Steven C; Patel, Kashyap; Kirkpatrick, Carl M J; Kruger, Peter S; Paterson, David L; Roberts, Michael S; Roberts, Jason A

2015-01-30

The aim of this study was to explore the impact of augmented creatinine clearance and differing minimum inhibitory concentrations (MIC) on piperacillin pharmacokinetic/pharmacodynamic (PK/PD) target attainment (time above MIC (fT>MIC)) in critically ill patients with sepsis receiving intermittent dosing. To be eligible for enrolment, critically ill patients with sepsis had to be receiving piperacillin-tazobactam 4.5 g intravenously (IV) by intermittent infusion every 6 hours for presumed or confirmed nosocomial infection without significant renal impairment (defined by a plasma creatinine concentration greater than 171 μmol/L or the need for renal replacement therapy). Over a single dosing interval, blood samples were drawn to determine unbound plasma piperacillin concentrations. Renal function was assessed by measuring creatinine clearance (CLCR). A population PK model was constructed, and the probability of target attainment (PTA) for 50% and 100% fT>MIC was calculated for varying MIC and CLCR values. In total, 48 patients provided data. Increasing CLCR values were associated with lower trough plasma piperacillin concentrations (P < 0.01), such that with an MIC of 16 mg/L, 100% fT>MIC would be achieved in only one-third (n = 16) of patients. Mean piperacillin clearance was approximately 1.5-fold higher than in healthy volunteers and correlated with CLCR (r = 0.58, P < 0.01). A reduced PTA for all MIC values, when targeting either 50% or 100% fT>MIC, was noted with increasing CLCR measures. Standard intermittent piperacillin-tazobactam dosing is unlikely to achieve optimal piperacillin exposures in a significant proportion of critically ill patients with sepsis, owing to elevated drug clearance. These data suggest that CLCR can be employed as a useful tool to determine whether piperacillin PK/PD target attainment is likely with a range of MIC values.

14 CFR 25.925 - Propeller clearance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Propeller clearance. 25.925 Section 25.925... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances with the airplane at maximum weight, with the most adverse...

14 CFR 23.925 - Propeller clearance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Propeller clearance. 23.925 Section 23.925... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances, with the airplane at the most...

14 CFR 23.925 - Propeller clearance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Propeller clearance. 23.925 Section 23.925... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances, with the airplane at the most...

14 CFR 23.925 - Propeller clearance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Propeller clearance. 23.925 Section 23.925... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances, with the airplane at the most...

14 CFR 25.925 - Propeller clearance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Propeller clearance. 25.925 Section 25.925... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances with the airplane at maximum weight, with the most adverse...

14 CFR 25.925 - Propeller clearance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Propeller clearance. 25.925 Section 25.925... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances with the airplane at maximum weight, with the most adverse...

14 CFR 25.925 - Propeller clearance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Propeller clearance. 25.925 Section 25.925... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances with the airplane at maximum weight, with the most adverse...

14 CFR 23.925 - Propeller clearance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Propeller clearance. 23.925 Section 23.925... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances, with the airplane at the most...

Testing of a Microwave Blade Tip Clearance Sensor at the NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Woike, Mark R.; Roeder, James W.; Hughes, Christopher E.; Bencic, Timothy J.

2009-01-01

The development of new active tip clearance control and structural health monitoring schemes in turbine engines and other types of rotating machinery requires sensors that are highly accurate and can operate in a high-temperature environment. The use of a microwave sensor to acquire blade tip clearance and tip timing measurements is being explored at the NASA Glenn Research Center. The microwave blade tip clearance sensor works on principles that are very similar to a short-range radar system. The sensor sends a continuous microwave signal towards a target and measures the reflected signal. The phase difference of the reflected signal is directly proportional to the distance between the sensor and the target being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in turbine engines. The use of microwave sensors for this application is a new concept. Techniques on calibrating the sensors along with installation effects are not well quantified as they are for other sensor technologies. Developing calibration techniques and evaluating installation effects are essential in using these sensors to make tip clearance and tip timing measurements. As a means of better understanding these issues, the microwave sensors were used on a benchtop calibration rig, a large axial vane fan, and a turbofan. Background on the microwave tip clearance sensor, an overview of their calibration, and the results from their use on the axial vane fan and the turbofan will be presented in this paper.

Testing of a Microwave Blade Tip Clearance Sensor at the NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Woike, Mark R.; Roeder, James W.; Hughes, Christopher E.; Bencic, Timothy J.

2009-01-01

The development of new active tip clearance control and structural health monitoring schemes in turbine engines and other types of rotating machinery requires sensors that are highly accurate and can operate in a high temperature environment. The use of a microwave sensor to acquire blade tip clearance and tip timing measurements is being explored at the NASA Glenn Research Center. The microwave blade tip clearance sensor works on principles that are very similar to a short range radar system. The sensor sends a continuous microwave signal towards a target and measures the reflected signal. The phase difference of the reflected signal is directly proportional to the distance between the sensor and the target being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in turbine engines. The use of microwave sensors for this application is a new concept. Techniques on calibrating the sensors along with installation effects are not well quantified as they are for other sensor technologies. Developing calibration techniques and evaluating installation effects are essential in using these sensors to make tip clearance and tip timing measurements. As a means of better understanding these issues, the microwave sensors were used on a bench top calibration rig, a large axial vane fan, and a turbofan. Background on the microwave tip clearance sensor, an overview of their calibration, and the results from their use on the axial vane fan and the turbofan will be presented in this paper.

Impairment of paravascular clearance pathways in the aging brain

PubMed Central

Kress, Benjamin T.; Iliff, Jeffrey J.; Xia, Maosheng; Wang, Minghuan; Wei, Helen; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason; Plog, Benjamin A.; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

2014-01-01

Objective In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal and interstitial fluids. Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular cerebrospinal fluid (CSF) pathways. The Objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. Methods CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy while interstitial solute clearance was evaluated by radio-tracer clearance assays in young (2–3 month), middle age (10–12 month) and old (18–20 month) wild type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function were evaluated by immunofluorescence. Results Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparechamally injected amyloid β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. Interpretation We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of mis-folded protein aggregates. PMID:25204284

Ginsenoside compound K promotes β-amyloid peptide clearance in primary astrocytes via autophagy enhancement.

PubMed

Guo, Jinhui; Chang, Li; Zhang, Xin; Pei, Sujuan; Yu, Meishuang; Gao, Jianlian

2014-10-01

The aim of the present study was to investigate the effect of ginsenoside compound K on β-amyloid (Aβ) peptide clearance in primary astrocytes. Aβ degradation in primary astrocytes was determined using an intracellular Aβ clearance assay. Aggregated LC3 in astrocyte cells, which is a marker for the level of autophagy, was detected using laser scanning confocal microscope. The effect of compound K on the mammalian target of rapamycin (mTOR)/autophagy pathway was determined using western blot analysis, and an enzyme-linked immunosorbent assay was used for Aβ detection. The results demonstrated that compound K promoted the clearance of Aβ and enhanced autophagy in primary astrocytes. In addition, it was found that phosphorylation of mTOR was inhibited by compound K, which may have contributed to the enhanced autophagy. In conclusion, compound K promotes Aβ clearance by enhancing autophagy via the mTOR signaling pathway in primary astrocytes.

Freeform lens generation for quasi-far-field successive illumination targets

NASA Astrophysics Data System (ADS)

Zhuang, Zhenfeng; Thibault, Simon

2018-07-01

A predefined mapping to tailor one or more freeform surfaces is employed to build a freeform illumination system. The emergent rays from the light source corresponding to the prescribed target mesh for a pre-determined lighting distance are mapped by a point-to-point algorithm with respect to the freeform optics, which involves limiting design flexibility. To tackle the problem of design limitation and find the optimum design results, a freeform lens is exploited to produce the desired rectangular illumination distribution at successive target planes at quasi-far-field lighting distances. It is generated using numerical solutions to find out an initial starting point, and an appropriate approach to obtain variables for parameterization of the freeform surface is introduced. The relative standard deviation, which is a useful figure of merit for the analysis, is set up as merit function with respect to illumination non-uniformity at the successive sampled target planes. Therefore, the irradiance distribution in terms of the specific lighting distance range can be ensured by the proposed scheme. A design example of a freeform illumination system, composed of a spherical surface and a freeform surface, is given to produce desired irradiance distribution within the lighting distance range. An optical performance with low non-uniformity and high efficiency is achieved. Compared with the conventional approach, the uniformity of the sampled targets is dramatically enhanced; meanwhile, a design result with a large tolerance of LED size is offered.

Optimization of protein and peptide drugs based on the mechanisms of kidney clearance.

PubMed

Huang, Jiaguo; Wu, Huizi

2018-05-30

Development of proteins and peptides into drugs has been considered as a promising strategy to target certain diseases. However, only few proteins and peptides has been approved as new drugs into the market each year. One major problem is that proteins and peptides often exhibit short plasma half-life times, which limits the application for their clinical use. In most cases a short half-life time is not effective to deliver sufficient amount of drugs to the target organs and tissues, which is generally caused by fast renal clearance and low plasma stability due to proteolytic degradation during systemic circulation, because the most common clearance pathway of small proteins and peptides is through glomerular filtration by the kidneys. In this review, enzymatic degradation of proteins and peptides were discussed. Furthermore, several approaches to lengthen the half-life of peptides and proteins drugs based on the unique structures of glomerular capillary wall and the mechanisms of glomerular filtration were summarized, such as increasing the size and hydrodynamic diameter; increasing the negative charge to delay the filtration; increasing plasma protein binding to decrease plasma clearance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dual Target Search is Neither Purely Simultaneous nor Purely Successive.

PubMed

Cave, Kyle R; Menneer, Tamaryn; Nomani, Mohammad S; Stroud, Michael J; Donnelly, Nick

2017-08-31

Previous research shows that visual search for two different targets is less efficient than search for a single target. Stroud, Menneer, Cave and Donnelly (2012) concluded that two target colours are represented separately based on modeling the fixation patterns. Although those analyses provide evidence for two separate target representations, they do not show whether participants search simultaneously for both targets, or first search for one target and then the other. Some studies suggest that multiple target representations are simultaneously active, while others indicate that search can be voluntarily simultaneous, or switching, or a mixture of both. Stroud et al.'s participants were not explicitly instructed to use any particular strategy. These data were revisited to determine which strategy was employed. Each fixated item was categorised according to whether its colour was more similar to one target or the other. Once an item similar to one target is fixated, the next fixated item is more likely to be similar to that target than the other, showing that at a given moment during search, one target is generally favoured. However, the search for one target is not completed before search for the other begins. Instead, there are often short runs of one or two fixations to distractors similar to one target, with each run followed by a switch to the other target. Thus, the results suggest that one target is more highly weighted than the other at any given time, but not to the extent that search is purely successive.

Transient FTY720 treatment promotes immune-mediated clearance of a chronic viral infection.

PubMed

Premenko-Lanier, Mary; Moseley, Nelson B; Pruett, Sarah T; Romagnoli, Pablo A; Altman, John D

2008-08-14

For a wide variety of microbial pathogens, the outcome of the infection is indeterminate. In some individuals the microbe is cleared, but in others it establishes a chronic infection, and the factors that tip this balance are often unknown. In a widely used model of chronic viral infection, C57BL/6 mice clear the Armstrong strain of lymphocytic choriomeningitis virus (LCMV), but the clone 13 strain persists. Here we show that the Armstrong strain induces a profound lymphopenia at days 1-3 after infection, but the clone 13 strain does not. If we transiently augment lymphopenia by treating the clone-13-infected mice with the drug FTY720 at days 0-2 after infection, the mice successfully clear the infection by day 30. Clearance does not occur when CD4 T cells are absent at the time of treatment, indicating that the drug is not exerting direct antiviral effects. Notably, FTY720 treatment of an already established persistent infection also leads to viral clearance. In both models, FTY720 treatment preserves or augments LCMV-specific CD4 and CD8 T-cell responses, a result that is counter-intuitive because FTY720 is generally regarded as a new immunosuppressive agent. Because FTY720 targets host pathways that are completely evolutionarily conserved, our results may be translatable into new immunotherapies for the treatment of chronic microbial infections in humans.

Semen amyloids participate in spermatozoa selection and clearance.

PubMed

Roan, Nadia R; Sandi-Monroy, Nathallie; Kohgadai, Nargis; Usmani, Shariq M; Hamil, Katherine G; Neidleman, Jason; Montano, Mauricio; Ständker, Ludger; Röcker, Annika; Cavrois, Marielle; Rosen, Jared; Marson, Kara; Smith, James F; Pilcher, Christopher D; Gagsteiger, Friedrich; Sakk, Olena; O'Rand, Michael; Lishko, Polina V; Kirchhoff, Frank; Münch, Jan; Greene, Warner C

2017-06-27

Unlike other human biological fluids, semen contains multiple types of amyloid fibrils in the absence of disease. These fibrils enhance HIV infection by promoting viral fusion to cellular targets, but their natural function remained unknown. The similarities shared between HIV fusion to host cell and sperm fusion to oocyte led us to examine whether these fibrils promote fertilization. Surprisingly, the fibrils inhibited fertilization by immobilizing sperm. Interestingly, however, this immobilization facilitated uptake and clearance of sperm by macrophages, which are known to infiltrate the female reproductive tract (FRT) following semen exposure. In the presence of semen fibrils, damaged and apoptotic sperm were more rapidly phagocytosed than healthy ones, suggesting that deposition of semen fibrils in the lower FRT facilitates clearance of poor-quality sperm. Our findings suggest that amyloid fibrils in semen may play a role in reproduction by participating in sperm selection and facilitating the rapid removal of sperm antigens.

Dual Targeting of Amyloid-beta Clearance and Neuroinflammation as a Novel Therapeutic Approach against Alzheimer's Disease

NASA Astrophysics Data System (ADS)

Batarseh, Yazan S.

Amyloid-beta (Abeta) cascade hypothesis suggests that Alzheimer's disease (AD) is related to an imbalance between the production and clearance of Abeta peptide. Sporadic AD has been related to faulty clearance of Abeta. Accumulation of Abeta oligomers (Abetao) has been linked to several downstream toxic effects including neuroinflammation, synaptic loss, and cellular death. Abeta transport across the blood-brain barrier (BBB) is one of the primary pathways for reducing Abeta load in the brain, which work hand in hand with other parenchymal mechanisms to reduce Abeta levels including intra and extracellular degradation by a family of Abeta degrading enzymes. Established AD drugs, such as the cholinesterase inhibitor donepezil, have been reported to have several additional non-cholinergic effects that alter Abeta pathology; reduce Abeta load, anti-inflammatory response, and attenuate synaptic loss. However, their limited effect only lead to minor improvements in AD symptoms without improving the prognosis of the disease. The lack of effective medical treatment for AD led to several studies focusing on establishing new therapeutic approaches to reduce Abeta pathology. We aimed to identify and characterize natural products that are capable of enhancing the BBB clearance of Abeta in addition to reducing neuroinflammation. Our first project was to investigate the role of oleocanthal (one of the active ingredients in extra-virgin olive oil; EVOO) on attenuating Abeta toxic effects on neurons and astrocytes. We developed Abeta oligomers (Abetao) induced inflammatory environment by exposing neurons and astrocytes to accumulative doses of Abetao to investigate oleocanthal effect on modulating Abetao pathological changes in neurons and astrocytes. Our findings demonstrated oleocanthal prevented Abetao-induced synaptic proteins, SNAP-25 and PSD-95, down-regulation in neurons, attenuated Abetao-induced inflammation, and restored glutamine transporter (GLT1) and glucose

UXO clearance operation in Laos

NASA Astrophysics Data System (ADS)

Sato, Motoyuki; Kadoya, Yoshihiko

2018-04-01

Laos is one of the most seriously contaminated countries by UXO. Most of the UXO are cluster bombs, used in 1960- 70's. There is historical political background about the UXO problems in Laos. Currently, The clearance of UXO is significantly important for future economic development for Laos. It affects not only local inhabitants, but it will affects national economy. For example, UXO clearance in mountainous area can promote construction of roads, and Laos has a good possibility to be the center of transportation in Indo-Chia region. We have started a research project for evaluation of impact of UXO clearance in Laos, "The economic impact and the technological development for the elimination of unexploded ordnance (UXO) elimination in Laos". Lao National Unexploded Ordnance Programme (UXO Lao) is working in the nine most impacted provinces nationwide and it clears land for agriculture and community purposes. We recently visited Laos and observed the UXO clearance procedure conducted by UXOLAO. The technical survey for UXO clearance site to determine for operation, UXO detection by using metal detectors are organized by UXO Lao. In this paper, we will report the technical aspects of the UXO clearance in Laos.

Human-in-the-Loop Assessment of Alternative Clearances in Interval Management Arrival Operations

NASA Technical Reports Server (NTRS)

Baxley, Brian T.; Wilson, Sara R.; Swieringa, Kurt A.; Johnson, William C.; Roper, Roy D.; Hubbs, Clay E.; Goess, Paul A.; Shay, Richard F.

2016-01-01

Interval Management Alternative Clearances (IMAC) was a human-in-the-loop simulation experiment conducted to explore the Air Traffic Management (ATM) Technology Demonstration (ATD-1) Concept of Operations (ConOps), which combines advanced arrival scheduling, controller decision support tools, and aircraft avionics to enable multiple time deconflicted, efficient arrival streams into a high-density terminal airspace. Interval Management (IM) is designed to support the ATD-1 concept by having an "Ownship" (IM-capable) aircraft achieve or maintain a specific time or distance behind a "Target" (preceding) aircraft. The IM software uses IM clearance information and the Ownship data (route of flight, current location, and wind) entered by the flight crew, and the Target aircraft's Automatic Dependent Surveillance-Broadcast state data, to calculate the airspeed necessary for the IM-equipped aircraft to achieve or maintain the assigned spacing goal.

Recognition, neutralization, and clearance of target peptides in the bloodstream of living mice by molecularly imprinted polymer nanoparticles: a plastic antibody.

PubMed

Hoshino, Yu; Koide, Hiroyuki; Urakami, Takeo; Kanazawa, Hiroaki; Kodama, Takashi; Oku, Naoto; Shea, Kenneth J

2010-05-19

We report that simple, synthetic organic polymer nanoparticles (NPs) can capture and clear a target peptide toxin in the bloodstream of living mice. The protein-sized polymer nanoparticles, with a binding affinity and selectivity comparable to those of natural antibodies, were prepared by combining a functional monomer optimization strategy with molecular-imprinting nanoparticle synthesis. As a result of binding and removal of melittin by NPs in vivo, the mortality and peripheral toxic symptoms due to melittin were significantly diminished. In vivo imaging of the polymer nanoparticles (or "plastic antibodies") established that the NPs accelerate clearance of the peptide from blood and accumulate in the liver. Coupled with their biocompatibility and nontoxic characteristics, plastic antibodies offer the potential for neutralizing a wide range of biomacromolecules in vivo.

30 CFR 18.24 - Electrical clearances.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor...

30 CFR 18.24 - Electrical clearances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor...

30 CFR 18.24 - Electrical clearances.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor...

Application of an in vitro OAT assay in drug design and optimization of renal clearance.

PubMed

Soars, Matthew G; Barton, Patrick; Elkin, Lisa L; Mosure, Kathleen W; Sproston, Joanne L; Riley, Robert J

2014-07-01

1. Optimization of renal clearance is a complex balance between passive and active processes mediated by renal transporters. This work aimed to characterize the interaction of a series of compounds with rat and human organic anion transporters (OATs) and develop quantitative structure-activity relationships (QSARs) to optimize renal clearance. 2. In vitro inhibition assays were established for human OAT1 and rat Oat3 and rat in vivo renal clearance was obtained. Statistically significant quantitative relationships were explored between the compounds' physical properties, their affinity for OAT1 and oat3 and the inter-relationship with unbound renal clearance (URC) in rat. 3. Many of the compounds were actively secreted and in vitro analysis demonstrated that these were ligands for rat and human OAT transporters (IC50 values ranging from <1 to >100 µM). Application of resultant QSAR models reduced renal clearance in the rat from 24 to <0.1 ml/min/kg. Data analysis indicated that the properties associated with increasing affinity at OATs are the same as those associated with reducing URC but orthogonal in nature. 4. This study has demonstrated that OAT inhibition data and QSAR models can be successfully used to optimize rat renal clearance in vivo and provide confidence of translation to humans.

Semen amyloids participate in spermatozoa selection and clearance

PubMed Central

Roan, Nadia R; Sandi-Monroy, Nathallie; Kohgadai, Nargis; Usmani, Shariq M; Hamil, Katherine G; Neidleman, Jason; Montano, Mauricio; Ständker, Ludger; Röcker, Annika; Cavrois, Marielle; Rosen, Jared; Marson, Kara; Smith, James F; Pilcher, Christopher D; Gagsteiger, Friedrich; Sakk, Olena; O’Rand, Michael; Lishko, Polina V; Kirchhoff, Frank

2017-01-01

Unlike other human biological fluids, semen contains multiple types of amyloid fibrils in the absence of disease. These fibrils enhance HIV infection by promoting viral fusion to cellular targets, but their natural function remained unknown. The similarities shared between HIV fusion to host cell and sperm fusion to oocyte led us to examine whether these fibrils promote fertilization. Surprisingly, the fibrils inhibited fertilization by immobilizing sperm. Interestingly, however, this immobilization facilitated uptake and clearance of sperm by macrophages, which are known to infiltrate the female reproductive tract (FRT) following semen exposure. In the presence of semen fibrils, damaged and apoptotic sperm were more rapidly phagocytosed than healthy ones, suggesting that deposition of semen fibrils in the lower FRT facilitates clearance of poor-quality sperm. Our findings suggest that amyloid fibrils in semen may play a role in reproduction by participating in sperm selection and facilitating the rapid removal of sperm antigens. DOI: http://dx.doi.org/10.7554/eLife.24888.001 PMID:28653619

PEGylated Peptide-Based Imaging Agents for Targeted Molecular Imaging.

PubMed

Wu, Huizi; Huang, Jiaguo

2016-01-01

Molecular imaging is able to directly visualize targets and characterize cellular pathways with a high signal/background ratio, which requires a sufficient amount of agents to uptake and accumulate in the imaging area. The design and development of peptide based agents for imaging and diagnosis as a hot and promising research topic that is booming in the field of molecular imaging. To date, selected peptides have been increasingly developed as agents by coupling with different imaging moieties (such as radiometals and fluorophore) with the help of sophisticated chemical techniques. Although a few successes have been achieved, most of them have failed mainly caused by their fast renal clearance and therefore low tumor uptakes, which may limit the effectively tumor retention effect. Besides, several peptide agents based on nanoparticles have also been developed for medical diagnostics. However, a great majority of those agents shown long circulation times and accumulation over time into the reticuloendothelial system (RES; including spleen, liver, lymph nodes and bone marrow) after systematic administration, such long-term severe accumulation probably results in the possible likelihood of toxicity and potentially induces health hazards. Recently reported design criteria have been proposed not only to enhance binding affinity in tumor region with long retention, but also to improve clearance from the body in a reasonable amount of time. PEGylation has been considered as one of the most successful modification methods to prolong tumor retention and improve the pharmacokinetic and pharmacodynamic properties for peptide-based imaging agents. This review summarizes an overview of PEGylated peptides imaging agents based on different imaging moieties including radioisotopes, fluorophores, and nanoparticles. The unique concepts and applications of various PEGylated peptide-based imaging agents are introduced for each of several imaging moieties. Effects of PEGylation on

22 CFR 16.6 - Security clearances.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a fair...

22 CFR 16.6 - Security clearances.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a fair...

22 CFR 16.6 - Security clearances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a fair...

An Analytic Model for the Success Rate of a Robotic Actuator System in Hitting Random Targets.

PubMed

Bradley, Stuart

2015-11-20

Autonomous robotic systems are increasingly being used in a wide range of applications such as precision agriculture, medicine, and the military. These systems have common features which often includes an action by an "actuator" interacting with a target. While simulations and measurements exist for the success rate of hitting targets by some systems, there is a dearth of analytic models which can give insight into, and guidance on optimization, of new robotic systems. The present paper develops a simple model for estimation of the success rate for hitting random targets from a moving platform. The model has two main dimensionless parameters: the ratio of actuator spacing to target diameter; and the ratio of platform distance moved (between actuator "firings") to the target diameter. It is found that regions of parameter space having specified high success are described by simple equations, providing guidance on design. The role of a "cost function" is introduced which, when minimized, provides optimization of design, operating, and risk mitigation costs.

77 FR 75110 - Agency Information Collection Activities: Proposed Collection; Comment Request-Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-19

...: Proposed Collection; Comment Request--Generic Clearance To Conduct Formative Research AGENCY: Food and.... This information collection will conduct research in support of FNS' goal of delivering science-based... target audience, FNS plans to conduct data collections that involve formative research including focus...

E-Reserves Permissions and the Copyright Clearance Center: Process, Efficiency, and Cost

ERIC Educational Resources Information Center

Holobar, J. Christopher; Marshall, Andrew

2011-01-01

This study examines the process of requesting copyright permissions through the Copyright Clearance Center's (CCC) pay-per-use service for electronic course reserves at the Penn State University Libraries in 2008. The authors investigate the efficiency of this process as a function of the percentage of permission requests successfully mediated by…

Evaluation of an Active Clearance Control System Concept

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Lattime, Scott B.; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

2005-01-01

Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance (0.001 in. error).

Evaluation of an Active Clearance Control System Concept

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Lattime, Scott B.; Taylor, Shawn; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

2005-01-01

Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance ( 0.001 in. error).

Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB.

PubMed

Polito, Vinicia A; Li, Hongmei; Martini-Stoica, Heidi; Wang, Baiping; Yang, Li; Xu, Yin; Swartzlander, Daniel B; Palmieri, Michela; di Ronza, Alberto; Lee, Virginia M-Y; Sardiello, Marco; Ballabio, Andrea; Zheng, Hui

2014-09-01

Accumulating evidence implicates impairment of the autophagy-lysosome pathway in Alzheimer's disease (AD). Recently discovered, transcription factor EB (TFEB) is a molecule shown to play central roles in cellular degradative processes. Here we investigate the role of TFEB in AD mouse models. In this study, we demonstrate that TFEB effectively reduces neurofibrillary tangle pathology and rescues behavioral and synaptic deficits and neurodegeneration in the rTg4510 mouse model of tauopathy with no detectable adverse effects when expressed in wild-type mice. TFEB specifically targets hyperphosphorylated and misfolded Tau species present in both soluble and aggregated fractions while leaving normal Tau intact. We provide in vitro evidence that this effect requires lysosomal activity and we identify phosphatase and tensin homolog (PTEN) as a direct target of TFEB that is required for TFEB-dependent aberrant Tau clearance. The specificity and efficacy of TFEB in mediating the clearance of toxic Tau species makes it an attractive therapeutic target for treating diseases of tauopathy including AD. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

48 CFR 945.603-70 - Plant clearance function.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance officer...

48 CFR 945.603-70 - Plant clearance function.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance officer...

Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice.

PubMed

Bhirde, Ashwin A; Patel, Sachin; Sousa, Alioscka A; Patel, Vyomesh; Molinolo, Alfredo A; Ji, Youngmi; Leapman, Richard D; Gutkind, J Silvio; Rusling, James F

2010-12-01

To study the distribution and clearance of polyethylene glycol (PEG)-ylated single-walled carbon nanotube (SWCNTs) as drug delivery vehicles for the anticancer drug cisplatin in mice. PEG layers were attached to SWCNTs and dispersed in aqueous media and characterized using dynamic light scattering, scanning transmission electron microscopy and Raman spectroscopy. Cytotoxicity was assessed in vitro using Annexin-V assay, and the distribution and clearance pathways in mice were studied by histological staining and Raman spectroscopy. Efficacy of PEG-SWCNT-cisplatin for tumor growth inhibition was studied in mice. PEG-SWCNTs were efficiently dispersed in aqueous media compared with controls, and did not induce apoptosis in vitro. Hematoxylin and eosin staining, and Raman bands for SWCNTs in tissues from several vital organs from mice injected intravenously with nanotube bioconjugates revealed that control SWCNTs were lodged in lung tissue as large aggregates compared with the PEG-SWCNTs, which showed little or no accumulation. Characteristic SWCNT Raman bands in feces revealed the presence of bilary or renal excretion routes. Attachment of cisplatin on bioconjugates was visualized with Z-contrast scanning transmission electron microscopy. PEG-SWCNT-cisplatin with the attached targeting ligand EGF successfully inhibited growth of head and neck tumor xenografts in mice. PEG-SWCNTs, as opposed to control SWCNTs, form more highly dispersed delivery vehicles that, when loaded with both cisplatin and EGF, inhibit growth of squamous cell tumors.

48 CFR 801.602-76 - Business clearance review.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or blanket...

48 CFR 801.602-76 - Business clearance review.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or blanket...

30 CFR 18.24 - Electrical clearances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor surfaces, or between uninsulated conductor surfaces and grounded metal surfaces, within the enclosure shall...

30 CFR 18.24 - Electrical clearances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor surfaces, or between uninsulated conductor surfaces and grounded metal surfaces, within the enclosure shall...

45 CFR 675.3 - Medical clearance criteria.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Medical clearance criteria. 675.3 Section 675.3 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION MEDICAL CLEARANCE PROCESS FOR DEPLOYMENT TO ANTARCTICA § 675.3 Medical clearance criteria. (a) The USAP shall...

45 CFR 675.3 - Medical clearance criteria.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Medical clearance criteria. 675.3 Section 675.3 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION MEDICAL CLEARANCE PROCESS FOR DEPLOYMENT TO ANTARCTICA § 675.3 Medical clearance criteria. (a) The USAP shall...

45 CFR 675.3 - Medical clearance criteria.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Medical clearance criteria. 675.3 Section 675.3 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION MEDICAL CLEARANCE PROCESS FOR DEPLOYMENT TO ANTARCTICA § 675.3 Medical clearance criteria. (a) The USAP shall...

24 CFR 3285.305 - Clearance under homes.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

24 CFR 3285.305 - Clearance under homes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

24 CFR 3285.305 - Clearance under homes.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 5 2012-04-01 2012-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

24 CFR 3285.305 - Clearance under homes.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

24 CFR 3285.305 - Clearance under homes.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 5 2013-04-01 2013-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

Tracking short-term biodistribution and long-term clearance of SPIO tracers in magnetic particle imaging

NASA Astrophysics Data System (ADS)

Keselman, Paul; Yu, Elaine Y.; Zhou, Xinyi Y.; Goodwill, Patrick W.; Chandrasekharan, Prashant; Ferguson, R. Matthew; Khandhar, Amit P.; Kemp, Scott J.; Krishnan, Kannan M.; Zheng, Bo; Conolly, Steven M.

2017-05-01

Magnetic particle imaging (MPI) is an emerging tracer-based medical imaging modality that images non-radioactive, kidney-safe superparamagnetic iron oxide (SPIO) tracers. MPI offers quantitative, high-contrast and high-SNR images, so MPI has exceptional promise for applications such as cell tracking, angiography, brain perfusion, cancer detection, traumatic brain injury and pulmonary imaging. In assessing MPI’s utility for applications mentioned above, it is important to be able to assess tracer short-term biodistribution as well as long-term clearance from the body. Here, we describe the biodistribution and clearance for two commonly used tracers in MPI: Ferucarbotran (Meito Sangyo Co., Japan) and LS-oo8 (LodeSpin Labs, Seattle, WA). We successfully demonstrate that 3D MPI is able to quantitatively assess short-term biodistribution, as well as long-term tracking and clearance of these tracers in vivo.

Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein.

PubMed

Park, Daeho; Han, Claudia Z; Elliott, Michael R; Kinchen, Jason M; Trampont, Paul C; Das, Soumita; Collins, Sheila; Lysiak, Jeffrey J; Hoehn, Kyle L; Ravichandran, Kodi S

2011-08-21

Rapid and efficient removal of apoptotic cells by phagocytes is important during development, tissue homeostasis and in immune responses. Efficient clearance depends on the capacity of a single phagocyte to ingest multiple apoptotic cells successively, and to process the corpse-derived cellular material. However, the factors that influence continued clearance by phagocytes are not known. Here we show that the mitochondrial membrane potential of the phagocyte critically controls engulfment capacity, with lower potential enhancing engulfment and vice versa. The mitochondrial membrane protein Ucp2, which acts to lower the mitochondrial membrane potential, was upregulated in phagocytes engulfing apoptotic cells. Loss of Ucp2 reduced phagocytic capacity, whereas Ucp2 overexpression enhanced engulfment. Mutational and pharmacological studies indicated a direct role for Ucp2-mediated mitochondrial function in phagocytosis. Macrophages from Ucp2-deficient mice were impaired in phagocytosis in vitro, and Ucp2-deficient mice showed profound in vivo defects in clearing dying cells in the thymus and testes. Collectively, these data indicate that mitochondrial membrane potential and Ucp2 are key molecular determinants of apoptotic cell clearance. As Ucp2 is linked to metabolic diseases and atherosclerosis, this newly discovered role for Ucp2 in apoptotic cell clearance has implications for the complex aetiology and pathogenesis of these diseases.

46 CFR 56.75-10 - Joint clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be no...

Compressor airfoil tip clearance optimization system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Little, David A.; Pu, Zhengxiang

2015-08-18

A compressor airfoil tip clearance optimization system for reducing a gap between a tip of a compressor airfoil and a radially adjacent component of a turbine engine is disclosed. The turbine engine may include ID and OD flowpath boundaries configured to minimize compressor airfoil tip clearances during turbine engine operation in cooperation with one or more clearance reduction systems that are configured to move the rotor assembly axially to reduce tip clearance. The configurations of the ID and OD flowpath boundaries enhance the effectiveness of the axial movement of the rotor assembly, which includes movement of the ID flowpath boundary.more » During operation of the turbine engine, the rotor assembly may be moved axially to increase the efficiency of the turbine engine.« less

Relationship between rhinosinusitis symptoms and mucociliary clearance time.

PubMed

Boatsman, Justin E; Calhoun, Karen H; Ryan, Matthew W

2006-03-01

To determine the correlation between rhinosinusitis symptoms as assessed by the Sino-Nasal Outcomes Test-20 (SNOT-20) and mucociliary clearance as assessed by the saccharin method. This was a cross-sectional study of 50 adult volunteers. Subjects completed the SNOT-20, and mucociliary clearance was determined with the saccharine method. Correlation coefficients (Spearman's Rho) were calculated for the global SNOT-20 score. The SNOT-20 scores varied from 20 to 54 (mean 30.28) with a possible range of 20 to 100. Clearance times varied from 418 to 2865 seconds (mean 999). There was no significant correlation between global SNOT-20 score and clearance time (r = 0.196). There is no significant correlation between rhinosinusitis symptoms as assessed by SNOT-20 scores and mucociliary clearance. Mucociliary clearance is important for the health of the sinonasal cavities, but clearance time does not appear to be associated with symptom severity in the population studied. A-1b.

Targeting inflammation in pancreatic cancer: Clinical translation

PubMed Central

Steele, Colin William; Kaur Gill, Nina Angharad; Jamieson, Nigel Balfour; Carter, Christopher Ross

2016-01-01

Preclinical modelling studies are beginning to aid development of therapies targeted against key regulators of pancreatic cancer progression. Pancreatic cancer is an aggressive, stromally-rich tumor, from which few people survive. Within the tumor microenvironment cellular and extracellular components exist, shielding tumor cells from immune cell clearance, and chemotherapy, enhancing progression of the disease. The cellular component of this microenvironment consists mainly of stellate cells and inflammatory cells. New findings suggest that manipulation of the cellular component of the tumor microenvironment is possible to promote immune cell killing of tumor cells. Here we explore possible immunogenic therapeutic strategies. Additionally extracellular stromal elements play a key role in protecting tumor cells from chemotherapies targeted at the pancreas. We describe the experimental findings and the pitfalls associated with translation of stromally targeted therapies to clinical trial. Finally, we discuss the key inflammatory signal transducers activated subsequent to driver mutations in oncogenic Kras in pancreatic cancer. We present the preclinical findings that have led to successful early trials of STAT3 inhibitors in pancreatic adenocarcinoma. PMID:27096033

Dynamic clearance measure to evaluate locomotor and perceptuo-motor strategies used for obstacle circumvention in a virtual environment.

PubMed

Darekar, Anuja; Lamontagne, Anouk; Fung, Joyce

2015-04-01

Circumvention around an obstacle entails a dynamic interaction with the obstacle to maintain a safe clearance. We used a novel mathematical interpolation method based on the modified Shepard's method of Inverse Distance Weighting to compute dynamic clearance that reflected this interaction as well as minimal clearance. This proof-of-principle study included seven young healthy, four post-stroke and four healthy age-matched individuals. A virtual environment designed to assess obstacle circumvention was used to administer a locomotor (walking) and a perceptuo-motor (navigation with a joystick) task. In both tasks, participants were asked to navigate towards a target while avoiding collision with a moving obstacle that approached from either head-on, or 30° left or right. Among young individuals, dynamic clearance did not differ significantly between obstacle approach directions in both tasks. Post-stroke individuals maintained larger and smaller dynamic clearance during the locomotor and the perceptuo-motor task respectively as compared to age-matched controls. Dynamic clearance was larger than minimal distance from the obstacle irrespective of the group, task and obstacle approach direction. Also, in contrast to minimal distance, dynamic clearance can respond differently to different avoidance behaviors. Such a measure can be beneficial in contrasting obstacle avoidance behaviors in different populations with mobility problems. Copyright © 2015 Elsevier B.V. All rights reserved.

Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

PubMed

Javid, Ashkan; Zlotnikov, Nataliya; Pětrošová, Helena; Tang, Tian Tian; Zhang, Yang; Bansal, Anil K; Ebady, Rhodaba; Parikh, Maitry; Ahmed, Mijhgan; Sun, Chunxiang; Newbigging, Susan; Kim, Yae Ram; Santana Sosa, Marianna; Glogauer, Michael; Moriarty, Tara J

2016-01-01

Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

Anti-Pseudomonas aeruginosa IgY antibodies augment bacterial clearance in a murine pneumonia model.

PubMed

Thomsen, K; Christophersen, L; Bjarnsholt, T; Jensen, P Ø; Moser, C; Høiby, N

2016-03-01

Oral prophylactic therapy by gargling with pathogen-specific egg yolk immunoglobulins (IgY) may reduce the initial airway colonization with Pseudomonas aeruginosa in cystic fibrosis (CF) patients. IgY antibodies impart passive immunization and we investigated the effects of anti-P. aeruginosa IgY antibodies on bacterial eradication in a murine pneumonia model. P. aeruginosa pneumonia was established in Balb/c mice and the effects of prophylactic IgY administration on lung bacteriology, clinical parameters and subsequent inflammation were compared to controls. Prophylactic administration of IgY antibodies targeting P. aeruginosa significantly reduced the bacterial burden by 2-log 24h post-infection compared to controls and was accompanied by significantly reduced clinical symptom scores and successive inflammatory cytokine profile indicative of diminished lung inflammation. Passive immunization by anti-P. aeruginosa IgY therapy facilitates promptly bacterial clearance and moderates inflammation in P. aeruginosa lung infection and may serve as an adjunct to antibiotics in reducing early colonization. Copyright © 2015. Published by Elsevier B.V.

Carbon Nanotubes in the Human Respiratory Tract-Clearance Modeling.

PubMed

Sturm, Robert

2017-03-01

Clearance of single-wall carbon nanotubes (SWCNT, diameter: 5 nm) and multi-wall carbon nanotubes (MWCNT, diameter: 50 nm) in the respiratory tract was predicted for various age groups (infants, children, adolescents, and adults). The model was founded on the assumption that lung clearance takes place in three distinct phases: (i) fast mucociliary clearance, (ii) slow bronchial clearance, and (iii) alveolar clearance. To each of these phases a specific fraction of deposited particles was attributed, the amount of which depended on particles' geometry and particles' deposition sites in the respiratory system. Clearance velocities were expressed by respective clearance half-times ranging from several hours in the case of fast clearance to tens of days in the case of slow clearance. Results of the simulations clearly demonstrate that for the specific deposition scenario (sitting, nasal breathing) considered here fast clearance fraction exhibits a slight decrease with increasing age, but total clearance times (i.e. time spans, within which 100% of the deposited particulate mass are removed) are rather constant among the age groups. Nanotubes deposited in the respiratory bronchioles and alveoli are usually subject to a long-term storage in these structures and, thus, may trigger malignant transformations in adjacent cells and tissues. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Design of ligand-targeted nanoparticles for enhanced cancer targeting

NASA Astrophysics Data System (ADS)

Stefanick, Jared F.

Ligand-targeted nanoparticles are increasingly used as drug delivery vehicles for cancer therapy, yet have not consistently produced successful clinical outcomes. Although these inconsistencies may arise from differences in disease models and target receptors, nanoparticle design parameters can significantly influence therapeutic efficacy. By employing a multifaceted synthetic strategy to prepare peptide-targeted nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities, this work evaluates the roles of polyethylene glycol (PEG) coating, ethylene glycol (EG) peptide-linker length, peptide hydrophilicity, peptide density, and nanoparticle size on tumor targeting in a systematic manner. These parameters were analyzed in multiple disease models by targeting human epidermal growth factor receptor 2 (HER2) in breast cancer and very late antigen-4 (VLA-4) in multiple myeloma to demonstrate the widespread applicability of this approach. By increasing the hydrophilicity of the targeting peptide sequence and simultaneously optimizing the EG peptide-linker length, the in vitro cellular uptake of targeted liposomes was significantly enhanced. Specifically, including a short oligolysine chain adjacent to the targeting peptide sequence effectively increased cellular uptake ~80-fold using an EG6 peptide-linker compared to ~10-fold using an EG45 linker. In vivo, targeted liposomes prepared in a traditional manner lacking the oligolysine chain demonstrated similar biodistribution and tumor uptake to non-targeted liposomes. However, by including the oligolysine chain, targeted liposomes using an EG45 linker significantly improved tumor uptake ~8-fold over non-targeted liposomes, while the use of an EG6 linker decreased tumor accumulation and uptake, owing to differences in cellular uptake kinetics, clearance mechanisms, and binding site barrier effects. To further improve tumor targeting and enhance the selectivity of targeted

Sustainability of a Targeted Intervention Package: First Step to Success in Oregon

ERIC Educational Resources Information Center

Loman, Sheldon L.; Rodriguez, Billie Jo; Horner, Robert H.

2010-01-01

Variables affecting the sustained implementation of evidence-based practices are receiving increased attention. A descriptive analysis of the variables associated with sustained implementation of First Step to Success (FSS), a targeted intervention for young students at risk for behavior disorders, is provided. Measures based on a conceptual model…

Targeted and Controlled Anticancer Drug Delivery and Release with Magnetoelectric Nanoparticles

NASA Astrophysics Data System (ADS)

Rodzinski, Alexandra

A major challenge of cancer treatment is successful discrimination of cancer cells from healthy cells. Nanotechnology offers multiple venues for efficient cancer targeting. Magnetoelectric nanoparticles (MENs) are a novel, multifaceted, physics-based cancer treatment platform that enables high specificity cancer targeting and externally controlled loaded drug release. The unique magnetoelectric coupling of MENs allows them to convert externally applied magnetic fields into intrinsic electric signals, which allows MENs to both be drawn magnetically towards the cancer site and to electrically interface with cancer cells. Once internalized, the MEN payload release can be externally triggered with a magnetic field. MENs uniquely allow for discrete manipulation of the drug delivery and drug release mechanisms to allow an unprecedented level of control in cancer targeting. In this study, we demonstrate the physics behind the MEN drug delivery platform, test the MEN drug delivery platform for the first time in a humanized mouse model of cancer, and characterize the biodistribution and clearance of MENs. We found that MENs were able to fully cure the model cancer, which in this case was human ovarian carcinoma treated with paclitaxel. When compared to conventional magnetic nanoparticles and FDA approved organic PLGA nanoparticles, MENs are the highest performing treatment, even in the absence of peripheral active targeting molecules. We also mapped the movement through peripheral organs and established clearance trends of the MENs. The MENs cancer treatment platform has immense potential for future medicine, as it is generalizable, personalizable, and readily traceable in the context of treating essentially any type of cancer.

A model of clearance rate regulation in mussels

NASA Astrophysics Data System (ADS)

Fréchette, Marcel

2012-10-01

Clearance rate regulation has been modelled as an instantaneous response to food availability, independent of the internal state of the animals. This view is incompatible with latent effects during ontogeny and phenotypic flexibility in clearance rate. Internal-state regulation of clearance rate is required to account for these patterns. Here I develop a model of internal-state based regulation of clearance rate. External factors such as suspended sediments are included in the model. To assess the relative merits of instantaneous regulation and internal-state regulation, I modelled blue mussel clearance rate and growth using a DEB model. In the usual standard feeding module, feeding is governed by a Holling's Type II response to food concentration. In the internal-state feeding module, gill ciliary activity and thus clearance rate are driven by internal reserve level. Factors such as suspended sediments were not included in the simulations. The two feeding modules were compared on the basis of their ability to capture the impact of latent effects, of environmental heterogeneity in food abundance and of physiological flexibility on clearance rate and individual growth. The Holling feeding module was unable to capture the effect of any of these sources of variability. In contrast, the internal-state feeding module did so without any modification or ad hoc calibration. Latent effects, however, appeared transient. With simple annual variability in temperature and food concentration, the relationship between clearance rate and food availability predicted by the internal-state feeding module was quite similar to that observed in Norwegian fjords. I conclude that in contrast with the usual Holling feeding module, internal-state regulation of clearance rate is consistent with well-documented growth and clearance rate patterns.

Study of blade clearance effects on centrifugal pumps

NASA Technical Reports Server (NTRS)

Hoshide, R. K.; Nielson, C. E.

1972-01-01

A program of analysis, design, fabrication, and testing has been conducted to develop and experimentally verify analytical models to predict the effects of impeller blade clearance on centrifugal pumps. The effect of tip clearance on pump efficiency, and the relationship between the head coefficient and torque loss with tip clearance was established. Analysis were performed to determine the cost variation in design, manufacture, and test that would occur between unshrouded and shrouded impellers. An impeller, representative of typical rocket engine impellers, was modified by removing its front shroud to permit variation of its blade clearances. It was tested in water with special instrumentation to provide measurements of blade surface pressures during operation. Pump performance data were obtained from tests at various impeller tip clearances. Blade pressure data were obtained at the nominal tip clearance. Comparisons of predicted and measured data are given.

Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both β-amyloid production and clearance.

PubMed

Zhu, Zhiyuan; Yan, Jianming; Jiang, Wei; Yao, Xin-gang; Chen, Jing; Chen, Lili; Li, Chenjing; Hu, Lihong; Jiang, Hualiang; Shen, Xu

2013-08-07

Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The β-amyloid (Aβ)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and Aβ production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aβ production by suppressing β-site amyloid precursor protein cleavage enzyme 1 expression and promote Aβ clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased Aβ formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.

48 CFR 245.602-70 - Plant clearance procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

48 CFR 245.602-70 - Plant clearance procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

48 CFR 245.602-70 - Plant clearance procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

48 CFR 245.602-70 - Plant clearance procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

Effect of neurotrauma on hepatic drug clearance.

PubMed

Boucher, B A; Kuhl, D A; Fabian, T C; Robertson, J T

1991-11-01

Lorazepam, antipyrine, and indocyanine green were administered to 10 patients with severe head injuries as marker substrates of hepatic glucuronidation, oxidation, and hepatic blood flow, respectively. Pharmacokinetic parameter estimates were determined at baseline (20 to 80 hours after injury) and up to three additional times thereafter (study days 4, 7, and 14). Antipyrine clearance was increased significantly from baseline (0.50 +/- 0.31 ml/min/kg) on study days 4, 7, and 14 (p less than 0.0001). Increases in antipyrine clearance from baseline to the last study day were observed in all study patients ranging from 14% to 207%. A significant increase was also observed in lorazepam clearance on study day 14 relative to baseline (1.39 +/- 0.56 ml/min/kg) (p less than 0.005). Increases in lorazepam clearance occurred in seven of nine patients over time ranging from 9% to 130%. The unbound fraction of lorazepam did not change significantly over the study period. Likewise, no significant change was observed in the clearance of indocyanine green over time. Antipyrine clearance and alpha 1-acid glycoprotein (r = 0.41), and lorazepam clearance and C-reactive protein (r = -0.38) were significantly correlated (p less than 0.05). Similarly, antipyrine and lorazepam clearances were significantly correlated with injury severity based on the Acute Physiologic and Chronic Health Evaluation (APACHE II) score (r = -0.43 and r = -0.37, respectively). These findings suggest that hepatic oxidative and conjugative metabolism increase significantly over time in patients after acute head injury. An awareness of the potential for pharmacokinetic alterations in similarly metabolized drugs used for patients with severe head injuries is recommended.

Targeting Nrf2 Signaling Improves Bacterial Clearance by Alveolar Macrophages in Patients with COPD and in a Mouse Model

PubMed Central

Harvey, Christopher J.; Thimmulappa, Rajesh K.; Sethi, Sanjay; Kong, Xiaoni; Yarmus, Lonny; Brown, Robert H.; David, Feller-Kopman; Wise, Robert; Biswal, Shyam

2016-01-01

Patients with chronic obstructive pulmonary disease (COPD) have innate immune dysfunction in the lung largely due to defective macrophage phagocytosis. This deficiency results in periodic bacterial infections that cause acute exacerbations of COPD, a major source of morbidity and mortality. Recent studies indicate that a decrease in Nrf2 (nuclear erythroid–related factor 2) signaling in patients with COPD may hamper their ability to defend against oxidative stress, although the role of Nrf2 in COPD exacerbations has not been determined. Here, we test whether activation of Nrf2 by the phytochemical sulforaphane restores phagocytosis of clinical isolates of nontypeable Haemophilus influenza (NTHI) and Pseudomonas aeruginosa (PA) by alveolar macrophages from patients with COPD. Sulforaphane treatment restored bacteria recognition and phagocytosis in alveolar macrophages from COPD patients. Furthermore, sulforaphane treatment enhanced pulmonary bacterial clearance by alveolar macrophages and reduced inflammation in wild-typemice but not in Nrf2-deficientmice exposed to cigarette smoke for 6 months. Gene expression and promoter analysis revealed that Nrf2 increased phagocytic ability of macrophages by direct transcriptional up-regulation of the scavenger receptor MARCO. Disruption of Nrf2 or MARCO abrogated sulforaphane-mediated bacterial phagocytosis by COPD alveolar macrophages. Our findings demonstrate the importance of Nrf2 and its downstream target MARCO in improving antibacterial defenses and provide a rationale for targeting this pathway, via pharmacological agents such as sulforaphane, to prevent exacerbations of COPD caused by bacterial infection. PMID:21490276

Clearance of yellow tattoo ink with a novel 532-nm picosecond laser.

PubMed

Alabdulrazzaq, Hamad; Brauer, Jeremy A; Bae, Yoon-Soo; Geronemus, Roy G

2015-04-01

Although technology and tattoo removal methods continue to evolve, yellow pigment clearance continues to be challenging and usually unsuccessful. We describe a case series of six tattoos containing yellow ink, successfully treated with a frequency-doubled Nd:YAG 532-nm picosecond laser. Case series with six subjects participating for the treatment of multicolored tattoos that contain yellow pigment. Treatments performed with a frequency-doubled Nd:YAG 532-nm picosecond laser at 6-8 week intervals. One subject achieved complete clearance of the treated site after one session, and five subjects required 2-4 treatments to achieve over 75% clearance. Minimal downtime was experienced, and no scarring or textural skin changes were observed in any of the treated sites. This is the first case series that demonstrates effective and consistent reduction of yellow tattoo ink using a frequency doubled Nd:YAG 532-nm laser with a picosecond pulse duration. Treatments were well tolerated and subjects had positive outcomes. This is a small observational case series from an ongoing clinical trial, and studies with a larger sample size and comparative group are needed in the future. © 2015 Wiley Periodicals, Inc.

Predicting Human Clearance of OATP substrates using Cynomolgus monkey: In vitro-in vivo scaling of hepatic uptake clearance.

PubMed

de Bruyn, Tom; Ufuk, Ayse; Cantrill, Carina; Kosa, Rachel E; Bi, Yi-An; Niosi, Mark; Modi, Sweta; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena Vs; Galetin, Aleksandra; Houston, J Brian

2018-05-02

This work explores the utility of the cynomolgus monkey as a preclinical model to predict hepatic uptake clearance mediated by organic anion transporting polypeptide (OATP) transporters. Nine OATP substrates (rosuvastatin, pravastatin, repaglinide, fexofenadine, cerivastatin, telmisartan, pitavastatin, bosentan and valsartan) were investigated in plated cynomolgus monkey and human hepatocytes. Total uptake clearance and passive diffusion were measured in vitro from initial rates in the absence and presence of the OATP inhibitor rifamycin SV, respectively. Total uptake clearance values in plated hepatocytes ranged over three orders of magnitude in both species with a similar rank order and good agreement in the relative contribution of active transport to total uptake between cynomolgus monkey and human. In vivo hepatic clearance for these nine drugs was determined in cynomolgus monkey after intravenous dosing. Hepatic clearances showed a similar range to human parameters and good predictions from respective hepatocyte parameters (with 2.7 and 3.8-fold bias on average, respectively). The use of cross species empirical scaling factors (based on either dataset average or individual drug scaling factor from cynomolgus monkey data) improved prediction (less bias, better concordance) of human hepatic clearance from human hepatocyte data alone. In vitro intracellular binding in hepatocytes also correlated well between species. It is concluded that the minimal species differences observed for the current dataset between cynomolgus monkey and human hepatocyte uptake, both in vitro and in vivo, support future use of this preclinical model to delineate drug hepatic uptake and enable prediction of human in vivo intrinsic hepatic clearance. The American Society for Pharmacology and Experimental Therapeutics.

Simple sampling strategy for measuring inulin renal clearance.

PubMed

Horio, Masaru; Imai, Enyu; Yasuda, Yoshinari; Hishida, Akira; Matsuo, Seiichi

2009-02-01

In the standard method of inulin clearance (Cin), three sets of serum and urine samples are collected during a 2-hour clearance period. For a practical use of this method, sampling should be the minimal number allowable while still providing enough accuracy. The aim of this study was to evaluate the validity of inulin renal clearance with assumed single urine collection with a period such as 30, 60 or 90 minutes. Inulin clearance data collected by the standard method from 737 individuals were used. Changes of serum inulin concentrations between 45 and 105 minutes after the start of the infusion were analyzed. We used first urine collection to calculate the inulin clearance with single urine collection (Cin-30 min). We assumed single urine collection for 60 or 90 minutes by combining the urine data of the consecutive 30-minute periods. Inulin clearances (Cin-60 min, Cin-90 min) were calculated from the assumed single urine collections, respectively. Serum inulin concentration did not reach equilibrium during the clearance period. It increased in subjects with low glomerular filtration rate (GFR) and decreased in subjects with normal GFR. The amount of the change was small and -0.5 +/- 12.6% in subjects with GFR over 30 ml/min per 1.73 m(2). Cin-30 min, Cin-60 min and Cin-90 min showed high correlation coefficients against Cin-ST (0.962, 0.988 and 0.998, respectively). Systemic biases in these clearances were negligible (under 1 ml/min per 1.73 m(2)). Root mean square error (RMSE) were 10.4, 5.3 and 2.3 ml/min per 1.73 m(2) for Cin-30 min, Cin-60 min and Cin-90 min, respectively. These data indicated that accuracy of inulin clearance depends on the duration of the urine collection period. Inulin clearance with a single urine collection is a convenient method. We showed that single urine collection for 30 minutes or a longer period has reasonable accuracy in calculation of inulin clearance. We propose a method of inulin clearance with single urine collection for 60

78 FR 77027 - Overhead Clearance (Air-Draft) Accidents

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

... No. USCG-2013-0466] Overhead Clearance (Air-Draft) Accidents AGENCY: Coast Guard, DHS. ACTION... clearance (air-draft) accidents. In its petition, which calls for vessel masters to be provided with accurate vertical air draft information, a maritime organization has described 16 overhead clearance...

Confusion in Using Pre-Departure Clearances

DOT National Transportation Integrated Search

1996-12-20

In 1990, the FAA implemented the Pre-Departure Clearance (PDC) program at a : number of U.S. airports. This system allows pilots to obtain IFR clearances : through aircraft ACARS units prior to taxi-out, thus eliminating the need for : verbal communi...

Aerial Refueling Clearance Initiation Request

DTIC Science & Technology

2016-07-14

and receiver agencies. The AR Clearance Initiation Request document recognizes the requirement for definitive aerial refueling agreements between...and contractual tanker support requests from one organization or nation to another. The AR Clearance Initiation Request document is not intended to...proprietary, sensitive, classified or otherwise restricted information. ARSAG documents, as prepared, are not DOD, MOD or NATO standards, but provide

48 CFR 945.670-1 - Plant clearance function.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the...

48 CFR 945.670-1 - Plant clearance function.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the...

Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring.

PubMed

Vassal, G; Michel, G; Espérou, H; Gentet, J C; Valteau-Couanet, D; Doz, F; Mechinaud, F; Galambrun, C; Neven, B; Zouabi, H; Nguyen, L; Puozzo, C

2008-01-01

Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability. A new intravenous (IV) dosing of busulfan (Bu) based on body weight, designed to improve AUC targeting without TDM and dose-adjustment, was prospectively evaluated. Bu was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for <9 kg; 1.2 mg/kg for 9 to <16 kg; 1.1 mg/kg for 16-23 kg; 0.95 mg/kg for >23-34 kg; 0.80 mg/kg for >34 kg. Bu treatment was followed by Cyclophosphamide or Melphalan prior to allogeneic or autologous transplantation in 55 children aged 0.3-17.2 years (median 5.6 years). No difference in AUC values was observed between weight strata (mean +/- SD 1248 +/- 205 micromol.min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900-1500 micromol.min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window.

AHERA CLEARANCE AT TWENTY ABATEMENT SITES

EPA Science Inventory

A study was conducted during the summer of 1988 to document Asbestos Hazard Emergency Response Act (AHERA) clearance air-sampling practices and clearance concentrations of airborne asbestos at 20 asbestos-abatement sites in New Jersey. Each abatement took place in a school buildi...

AHERA CLEARANCE AT TWENTY ABATEMENT SITES

EPA Science Inventory

A study was conducted during the summer of 1988 to document Asbestos Hazard Emergency Response Act (AHERA) clearance air sampling practices and clearance concentrations of airborne asbestos at 20 asbestos-abatement sites in New Jersey. ach abatement took place in a school buildin...

Shear joint capability versus bolt clearance

NASA Technical Reports Server (NTRS)

Lee, H. M.

1992-01-01

The results of a conservative analysis approach into the determination of shear joint strength capability for typical space-flight hardware as a function of the bolt-hole clearance specified in the design are presented. These joints are comprised of high-strength steel fasteners and abutments constructed of aluminum alloys familiar to the aerospace industry. A general analytical expression was first arrived at which relates bolt-hole clearance to the bolt shear load required to place all joint fasteners into a shear transferring position. Extension of this work allowed the analytical development of joint load capability as a function of the number of fasteners, shear strength of the bolt, bolt-hole clearance, and the desired factor of safety. Analysis results clearly indicate that a typical space-flight hardware joint can withstand significant loading when less than ideal bolt hole clearances are used in the design.

Fuel conservation through active control of rotor clearances

NASA Technical Reports Server (NTRS)

Beitler, R. S.; Saunders, A. A.; Wanger, R. P.

1980-01-01

Under the NASA-sponsored Energy Efficient Engine (EEE) Project, technology is being developed which will significantly reduce the fuel consumption of turbofan engines for subsonic transport aircraft. One technology concept being pursued is active control of rotor tip clearances. Attention is given to rotor tip clearance considerations and an overview of preliminary study results as well as the General Electric EEE clearance control approach is presented. Finally, potential fuel savings with active control of rotor clearances for a typical EEE mission are predicted.

15 CFR 752.15 - Export clearance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Export clearance. 752.15 Section 752... OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS SPECIAL COMPREHENSIVE LICENSE § 752.15 Export clearance. (a) Shipper's Export Declaration (SED) or Automated Export...

ADAPTIVE CLEARANCE CONTROL SYSTEMS FOR TURBINE ENGINES

NASA Technical Reports Server (NTRS)

Blackwell, Keith M.

2004-01-01

The Controls and Dynamics Technology Branch at NASA Glenn Research Center primarily deals in developing controls, dynamic models, and health management technologies for air and space propulsion systems. During the summer of 2004 I was granted the privilege of working alongside professionals who were developing an active clearance control system for commercial jet engines. Clearance, the gap between the turbine blade tip and the encompassing shroud, increases as a result of wear mechanisms and rubbing of the turbine blades on shroud. Increases in clearance cause larger specific fuel consumption (SFC) and loss of efficient air flow. This occurs because, as clearances increase, the engine must run hotter and bum more fuel to achieve the same thrust. In order to maintain efficiency, reduce fuel bum, and reduce exhaust gas temperature (EGT), the clearance must be accurately controlled to gap sizes no greater than a few hundredths of an inch. To address this problem, NASA Glenn researchers have developed a basic control system with actuators and sensors on each section of the shroud. Instead of having a large uniform metal casing, there would be sections of the shroud with individual sensors attached internally that would move slightly to reform and maintain clearance. The proposed method would ultimately save the airline industry millions of dollars.

14 CFR 1260.63 - Customs clearance and visas.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For...

14 CFR 1260.63 - Customs clearance and visas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For...

14 CFR 1260.63 - Customs clearance and visas.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For...

14 CFR 1260.63 - Customs clearance and visas.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For...

Parietal lobe critically supports successful paired immediate and single-item delayed memory for targets.

PubMed

Krumm, Sabine; Kivisaari, Sasa L; Monsch, Andreas U; Reinhardt, Julia; Ulmer, Stephan; Stippich, Christoph; Kressig, Reto W; Taylor, Kirsten I

2017-05-01

The parietal lobe is important for successful recognition memory, but its role is not yet fully understood. We investigated the parietal lobes' contribution to immediate paired-associate memory and delayed item-recognition memory separately for hits (targets) and correct rejections (distractors). We compared the behavioral performance of 56 patients with known parietal and medial temporal lobe dysfunction (i.e. early Alzheimer's Disease) to 56 healthy control participants in an immediate paired and delayed single item object memory task. Additionally, we performed voxel-based morphometry analyses to investigate the functional-neuroanatomic relationships between performance and voxel-based estimates of atrophy in whole-brain analyses. Behaviorally, all participants performed better identifying targets than rejecting distractors. The voxel-based morphometry analyses associated atrophy in the right ventral parietal cortex with fewer correct responses to familiar items (i.e. hits) in the immediate and delayed conditions. Additionally, medial temporal lobe integrity correlated with better performance in rejecting distractors, but not in identifying targets, in the immediate paired-associate task. Our findings suggest that the parietal lobe critically supports successful immediate and delayed target recognition memory, and that the ventral aspect of the parietal cortex and the medial temporal lobe may have complementary preferences for identifying targets and rejecting distractors, respectively, during recognition memory. Copyright © 2017. Published by Elsevier Inc.

Age-Related Decline in Brain and Hepatic Clearance of Amyloid-Beta is Rectified by the Cholinesterase Inhibitors Donepezil and Rivastigmine in Rats.

PubMed

Mohamed, Loqman A; Qosa, Hisham; Kaddoumi, Amal

2015-05-20

In Alzheimer's disease (AD), accumulation of brain amyloid-β (Aβ) depends on imbalance between production and clearance of Aβ. Several pathways for Aβ clearance have been reported including transport across the blood-brain barrier (BBB) and hepatic clearance. The incidence of AD increases with age and failure of Aβ clearance correlates with AD. The cholinesterase inhibitors (ChEIs) donepezil and rivastigmine are used to ease the symptoms of dementia associated with AD. Besides, both drugs have been reported to provide neuroprotective and disease-modifying effects. Here, we investigated the effect of ChEIs on age-related reduced Aβ clearance. Findings from in vitro and in vivo studies demonstrated donepezil and rivastigmine to enhance (125)I-Aβ40 clearance. Also, the increase in brain and hepatic clearance of (125)I-Aβ40 was more pronounced in aged compared to young rats, and was associated with significant reduction in brain Aβ endogenous levels determined by ELISA. Furthermore, the enhanced clearance was concomitant with up-regulation in the expression of Aβ major transport proteins P-glycoprotein and LRP1. Collectively, our findings that donepezil and rivastigmine enhance Aβ clearance across the BBB and liver are novel and introduce an additional mechanism by which both drugs could affect AD pathology. Thus, optimizing their clinical use could help future drug development by providing new drug targets and possible mechanisms involved in AD pathology.

19 CFR 122.77 - Clearance certificate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart; Electronic...

Latency reversal and viral clearance to cure HIV-1

PubMed Central

Margolis, David M.; Garcia, J. Victor; Hazuda, Daria J.; Haynes, Barton F.

2016-01-01

Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication—a cure for AIDS. Paired testing of latency reversal and clearance strategies has begun, but additional obstacles to HIV eradication may emerge. Nevertheless, there is reason for optimism that advances in long-acting antiretroviral therapy and HIV prevention strategies will contribute to efforts in HIV cure research and that the implementation of these efforts will synergize to markedly blunt the effect of the HIV pandemic on society. PMID:27463679

Integrated Turbine Tip Clearance and Gas Turbine Engine Simulation

NASA Technical Reports Server (NTRS)

Chapman, Jeffryes W.; Kratz, Jonathan; Guo, Ten-Huei; Litt, Jonathan

2016-01-01

Gas turbine compressor and turbine blade tip clearance (i.e., the radial distance between the blade tip of an axial compressor or turbine and the containment structure) is a major contributing factor to gas path sealing, and can significantly affect engine efficiency and operational temperature. This paper details the creation of a generic but realistic high pressure turbine tip clearance model that may be used to facilitate active tip clearance control system research. This model uses a first principles approach to approximate thermal and mechanical deformations of the turbine system, taking into account the rotor, shroud, and blade tip components. Validation of the tip clearance model shows that the results are realistic and reflect values found in literature. In addition, this model has been integrated with a gas turbine engine simulation, creating a platform to explore engine performance as tip clearance is adjusted. Results from the integrated model explore the effects of tip clearance on engine operation and highlight advantages of tip clearance management.

Rotating coherent flow structures as a source for narrowband tip clearance noise from axial fans

NASA Astrophysics Data System (ADS)

Zhu, Tao; Lallier-Daniels, Dominic; Sanjosé, Marlène; Moreau, Stéphane; Carolus, Thomas

2018-03-01

Noise from axial fans typically increases significantly as the tip clearance is increased. In addition to the broadband tip clearance noise at the design flow rate, narrowband humps also associated with the tip flow are observed in the far-field acoustic spectra at lower flow rate. In this study, both experimental and numerical methods are used to shed more light on the noise generation mechanism of this narrowband tip clearance noise and provide a unified description of this source. Unsteady aeroacoustic predictions with the Lattice-Boltzmann Method (LBM) are successfully compared with experiment. Such a validation allows using LBM data to conduct a detailed modal analysis of the pressure field for detecting rotating coherent flow structures which might be considered as noise sources. As previously found in ring fans the narrowband humps in the far-field noise spectra are found to be related to the tip clearance noise that is generated by an interaction of coherent flow structures present in the tip region with the leading edge of the impeller blades. The visualization of the coherent structures shows that they are indeed part of the unsteady tip clearance vortex structures. They are hidden in a complex, spatially and temporally inhomogeneous flow field, but can be recovered by means of appropriate filtering techniques. Their pressure trace corresponds to the so-called rotational instability identified in previous turbomachinery studies, which brings a unified picture of this tip-noise phenomenon for the first time.

CF6 High Pressure Compressor and Turbine Clearance Evaluations

NASA Technical Reports Server (NTRS)

Radomski, M. A.; Cline, L. D.

1981-01-01

In the CF6 Jet Engine Diagnostics Program the causes of performance degradation were determined for each component of revenue service engines. It was found that a significant contribution to performance degradation was caused by increased airfoil tip radial clearances in the high pressure compressor and turbine areas. Since the influence of these clearances on engine performance and fuel consumption is significant, it is important to accurately establish these relatonships. It is equally important to understand the causes of clearance deterioration so that they can be reduced or eliminated. The results of factory engine tests run to enhance the understanding of the high pressure compressor and turbine clearance effects on performance are described. The causes of clearance deterioration are indicated and potential improvements in clearance control are discussed.

Time-of-Flight Tip-Clearance Measurements

NASA Technical Reports Server (NTRS)

Dhadwal, H. S.; Kurkov, A. P.; Janetzke, D. C.

1999-01-01

In this paper a time-of-flight probe system incorporating the two integrated fiber optic probes which are tilted equally relative to the probe holder centerline, is applied for the first time to measure the tip clearance of an advanced fan prototype. Tip clearance is largely independent of the signal amplitude and it relies on timing measurement. This work exposes optical effects associated with the fan blade stagger angle that were absent during the original spin-rig experiment on the zero stagger rotor. Individual blade tip clearances were measured with accuracy of +/- 127-mm (+/- 0.005-in). Probe features are discussed and improvements to the design are suggested.

Comparison of Two Alternate Methods for Tracking Toe Clearance

NASA Technical Reports Server (NTRS)

Miller, Christopher A.; Feiveson, Alan H.; Bloomberg, Jacob J.

2007-01-01

Analyses of toe clearance during the swing phase of locomotion has often been utilized in determining a subject s propensity to trip while either walking or stepping over an obstacle. In the literature, toe clearance has been studied using a marker on the superior aspect of the second toe (rtoe), a marker on the lateral aspect of the fifth metatarsal head (mth5), or a virtual marker positioned at the anterior tip of the toe (vtoe). The purpose of this study was to compute toe clearance and associated parameters using a fifth metatarsal marker and a virtual toe marker, and compare the results with those of the standard toe marker. Subjects walked on a motorized treadmill at five different speeds while performing a visual acuity task at two separate target distances (ten 60-second trials). The minimum vertical height (TCl) was determined for each stride, along with its point of occurence in the gait cycle, and the angles of the foot and ankle at that time. A regression analysis was performed on the vtoe and mth5 results versus rtoe individually. For all TCl parameters, the mth5 marker did not correlate well with rtoe; the vtoe marker showed better agreement. Most importantly, the mth5 marker predicted a later occurence of TCl than rtoe and vtoe - thereby missing the most dangerous point in swing phase for a trip. From this analysis, the vtoe marker proved to be a better analog to rtoe than mth5, especially for determining a subject s propensity to trip.

Differences in amyloid-β clearance across mouse and human blood-brain barrier models: kinetic analysis and mechanistic modeling.

PubMed

Qosa, Hisham; Abuasal, Bilal S; Romero, Ignacio A; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N; Kaddoumi, Amal

2014-04-01

Alzheimer's disease (AD) has a characteristic hallmark of amyloid-β (Aβ) accumulation in the brain. This accumulation of Aβ has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate Aβ clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient Aβ clearance. However, the contribution of each process to Aβ clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect Aβ clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to Aβ clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected (125)I-Aβ40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare Aβ clearance between mouse and human BBB models. Kinetic studies for Aβ40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of (125)I-Aβ40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of (125)I-Aβ40 and the rate of each process. Established mechanistic model suggested significantly higher rates of Aβ uptake and degradation in bEnd3 cells as rationale for the observed differences in (125)I-Aβ40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of Aβ from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to Aβ clearance and offer, for the first time, a mathematical model that describes

Differences in amyloid-β clearance across mouse and human blood-brain barrier models: Kinetic analysis and mechanistic modeling

PubMed Central

Qosa, Hisham; Abuasal, Bilal S.; Romero, Ignacio A.; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N.; Kaddoumi, Amal

2014-01-01

Alzheimer’s disease (AD) has a characteristic hallmark of amyloid-β (Aβ) accumulation in the brain. This accumulation of Aβ has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate Aβ clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient Aβ clearance. However, the contribution of each process to Aβ clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect Aβ clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to Aβ clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected 125I-Aβ40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare Aβ clearance between mouse and human BBB models. Kinetic studies for Aβ40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of 125I-Aβ40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of 125I-Aβ40 and the rate of each process. Established mechanistic model suggested significantly higher rates of Aβ uptake and degradation in bEnd3 cells as rationale for the observed differences in 125I-Aβ40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of Aβ from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to Aβ clearance and offer, for the first time, a mathematical model that describes A�

Clearance systems in the brain-implications for Alzheimer disease.

PubMed

Tarasoff-Conway, Jenna M; Carare, Roxana O; Osorio, Ricardo S; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J

2015-08-01

Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.

Clearance systems in the brain—implications for Alzheimer disease

PubMed Central

Tarasoff-Conway, Jenna M.; Carare, Roxana O.; Osorio, Ricardo S.; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V.; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J.

2015-01-01

Accumulation of toxic protein aggregates—amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood–brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ. PMID:26195256

Radioaerosol lung clearance in patients with active pulmonary sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobs, M.P.; Baughman, R.P.; Hughes, J.

1985-05-01

Pulmonary radioaerosol clearance rate of /sup 99m/Tc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with /sup 67/Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (includingmore » 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).« less

Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems

PubMed Central

Kydd, Janel; Jadia, Rahul; Velpurisiva, Praveena; Gad, Aniket; Paliwal, Shailee; Rai, Prakash

2017-01-01

Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil® in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as ‘vascular targeting’), the tumor microenvironment (‘tissue targeting’) or the individual cancer cells (‘cellular targeting’). Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines. PMID:29036899

Intelligent Engine Systems: HPT Clearance Control

NASA Technical Reports Server (NTRS)

2008-01-01

The Advanced Thermally Actuated Clearance Control System underwent several studies. Improved flow path isolation quantified what can be gained by making the HPT case nearly adiabatic. The best method of heat transfer was established, and finally two different borrowed air cooling circuits were evaluated to be used for the HPT Active Clearance Control System.

Mitochondria-targeted ubiquinone (MitoQ) enhances acetaldehyde clearance by reversing alcohol-induced posttranslational modification of aldehyde dehydrogenase 2: A molecular mechanism of protection against alcoholic liver disease.

PubMed

Hao, Liuyi; Sun, Qian; Zhong, Wei; Zhang, Wenliang; Sun, Xinguo; Zhou, Zhanxiang

2018-04-01

Alcohol metabolism in the liver generates highly toxic acetaldehyde. Breakdown of acetaldehyde by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria consumes NAD + and generates reactive oxygen/nitrogen species, which represents a fundamental mechanism in the pathogenesis of alcoholic liver disease (ALD). A mitochondria-targeted lipophilic ubiquinone (MitoQ) has been shown to confer greater protection against oxidative damage in the mitochondria compared to untargeted antioxidants. The present study aimed to investigate if MitoQ could preserve mitochondrial ALDH2 activity and speed up acetaldehyde clearance, thereby protects against ALD. Male C57BL/6J mice were exposed to alcohol for 8 weeks with MitoQ supplementation (5mg/kg/d) for the last 4 weeks. MitoQ ameliorated alcohol-induced oxidative/nitrosative stress and glutathione deficiency. It also reversed alcohol-reduced hepatic ALDH activity and accelerated acetaldehyde clearance through modulating ALDH2 cysteine S-nitrosylation, tyrosine nitration and 4-hydroxynonenol adducts formation. MitoQ ameliorated nitric oxide (NO) donor-mediated ADLH2 S-nitrosylation and nitration in Hepa-1c1c7 cells under glutathion depletion condition. In addition, alcohol-increased circulating acetaldehyde levels were accompanied by reduced intestinal ALDH activity and impaired intestinal barrier. In accordance, MitoQ reversed alcohol-increased plasma endotoxin levels and hepatic toll-like receptor 4 (TLR4)-NF-κB signaling along with subsequent inhibition of inflammatory cell infiltration. MitoQ also reversed alcohol-induced hepatic lipid accumulation through enhancing fatty acid β-oxidation. Alcohol-induced ER stress and apoptotic cell death signaling were reversed by MitoQ. This study demonstrated that speeding up acetaldehyde clearance by preserving ALDH2 activity critically mediates the beneficial effect of MitoQ on alcohol-induced pathogenesis at the gut-liver axis. Copyright © 2017 The Authors. Published by Elsevier B

Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein

PubMed Central

Park, Daeho; Han, Claudia; Elliott, Michael R.; Kinchen, Jason M.; Trampont, Paul C.; Das, Soumita; Collins, Sheila; Lysiak, Jeffrey J.; Hoehn, Kyle L.; Ravichandran, Kodi S.

2012-01-01

Rapid and efficient removal of apoptotic cells by phagocytes plays a key role during development, tissue homeostasis, and in controlling immune responses1–5. An important feature of efficient clearance is the capacity of a single phagocyte to ingest multiple apoptotic cells successively, and to process the increased load of corpse-derived cellular material6–9. However, factors that influence sustained phagocytic capacity or how they in turn influence continued clearance by phagocytes are not known. Here we identify that the ability of a phagocyte to control its mitochondrial membrane potential is a critical factor in the capacity of a phagocyte to engulf apoptotic cells. Changing the phagocyte mitochondrial membrane potential (genetically or pharmacologically) significantly affected phagocytosis, with lower potential enhancing engulfment and higher membrane potential inhibiting uptake. We then identified that Ucp2, a mitochondrial membrane protein that acts to lower the mitochondrial membrane potential10–12, is upregulated in phagocytes engulfing apoptotic cells (but not synthetic targets, bacteria, or yeast). Loss of Ucp2 limited the capacity of phagocytes to continually ingest apoptotic cells, while overexpression of Ucp2 increased the capacity for engulfment and the ability to engulf multiple apoptotic cells. Mutational and pharmacological inhibition of Ucp2 uncoupling activity reversed the positive effect of Ucp2 on engulfment capacity, suggesting a direct role for Ucp2-mediated mitochondrial function in phagocytosis. Macrophages from Ucp2-deficient mice13, 14 were impaired in their capacity to engulf apoptotic cells in vitro, and Ucp2-deficient mice displayed profound in vivo defects in clearing dying cells in the thymus and the testes. Collectively, these data suggest that phagocytes alter the mitochondrial membrane potential during engulfment to regulate uptake of sequential apoptotic cells, and that Ucp2 is a key molecular determinant of this step in

Dual clearance squeeze film damper

NASA Technical Reports Server (NTRS)

Fleming, D. P. (Inventor)

1985-01-01

A dual clearance hydrodynamic liquid squeeze film damper for a gas turbine engine is described. Under normal operating conditions, the device functions as a conventional squeeze film damper, using only one of its oil films. When an unbalance reaches abusive levels, as may occur with a blade loss or foreign object damage, a second, larger clearance film becomes active, controlling vibration amplitudes in a near optimum manner until the engine can be safely shut down and repaired.

Relative importance of magnetic moments in UXO clearance applications

USGS Publications Warehouse

Sanchez, V.; Li, Y.; Nabighian, M.; Wright, D.

2006-01-01

Surface magnetic anomaly observed in UXO clearance is mainly dipolar and, as a result, the dipole is the only moment used regularly in UXO applications. The dipole moment contains intensity of magnetization information but lacks shape information. Unlike dipole, higher-order moments, such as quadrupole and octupole, encode asymmetry properties of magnetization distribution within buried targets. In order to improve our understanding of magnetization distribution within UXO and non-UXO objects and its potential utility in UXO clearance, we present results of a 3D numerical modeling study for highly susceptible metallic objects. The basis for modeling is the solution of a nonlinear integral equation, describing magnetization within isolated objects, allowing us to compute magnetic moments of the object, analyze their relationships, and provide a depiction of the surface anomaly produced by the different moments within the object. Our modeling results show significant high-order moments for more asymmetric objects situated at typical UXO burial depths, and suggest that the increased relative contribution to magnetic gradient data from these higher-order moments may provide a practical tool for improved UXO discrimination. ?? 2005 Society of Exploration Geophysicists.

Latency reversal and viral clearance to cure HIV-1.

PubMed

Margolis, David M; Garcia, J Victor; Hazuda, Daria J; Haynes, Barton F

2016-07-22

Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication--a cure for AIDS. Paired testing of latency reversal and clearance strategies has begun, but additional obstacles to HIV eradication may emerge. Nevertheless, there is reason for optimism that advances in long-acting antiretroviral therapy and HIV prevention strategies will contribute to efforts in HIV cure research and that the implementation of these efforts will synergize to markedly blunt the effect of the HIV pandemic on society. Copyright © 2016, American Association for the Advancement of Science.

Appropriately Targeting Group Interventions for Academic Success Adopting the Clinical Model and PAR Profiles

ERIC Educational Resources Information Center

Johnson, Craig W.; Johnson, Ronald; Steigman, Michael; Odo, Chioma; Vijayan, Suvendra; Tata, Devadatta V.

2016-01-01

Prevalence of academic risk (PAR) group profiles provide data enabling empirically based group-specialized prescriptions for targeted academic success interventions to increase student retention, completion, and graduation rates, while improving allocation of institutional resources. Postsecondary student attrition engenders student debt,…

48 CFR 2452.237-75 - Clearance of contractor personnel.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Clearance of contractor... Clauses 2452.237-75 Clearance of contractor personnel. As prescribed in 2437.110(e), insert the following clause in solicitations and contracts. Clearance of Contractor Personnel (OCT 1999) (a) General. This...

30 CFR 56.9306 - Warning devices for restricted clearances.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

30 CFR 57.9306 - Warning devices for restricted clearances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Warning devices for restricted clearances. 57... Loading and Dumping Sites § 57.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

30 CFR 56.9306 - Warning devices for restricted clearances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

30 CFR 57.9306 - Warning devices for restricted clearances.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Warning devices for restricted clearances. 57... Loading and Dumping Sites § 57.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

30 CFR 57.9306 - Warning devices for restricted clearances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Warning devices for restricted clearances. 57... Loading and Dumping Sites § 57.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

30 CFR 57.9306 - Warning devices for restricted clearances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Warning devices for restricted clearances. 57... Loading and Dumping Sites § 57.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

30 CFR 56.9306 - Warning devices for restricted clearances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

30 CFR 56.9306 - Warning devices for restricted clearances.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

30 CFR 57.9306 - Warning devices for restricted clearances.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Warning devices for restricted clearances. 57... Loading and Dumping Sites § 57.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

30 CFR 56.9306 - Warning devices for restricted clearances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

14 CFR § 1260.63 - Customs clearance and visas.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Customs clearance and visas. § 1260.63... COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For grants or cooperative agreements with foreign organizations, this clause will be developed on...

Allometric scaling for predicting human clearance of bisphenol A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collet, Séverine H., E-mail: s.collet@envt.fr; Picard-Hagen, Nicole, E-mail: n.hagen-picard@envt.fr; Lacroix, Marlène Z., E-mail: m.lacroix@envt.fr

The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady statemore » volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min.« less

Systematic interrogation of diverse Omic data reveals interpretable, robust, and generalizable transcriptomic features of clinically successful therapeutic targets.

PubMed

Rouillard, Andrew D; Hurle, Mark R; Agarwal, Pankaj

2018-05-01

Target selection is the first and pivotal step in drug discovery. An incorrect choice may not manifest itself for many years after hundreds of millions of research dollars have been spent. We collected a set of 332 targets that succeeded or failed in phase III clinical trials, and explored whether Omic features describing the target genes could predict clinical success. We obtained features from the recently published comprehensive resource: Harmonizome. Nineteen features appeared to be significantly correlated with phase III clinical trial outcomes, but only 4 passed validation schemes that used bootstrapping or modified permutation tests to assess feature robustness and generalizability while accounting for target class selection bias. We also used classifiers to perform multivariate feature selection and found that classifiers with a single feature performed as well in cross-validation as classifiers with more features (AUROC = 0.57 and AUPR = 0.81). The two predominantly selected features were mean mRNA expression across tissues and standard deviation of expression across tissues, where successful targets tended to have lower mean expression and higher expression variance than failed targets. This finding supports the conventional wisdom that it is favorable for a target to be present in the tissue(s) affected by a disease and absent from other tissues. Overall, our results suggest that it is feasible to construct a model integrating interpretable target features to inform target selection. We anticipate deeper insights and better models in the future, as researchers can reuse the data we have provided to improve methods for handling sample biases and learn more informative features. Code, documentation, and data for this study have been deposited on GitHub at https://github.com/arouillard/omic-features-successful-targets.

19 CFR 4.61 - Requirements for clearance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... transported in-bond, or when they have unentered foreign merchandise aboard. For the purposes of the vessel clearance requirements, merchandise transported in-bond does not include bonded ship's stores or supplies. While American vessels transporting unentered foreign merchandise must fully comply with usual clearance...

48 CFR 952.204-73 - Facility clearance.

Code of Federal Regulations, 2014 CFR

2014-10-01

....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

48 CFR 952.204-73 - Facility clearance.

Code of Federal Regulations, 2011 CFR

2011-10-01

....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

48 CFR 952.204-73 - Facility clearance.

Code of Federal Regulations, 2012 CFR

2012-10-01

....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

48 CFR 952.204-73 - Facility clearance.

Code of Federal Regulations, 2013 CFR

2013-10-01

....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

48 CFR 952.204-73 - Facility clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

Impulsive response of an automatic transmission system with multiple clearances: Formulation, simulation and experiment

NASA Astrophysics Data System (ADS)

Crowther, Ashley R.; Singh, Rajendra; Zhang, Nong; Chapman, Chris

2007-10-01

Impulsive responses in geared systems with multiple clearances are studied when the mean torque excitation and system load change abruptly, with application to a vehicle driveline with an automatic transmission. First, torsional lumped-mass models of the planetary and differential gear sets are formulated using matrix elements. The model is then reduced to address tractable nonlinear problems while successfully retaining the main modes of interest. Second, numerical simulations for the nonlinear model are performed for transient conditions and a typical driving situation that induces an impulsive behaviour simulated. However, initial conditions and excitation and load profiles have to be carefully defined before the model can be numerically solved. It is shown that the impacts within the planetary or differential gears may occur under combinations of engine, braking and vehicle load transients. Our analysis shows that the shaping of the engine transient by the torque converter before reaching the clearance locations is more critical. Third, a free vibration experiment is developed for an analogous driveline with multiple clearances and three experiments that excite different response regimes have been carried out. Good correlations validate the proposed methodology.

Hepatic drug clearance following traumatic injury.

PubMed

Slaughter, R L; Hassett, J M

1985-11-01

Trauma is a complex disease state associated with physiologic changes that have the potential to alter hepatic drug clearance mechanisms. These responses include alterations in hepatic blood flow, reduction in hepatic microsomal activity, reduction in hepatic excretion processes, and changes in protein binding. Hepatic blood flow is influenced by sympathomimetic activity. Both animal and human studies demonstrate an initial reduction and subsequent increase in hepatic blood flow, which coincides with an observed increase and subsequent return to normal in serum catecholamine concentrations. Unfortunately, there are no human studies that address the importance these findings may have to the clearance processes of high intrinsic clearance compounds. Animal studies of trauma indicate that hepatic microsomal activity is depressed during the post-traumatic period. Reduction in the hepatic clearance of antipyrine, a model low intrinsic compound, has also been demonstrated in animal models of trauma. In addition to these effects, hepatic excretion of substances such as indocyanine green and bilirubin have been demonstrated to be impaired in both traumatized animals and humans. Finally, substantial increases in the serum concentration of the binding protein alpha 1-acid glycoprotein occur in trauma patients. This has been reported to be associated with subsequent decreases in the free fraction of lidocaine and quinidine. In addition to changing serum drug concentration/response relationships, the pharmacokinetic behavior of drugs bound to alpha 1-acid glycoprotein should also change. Preliminary observations in our laboratory in a dog model of surgically-induced trauma have shown a reduction in the total clearance of lidocaine and reduction in free lidocaine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury

PubMed Central

Vilay, A Mary; Churchwell, Mariann D; Mueller, Bruce A

2008-01-01

Decreased renal drug clearance is an obvious consequence of acute kidney injury (AKI). However, there is growing evidence to suggest that nonrenal drug clearance is also affected. Data derived from human and animal studies suggest that hepatic drug metabolism and transporter function are components of nonrenal clearance affected by AKI. Acute kidney injury may also impair the clearance of formed metabolites. The fact that AKI does not solely influence kidney function may have important implications for drug dosing, not only of renally eliminated drugs but also of those that are hepatically cleared. A review of the literature addressing the topic of drug metabolism and clearance alterations in AKI reveals that changes in nonrenal clearance are highly complicated and poorly studied, but they may be quite common. At present, our understanding of how AKI affects drug metabolism and nonrenal clearance is limited. However, based on the available evidence, clinicians should be cognizant that even hepatically eliminated drugs and formed drug metabolites may accumulate during AKI, and renal replacement therapy may affect nonrenal clearance as well as drug metabolite clearance. PMID:19040780

Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET.

PubMed

de Leon, Mony J; Li, Yi; Okamura, Nobuyuki; Tsui, Wai H; Saint-Louis, Les A; Glodzik, Lidia; Osorio, Ricardo S; Fortea, Juan; Butler, Tracy; Pirraglia, Elizabeth; Fossati, Silvia; Kim, Hee-Jin; Carare, Roxana O; Nedergaard, Maiken; Benveniste, Helene; Rusinek, Henry

2017-09-01

Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Dynamic PET with 18 F-THK5117, a tracer for tau pathology, was used to estimate the ventricular CSF time-activity as a biomarker for CSF clearance. We tested 3 hypotheses: extracranial CSF is detected at the superior turbinates; CSF clearance is reduced in AD; and CSF clearance is inversely associated with amyloid deposition. Methods: Fifteen subjects, 8 with AD and 7 normal control volunteers, were examined with 18 F-THK5117. Ten subjects additionally underwent 11 C-Pittsburgh compound B ( 11 C-PiB) PET scanning, and 8 were 11 C-PiB-positive. Ventricular time-activity curves of 18 F-THK5117 were used to identify highly correlated time-activity curves from extracranial voxels. Results: For all subjects, the greatest density of CSF-positive extracranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinate CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET-measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Numerical investigation of hub clearance flow in a Kaplan turbine

NASA Astrophysics Data System (ADS)

Wu, H.; Feng, J. J.; Wu, G. K.; Luo, X. Q.

2012-11-01

In this paper, the flow field considering the hub clearance flow in a Kaplan turbine has been investigated through using the commercial CFD code ANSYS CFX based on high-quality structured grids generated by ANSYS ICEM CFD. The turbulence is simulated by k-ω based shear stress transport (SST) turbulence model together with automatic near wall treatments. Four kinds of simulations have been conducted for the runner geometry without hub clearance, with only the hub front clearance, with only the rear hub clearance, and with both front and rear clearance. The analysis of the obtained results is focused on the flow structure of the hub clearance flow, the effect on the turbine performance including hydraulic efficiency and cavitation performance, which can improve the understanding on the flow field in a Kaplan turbine.

Inherited Disorders of Bilirubin Clearance

PubMed Central

Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

2016-01-01

Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

A novel approach to achieving modular retrovirus clearance for a parvovirus filter.

PubMed

Stuckey, Juliana; Strauss, Daniel; Venkiteshwaran, Adith; Gao, Jinxin; Luo, Wen; Quertinmont, Michelle; O'Donnell, Sean; Chen, Dayue

2014-01-01

Viral filtration is routinely incorporated into the downstream purification processes for the production of biologics produced in mammalian cell cultures (MCC) to remove potential viral contaminants. In recent years, the use of retentive filters designed for retaining parvovirus (~20 nm) has become an industry standard in a conscious effort to further improve product safety. Since retentive filters remove viruses primarily by the size exclusion mechanism, it is expected that filters designed for parvovirus removal can effectively clear larger viruses such as retroviruses (~100 nm). In an attempt to reduce the number of viral clearance studies, we have taken a novel approach to demonstrate the feasibility of claiming modular retrovirus clearance for Asahi Planova 20N filters. Porcine parvovirus (PPV) and xenotropic murine leukemia virus (XMuLV) were co-spiked into six different feedstreams and then subjected to laboratory scale Planova 20N filtration. Our results indicate that Planova 20N filters consistently retain retroviruses and no retrovirus has ever been detected in the filtrates even when significant PPV breakthrough is observed. Based on the data from multiple in-house viral validation studies and the results from the co-spiking experiments, we have successfully claimed a modular retrovirus clearance of greater than 6 log10 reduction factors (LRF) to support clinical trial applications in both USA and Europe. © 2013 American Institute of Chemical Engineers.

Assessment of kidney function in children by enzymatic determination of 2- or 24-h creatinine clearance: comparison with inulin clearance.

PubMed

Uemura, Osamu; Nagai, Takuhito; Yamakawa, Satoshi; Kaneko, Tetsuji; Hibi, Yoshiko; Yamasaki, Yasuhito; Yamamoto, Masaki; Nakano, Masaru; Iwata, Naoyuki; Hibino, Satoshi

2016-06-01

Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children. Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time. Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr. Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients.

Peritoneal clearances in hypertensive CAPD patients after oral administration of clonidine, enalapril, and nifedipine.

PubMed

Favazza, A; Motanaro, D; Messa, P; Antonucci, F; Gropuzzo, M; Mioni, G

1992-01-01

The authors investigated whether the reduction of arterial pressure, induced by the oral administration of clonidine (CLO), enalapril (EN), and nifedipine (NIF), has any effect on peritoneal transport rates. The study was performed in nine hypertensive patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The patients were submitted to administration of CLO, EN, and NIF, each in randomized succession for two weeks, after withdrawal of any hypotensive therapy for eight days (washout period). The nine patients underwent a four-hour dwell exchange using a 2.27 g/dL glucose two-liter bag after washout and after each hypotensive period. The following parameters were analyzed: mean arterial pressure (MAP), performed in the sitting position; net ultrafiltration; effluent/initial dialysate glucose ratio (GL D/Do); peritoneal clearance of K, BUN, creatinine (Cr), phosphate, beta-2 microglobulin (beta 2), total proteins, and the ratio between beta 2 and Cr clearance. Moreover, residual renal Cr and beta 2 clearances were analyzed. The three drugs significantly reduced MAP at a similar rate. The peritoneal transport parameters after CLO were similar to the results in the washout period. On the contrary, after EN and NIF therapy, Cr and beta 2 clearances were significantly increased, and GL D/Do decreased in comparison to the washout period. The other peritoneal transport parameters after EN and NIF were similar to the washout period. Residual renal Cr and beta 2 clearances after the three drugs were similar to those in the washout. these data suggest that after two weeks of therapy with EN and NIF, glucose, Cr, and beta 2 peritoneal transports are influenced by these hypotensive drugs irrespective of the effect on the arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Modified Augmented Renal Clearance Score Predicts Rapid Piperacillin and Tazobactam Clearance in Critically Ill Surgery and Trauma Patients

DTIC Science & Technology

2014-04-24

intermittent dosing regimens. CONCLUSION: Given its ability to predict antimicrobial clearance above populationmedians, which could compromise therapy, the...campaign dedicated to improve out- comes.1,2 In the era ofmultiply drug- resistant pathogens and rising antimicrobial minimum inhibitory concentrations (MICs...urinary creatinine clearance significantly exceeds what is predicted by the serum creatinine concentration according to various mathematical

Voltammetric and Mathematical Evidence for Dual Transport Mediation of Serotonin Clearance In Vivo

PubMed Central

Wood, Kevin M.; Zeqja, Anisa; Nijhout, H. Frederik; Reed, Michael C.; Best, Janet; Hashemi, Parastoo

2014-01-01

The neurotransmitter serotonin underlies many of the brain’s functions. Understanding serotonin neurochemistry is important for improving treatments for neuropsychiatric disorders such as depression. Antidepressants commonly target serotonin clearance via serotonin transporters (SERTs) and have variable clinical effects. Adjunctive therapies, targeting other systems including serotonin autoreceptors, also vary clinically and carry adverse consequences. Fast scan cyclic voltammetry (FSCV) is particularly well suited for studying antidepressant effects on serotonin clearance and autoreceptors by providing real-time chemical information on serotonin kinetics in vivo. However, the complex nature of in vivo serotonin responses makes it difficult to interpret experimental data with established kinetic models. Here, we electrically stimulated the mouse medial forebrain bundle (MFB) to provoke and detect terminal serotonin in the substantia nigra reticulata (SNr). In response to MFB stimulation we found three dynamically distinct serotonin signals. To interpret these signals we developed a computational model that supports two independent serotonin reuptake mechanisms (high affinity, low efficiency reuptake mechanism and low affinity, high efficiency reuptake system) and bolsters an important inhibitory role for the serotonin autoreceptors. Our data and analysis, afforded by the powerful combination of voltammetric and theoretical methods, gives new understanding of the chemical heterogeneity of serotonin dynamics in the brain. This diverse serotonergic matrix likely contributes to clinical variability of antidepressants. PMID:24702305

Postoperative ERCP versus laparoscopic choledochotomy for clearance of selected bile duct calculi: a randomized trial.

PubMed

Nathanson, Leslie K; O'Rourke, Nicholas A; Martin, Ian J; Fielding, George A; Cowen, Alistair E; Roberts, Roderick K; Kendall, Bradley J; Kerlin, Paul; Devereux, Benedict M

2005-08-01

Prospectively evaluate whether for patients having laparoscopic cholecystectomy with failed trans-cystic duct clearance of bile duct (BD) stones they should have laparoscopic choledochotomy or postoperative endoscopic retrograde cholangiography (ERCP). Clinical management of BD stones found at laparoscopic cholecystectomy in the last decade has focused on pre-cholecystectomy detection with ERCP clearance in those with suspected stones. This clinical algorithm successfully clears the stones in most patients, but no stones are found in 20% to 60% of patients and rare unpredictably severe ERCP morbidity can result in this group. Our initial experience of 300 consecutive patients with fluoroscopic cholangiography and intraoperative clearance demonstrated that, for the pattern of stone disease we see, 66% of patients' BD stones can be cleared via the cystic duct with dramatic reduction in morbidity compared to the 33% requiring choledochotomy or ERCP. Given the limitations of the preoperative approach to BD stone clearance, this trial was designed to explore the limitations, for patients failing laparoscopic trans-cystic clearance, of laparoscopic choledochotomy or postoperative ERCP. Across 7 metropolitan hospitals after failed trans-cystic duct clearance, patients were intraoperatively randomized to have either laparoscopic choledochotomy or postoperative ERCP. Exclusion criteria were: ERCP prior to referral for cholecystectomy, severe cholangitis or pancreatitis requiring immediate ERCP drainage, common BD diameter of less than 7 mm diameter, or if bilio-enteric drainage was required in addition to stone clearance. Drain decompression of the cleared BD was used in the presence of cholangitis, an edematous ampulla due to instrumentation or stone impaction and technical difficulties from local inflammation and fibrosis. The ERCP occurred prior to discharge from hospital. Mechanical and extracorporeal shockwave lithotripsy was available. Sphincter balloon dilation as an

Advanced optical blade tip clearance measurement system

NASA Technical Reports Server (NTRS)

Ford, M. J.; Honeycutt, R. E.; Nordlund, R. E.; Robinson, W. W.

1978-01-01

An advanced electro-optical system was developed to measure single blade tip clearances and average blade tip clearances between a rotor and its gas path seal in an operating gas turbine engine. This system is applicable to fan, compressor, and turbine blade tip clearance measurement requirements, and the system probe is particularly suitable for operation in the extreme turbine environment. A study of optical properties of blade tips was conducted to establish measurement system application limitations. A series of laboratory tests was conducted to determine the measurement system's operational performance characteristics and to demonstrate system capability under simulated operating gas turbine environmental conditions. Operational and environmental performance test data are presented.

19 CFR 4.61 - Requirements for clearance.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE... made by filing Customs Form 1300 (Vessel Entrance or Clearance Statement) executed by the vessel master...

19 CFR 4.61 - Requirements for clearance.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE... made by filing Customs Form 1300 (Vessel Entrance or Clearance Statement) executed by the vessel master...

19 CFR 4.61 - Requirements for clearance.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE... made by filing Customs Form 1300 (Vessel Entrance or Clearance Statement) executed by the vessel master...

19 CFR 4.61 - Requirements for clearance.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE... made by filing Customs Form 1300 (Vessel Entrance or Clearance Statement) executed by the vessel master...

Axial compressor blade design for desensitization of aerodynamic performance and stability to tip clearance

NASA Astrophysics Data System (ADS)

Erler, Engin

of the local blade passage. These flow features are isolated and validated based on the reference rotor design through changes in the inlet total pressure condition to alter incoming flow momentum and blade number count to change double leakage rate. In terms of flow mechanism, double leakage is shown to be detrimental to performance and stability, and its proportional increase with tip clearance size explains the sensitivity increase in the presence of double leakage and, conversely, the desensitization effect of reducing or eliminating double leakage. The increase in incoming meridional momentum in the tip region reduces sensitivity to tip clearance through its reduction of double leakage as well as through improved mixing with tip clearance flow, as demonstrated by an analytical model without double leakage flow. The above results imply that any blade design strategy that exploits the two desensitizing flow features would reduce the performance and stability sensitivity to tip clearance size. The increase of the incoming meridional momentum can be achieved through forward chordwise sweep of the blade. The reduction of double leakage without changing blade pitch can be obtained by decreasing the blade stagger angle in the tip region. Examples of blade designs associated with these strategies are shown through CFX simulations to be successful in reducing sensitivity to tip clearance size.

Test Rig for Evaluating Active Turbine Blade Tip Clearance Control Concepts

NASA Technical Reports Server (NTRS)

Lattime, Scott B.; Steinetz, Bruce M.; Robbie, Malcolm G.

2003-01-01

Improved blade tip sealing in the high pressure compressor and high pressure turbine can provide dramatic improvements in specific fuel consumption, time-on-wing, compressor stall margin and engine efficiency as well as increased payload and mission range capabilities of both military and commercial gas turbine engines. The preliminary design of a mechanically actuated active clearance control (ACC) system for turbine blade tip clearance management is presented along with the design of a bench top test rig in which the system is to be evaluated. The ACC system utilizes mechanically actuated seal carrier segments and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. The purpose of this active clearance control system is to improve upon current case cooling methods. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, re-burst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). The active turbine blade tip clearance control system design presented herein will be evaluated to ensure that proper response and positional accuracy is achievable under simulated high-pressure turbine conditions. The test rig will simulate proper seal carrier pressure and temperature loading as well as the magnitudes and rates of blade tip clearance changes of an actual gas turbine engine. The results of these evaluations will be presented in future works.

Adequacy of peritoneal dialysis: beyond small solute clearance.

PubMed

Goldberg, Ryan; Yalavarthy, Rajesh; Teitelbaum, Isaac

2009-01-01

Peritoneal dialysis adequacy is monitored primarily by indices of small solute clearance, Kt/V(urea) and creatinine clearance (C(cr)). Once a threshold of adequacy has been obtained, however, increasing small solute clearance does not result in improved long-term outcomes of PD patients. There are several other factors that may affect optimal dialysis outcomes. These include, but are not limited to: ultrafiltration, inflammation, malnutrition, and mineral metabolism. In this article, we will briefly review data regarding the relationships between these factors and survival on PD.

The tear turnover and tear clearance tests - a review.

PubMed

Garaszczuk, Izabela K; Montes Mico, Robert; Iskander, D Robert; Expósito, Alejandro Cerviño

2018-03-01

The aim is to provide a summary of methods available for the assessment of tear turnover and tear clearance rates. The review defines tear clearance and tear turnover and describes their implication for ocular surface health. Additionally, it describes main types of techniques for measuring tear turnover, including fluorescein tear clearance tests, techniques utilizing electromagnetic spectrum and tracer molecule and novel experimental techniques utilizing optical coherence tomography and fluorescein profilometry. Areas covered: Internet databases (PubMed, Science Direct, Google Scholar) and most frequently cited references were used as a principal resource of information on tear turnover rate and tear clearance rate, presenting methodologies and equipment, as well as their definition and implications for the anterior eye surface health and function. Keywords used for data-search were as follows: tear turnover, tear clearance, fluorescein clearance, scintigraphy, fluorophotometry, tear flow, drainage, tear meniscus dynamics, Krehbiel flow and lacrimal functional unit. Expert commentary: After decades, the topic of tear turnover assessment has been reintroduced. Recently, new techniques have been developed to propose less invasive, less time consuming and simpler methodologies for the assessment of tear dynamics that have the potential to be utilized in clinical practice.

Lactate clearance as a marker of mortality in pediatric intensive care unit.

PubMed

Munde, A; Kumar, N; Beri, R S; Puliyel, J M

2014-07-01

To correlate lactate clearance with Pediatric Intensive Care Unit (PICU) mortality. 45 (mean age 40.15 mo, 60% males) consecutive admissions in the PICU were enrolled between May 2012 to June 2013. Lactate clearance (Lactate level at admission - level 6 hr later x 100 / lactate level at admission) in first 6 hours of hospitalization was correlated to in-hospital mortality and PRISM score. Twelve out of 45 patients died. 90% died among those with delayed/poor clearance (clearance <30%) compared to 8.5% in those with good clearance (clearance >30%) (P<0.001). Lactate clearance <30% predicted mortality with sensitivity of 75%, specificity of 97%, positive predictive value of 90%, and negative predictive value of 91.42%. Predictability was comparable to PRISM score >30. Lactate clearance at six hours correlates with mortality in the PICU.

46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

Code of Federal Regulations, 2014 CFR

2014-10-01

... worn down to 6.4 mm (0.25 in) clearance for shafts of 229 mm (9 in) or less in diameter, 7.95 mm (0.3125 in) clearance for shafts exceeding 229 mm (9 in) but not exceeding 305 mm (12 in) in diameter, and 9.53 mm (0.375 in) clearance for shafts exceeding 305 mm (12 in) in diameter. (2) Where the...

46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

Code of Federal Regulations, 2012 CFR

2012-10-01

... worn down to 6.4 mm (0.25 in) clearance for shafts of 229 mm (9 in) or less in diameter, 7.95 mm (0.3125 in) clearance for shafts exceeding 229 mm (9 in) but not exceeding 305 mm (12 in) in diameter, and 9.53 mm (0.375 in) clearance for shafts exceeding 305 mm (12 in) in diameter. (2) Where the...

46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

Code of Federal Regulations, 2010 CFR

2010-10-01

... worn down to 6.4 mm (0.25 in) clearance for shafts of 229 mm (9 in) or less in diameter, 7.95 mm (0.3125 in) clearance for shafts exceeding 229 mm (9 in) but not exceeding 305 mm (12 in) in diameter, and 9.53 mm (0.375 in) clearance for shafts exceeding 305 mm (12 in) in diameter. (2) Where the...

46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

Code of Federal Regulations, 2011 CFR

2011-10-01

... worn down to 6.4 mm (0.25 in) clearance for shafts of 229 mm (9 in) or less in diameter, 7.95 mm (0.3125 in) clearance for shafts exceeding 229 mm (9 in) but not exceeding 305 mm (12 in) in diameter, and 9.53 mm (0.375 in) clearance for shafts exceeding 305 mm (12 in) in diameter. (2) Where the...

46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

Code of Federal Regulations, 2013 CFR

2013-10-01

... worn down to 6.4 mm (0.25 in) clearance for shafts of 229 mm (9 in) or less in diameter, 7.95 mm (0.3125 in) clearance for shafts exceeding 229 mm (9 in) but not exceeding 305 mm (12 in) in diameter, and 9.53 mm (0.375 in) clearance for shafts exceeding 305 mm (12 in) in diameter. (2) Where the...

Effect of clearance on cartilage tribology in hip hemi-arthroplasty.

PubMed

Lizhang, Jia; Taylor, Simon D; Jin, Zhongmin; Fisher, John; Williams, Sophie

2013-12-01

Hemi-arthroplasty of the hip (an artificial femoral head articulating against the natural acetabulum) is used to treat fractured necks of femur; however, there is evidence that articulation causes erosion of the cartilage, resulting in pain for the patient. Parameters that may influence this cartilage erosion include head material and roughness, clearance between the head and acetabulum and activity levels of the patient. This study has assessed the effect of clearance of hemi-arthroplasty articulations on the contact stress, friction and cartilage deformation in an in vitro tribological simulation of the hemi-arthroplasty joint that applied dynamic loads and motion. It has been demonstrated that peak contact stress increased from 5.6 to 10.6 MPa as radial clearance increased from small (<0.6 mm) to extra-large (>1.8 mm). In all samples, friction factor increased with time and was significantly less with extra-large clearances compared to small (<0.6 mm), medium (0.6-1.2 mm) and large (1.2-1.8 mm) clearances. The cartilage deformation observed was significantly greater in acetabulum samples paired to give small or extra-large clearances compared to those with medium or large clearances.

Effects of block copolymer properties on nanocarrier protection from in vivo clearance

PubMed Central

D’Addio, Suzanne M.; Saad, Walid; Ansell, Steven M.; Squiers, John J.; Adamson, Douglas; Herrera-Alonso, Margarita; Wohl, Adam R.; Hoye, Thomas R.; Macosko, Christopher W.; Mayer, Lawrence D.; Vauthier, Christine; Prud’homme, Robert K.

2012-01-01

Drug nanocarrier clearance by the immune system must be minimized to achieve targeted delivery to pathological tissues. There is considerable interest in finding in vitro tests that can predict in vivo clearance outcomes. In this work, we produce nanocarriers with dense PEG layers resulting from block copolymer-directed assembly during rapid precipitation. Nanocarriers are formed using block copolymers with hydrophobic blocks of polystyrene (PS), poly-ε-caprolactone (PCL), poly-D,L-lactide (PLA), or poly-lactide-co-glycolide (PLGA), and hydrophilic blocks of polyethylene glycol (PEG) with molecular weights from 1.5 kg/mol to 9 kg/mol. Nanocarriers with paclitaxel prodrugs are evaluated in vivo in Foxn1nu mice to determine relative rates of clearance. The amount of nanocarrier in circulation after 4 h varies from 10% to 85% of initial dose, depending on the block copolymer. In vitro complement activation assays are conducted in an effort to correlate the protection of the nanocarrier surface from complement binding and activation and in vivo circulation. Guidelines for optimizing block copolymer structure to maximize circulation of nanocarriers formed by rapid precipitation and directed assembly are proposed, relating to the relative size of the hydrophilic and hydrophobic block, the hydrophobicity of the anchoring block, the absolute size of the PEG block, and polymer crystallinity. The in vitro results distinguish between the poorly circulating PEG5k-PCL9k and the better circulating nanocarriers, but could not rank the better circulating nanocarriers in order of circulation time. Analysis of PEG surface packing on monodisperse 200 nm latex spheres indicates that the sizes of the hydrophobic PCL, PS, and PLA blocks are correlated with the PEG blob size, and possibly the clearance from circulation. Suggestions for next step in vitro measurements are made. PMID:22732478

Further Characterization of an Active Clearance Control Concept

NASA Technical Reports Server (NTRS)

Taylor, Shawn C.; Steinetz, Bruce M.; Oswald, Jay J.

2007-01-01

A new test chamber and precision hydraulic actuation system were incorporated into an active clearance control (ACC) test rig at NASA Glenn Research Center. Using the improved system, a fast-acting, mechanically-actuated, ACC concept was evaluated at engine simulated temperatures and pressure differentials up to 1140 F and 120 psig, on the basis of secondary seal leakage and kinematic controllability. During testing, the ACC concept tracked a simulated flight clearance transient profile at 1140 F, 120 psig, with a maximum error of only 0.0012 in. Comparison of average dynamic leakage of the system with average static leakage did not show significant differences between the two operating conditions. Calculated effective clearance values for the rig were approximately 0.0002 in. at 120 psig, well below the industry specified effective clearance threshold of 0.001 in.

LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons.

PubMed

Kwon, Seok-Kyu; Sando, Richard; Lewis, Tommy L; Hirabayashi, Yusuke; Maximov, Anton; Polleux, Franck

2016-07-01

Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demonstrate that the presence or absence of mitochondria at presynaptic boutons dictates neurotransmitter release properties through Mitochondrial Calcium Uniporter (MCU)-dependent Ca2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca2+ uptake at glutamatergic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mechanisms whereby mitochondria control neurotransmitter release properties in a bouton-specific way through presynaptic Ca2+ clearance.

The role of lectins and glycans in platelet clearance

PubMed Central

Hoffmeister, Karin M.

2015-01-01

Summary In recent years, it has become increasingly apparent that the life span of transfused platelets in circulation is regulated, at least in part, by glycan-lectin mediated mechanisms. There is clear evidence that refrigerated platelets are cleared by glycan-lectin mediated clearance mechanisms. Acute platelet cooling clusters glycoprotein (GP) Ibα receptors bearing uncovered N-acetylglucosamine (GlcNAc), and αMβ2 integrins on hepatic macrophages recognise clustered GlcNAc to rapidly clear these platelets from circulation. With prolonged refrigeration GPIbα clustering bearing uncovered galactose increases, which mediates the removal of long-term refrigerated platelets via hepatic Ashwell-Morell receptors (AMR), originally named as asialoglycoprotein receptors. In contrast, little is known about the molecular mechanisms of transfused room temperature platelet clearance. This review examines the role of glycan-lectin mediated clearance of exogenous, i.e. transfused chilled platelet clearance and briefly addresses the current knowledge of stored platelet function, degradation and its relation to platelet clearance. PMID:21781240

Automation for "Direct-to" Clearances in Air-Traffic Control

NASA Technical Reports Server (NTRS)

Erzberger, Heinz; McNally, David

2006-01-01

A method of automation, and a system of computer hardware and software to implement the method, have been invented to assist en-route air-traffic controllers in the issuance of clearances to fly directly to specified waypoints or navigation fixes along straight paths that deviate from previously filed flight plans. Such clearances, called "direct-to" clearances, have been in use since before the invention of this method and system.

Quantitative Magnetic Particle Imaging Monitors the Transplantation, Biodistribution, and Clearance of Stem Cells In Vivo

PubMed Central

Zheng, Bo; von See, Marc P.; Yu, Elaine; Gunel, Beliz; Lu, Kuan; Vazin, Tandis; Schaffer, David V.; Goodwill, Patrick W.; Conolly, Steven M.

2016-01-01

Stem cell therapies have enormous potential for treating many debilitating diseases, including heart failure, stroke and traumatic brain injury. For maximal efficacy, these therapies require targeted cell delivery to specific tissues followed by successful cell engraftment. However, targeted delivery remains an open challenge. As one example, it is common for intravenous deliveries of mesenchymal stem cells (MSCs) to become entrapped in lung microvasculature instead of the target tissue. Hence, a robust, quantitative imaging method would be essential for developing efficacious cell therapies. Here we show that Magnetic Particle Imaging (MPI), a novel technique that directly images iron-oxide nanoparticle-tagged cells, can longitudinally monitor and quantify MSC administration in vivo. MPI offers near-ideal image contrast, depth penetration, and robustness; these properties make MPI both ultra-sensitive and linearly quantitative. Here, we imaged, for the first time, the dynamic trafficking of intravenous MSC administrations using MPI. Our results indicate that labeled MSC injections are immediately entrapped in lung tissue and then clear to the liver within one day, whereas standard iron oxide particle (Resovist) injections are immediately taken up by liver and spleen. Longitudinal MPI-CT imaging also indicated a clearance half-life of MSC iron oxide labels in the liver at 4.6 days. Finally, our ex vivo MPI biodistribution measurements of iron in liver, spleen, heart, and lungs after injection showed excellent agreement (R2 = 0.943) with measurements from induction coupled plasma spectrometry. These results demonstrate that MPI offers strong utility for noninvasively imaging and quantifying the systemic distribution of cell therapies and other therapeutic agents. PMID:26909106

Long-term clearance from small airways in patients with cystic fibrosis.

PubMed

Lindström, M; Camner, P; Falk, R; Hjelte, L; Philipson, K; Svartengren, M

2005-02-01

Impaired mucociliary clearance is a hallmark of cystic fibrosis (CF). Early morphological changes first appear in the small airways. Lung clearance was investigated in 11 young CF adults with mild-to-moderate lung disease using a method depositing particles mainly in the small airways. Radiolabelled Teflon particles (6 microm) were inhaled with an extremely slow inhalation flow, 0.05 L x s(-1). Lung retention was measured immediately following inhalations and, on four occasions up to 21 days. The results were compared with data from healthy subjects. The lung retention at 24 h in % of deposition was 67% (95% confidence interval 58-76) in the CF patients, compared to 48% (42-53) in the healthy subjects. Clearance on days 1-7 was larger in the CF patients, 22% (15-29) compared to the healthy subjects, 14% (12-16). No difference was observed between the CF patients and the healthy subjects in the slow clearance phase at day 7 to day 21, representing small airway clearance. Impaired mucociliary clearance in CF patients results in increased 24-h retention and a prolonged rapid clearance phase. The results of the study do not support the current authors' hypothesis that clearance from small airways is slower in cystic fibrosis patients compared to healthy subjects. Furthermore, the data suggest that mucociliary transport is not the dominant clearance mechanism in small airways.

An OX40/OX40L interaction directs successful immunity to hepatitis B virus

PubMed Central

Publicover, Jean; Gaggar, Anuj; Jespersen, Jillian M.; Halac, Ugur; Johnson, Audra J.; Goodsell, Amanda; Avanesyan, Lia; Nishimura, Stephen L.; Holdorf, Meghan; Mansfield, Keith G.; Judge, Joyce Bousquet; Koshti, Arya; Croft, Michael; Wakil, Adil E.; Rosenthal, Philip; Pai, Eric; Cooper, Stewart; Baron, Jody L.

2018-01-01

Depending on age of acquisition, hepatitis B virus (HBV) can induce a cell-mediated immune response that results in either cure or progressive liver injury. In adult-acquired infection, HBV antigens are usually cleared, whereas in infancy-acquired infection, they persist. Individuals infected during infancy therefore represent the majority of patients chronically infected with HBV (CHB). A therapy that can promote viral antigen clearance in most CHB patients has not been developed and would represent a major health care advance and cost mitigator. Using an age-dependent mouse model of HBV clearance and persistence in conjunction with human blood and liver tissue, we studied mechanisms of viral clearance to identify new therapeutic targets. We demonstrate that age-dependent expression of the costimulatory molecule OX40 ligand (OX40L) by hepatic innate immune cells is pivotal in determining HBV immunity, and that treatment with OX40 agonists leads to improved HBV antigen clearance in young mice, as well as increased strength of T cell responses in young mice and adult mice that were exposed to HBV when they were young and developed a CHB serological profile. Similarly, in humans, we show that hepatic OX40L transcript expression is age-dependent and that increased OX40 expression on peripheral CD4+ T cells in adults is associated with HBV clearance. These findings provide new mechanistic understanding of the immune pathways and cells necessary for HBV immunity and identify potential therapeutic targets for resolving CHB. PMID:29563320

Small molecule LX2343 ameliorates cognitive deficits in AD model mice by targeting both amyloid β production and clearance.

PubMed

Guo, Xiao-Dan; Sun, Guang-Long; Zhou, Ting-Ting; Xu, Xin; Zhu, Zhi-Yuan; Rukachaisirikul, Vatcharin; Hu, Li-Hong; Shen, Xu

2016-09-01

Streptozotocin (STZ) is widely used to induce oxidative damage and to impair glucose metabolism, apoptosis, and tau/Aβ pathology, eventually leading to cognitive deficits in both in vitro and in vivo models of Alzheimer's disease (AD). In this study, we constructed a cell-based platform using STZ to induce stress conditions mimicking the complicated pathologies of AD in vitro, and evaluated the anti-amyloid effects of a small molecule, N-(1,3-benzodioxol-5-yl)-2-[5-chloro-2-methoxy(phenylsulfonyl)anilino]acetamide (LX2343) in the amelioration of cognitive deficits in AD model mice. Cell-based assays for screening anti-amyloid compounds were established by assessing Aβ accumulation in HEK293-APP sw and CHO-APP cells, and Aβ clearance in primary astrocytes and SH-SY5Y cells after the cells were treated with STZ in the presence of the test compounds. Autophagic flux was observed using confocal laser scanning microscopy. APP/PS1 transgenic mice were administered LX2343 (10 mg·kg -1 ·d -1 , ip) for 100 d. After LX2343 administration, cognitive ability of the mice was evaluated using Morris water maze test, and senile plaques in the brains were detected using Thioflavine S staining. ELISA assay was used to evaluate Aβ and sAPPβ levels, while Western blot analysis was used to measure the signaling proteins in both cell and animal brains. LX2343 (5-20 μmol/L) dose-dependently decreased Aβ accumulation in HEK293-APP sw and CHO-APP cells, and promoted Aβ clearance in SH-SY5Y cells and primary astrocytes. The anti-amyloid effects of LX2343 were attributed to suppressing JNK-mediated APP Thr668 phosphorylation, thus inhibiting APP cleavage on one hand, and inhibiting BACE1 enzymatic activity with an IC 50 value of 11.43±0.36 μmol/L, on the other hand. Furthermore, LX2343 acted as a non-ATP competitive PI3K inhibitor to negatively regulate AKT/mTOR signaling, thus promoting autophagy, and increasing Aβ clearance. Administration of LX2343 in APP/PS1 transgenic mice

Clearance detector and method for motion and distance

DOEpatents

Xavier, Patrick G [Albuquerque, NM

2011-08-09

A method for correct and efficient detection of clearances between three-dimensional bodies in computer-based simulations, where one or both of the volumes is subject to translation and/or rotations. The method conservatively determines of the size of such clearances and whether there is a collision between the bodies. Given two bodies, each of which is undergoing separate motions, the method utilizes bounding-volume hierarchy representations for the two bodies and, mappings and inverse mappings for the motions of the two bodies. The method uses the representations, mappings and direction vectors to determine the directionally furthest locations of points on the convex hulls of the volumes virtually swept by the bodies and hence the clearance between the bodies, without having to calculate the convex hulls of the bodies. The method includes clearance detection for bodies comprising convex geometrical primitives and more specific techniques for bodies comprising convex polyhedra.

Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis.

PubMed

Ma, Ruishuang; Xie, Rui; Yu, Chengyuan; Si, Yu; Wu, Xiaoming; Zhao, Lu; Yao, Zhipeng; Fang, Shaohong; Chen, He; Novakovic, Valerie; Gao, Chunyan; Kou, Junjie; Bi, Yayan; Thatte, Hemant S; Yu, Bo; Yang, Shufen; Zhou, Jin; Shi, Jialan

2017-07-10

The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes. Activated platelets adhered were and ultimately digested by ECs in vivo and in vitro. Blocking PS on platelets or αvβ3 integrin on ECs attenuated platelet clearance resulting in increased platelet count in a mouse model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding decrease in platelet-leukocyte complex formation and markedly reduced generation of factor Xa and thrombin on platelets. Pretreatment with lactadherin significantly increased phagocytosis of platelets by approximately 2-fold, diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin formation by 50%. Our results suggest that PS-mediated clearance of activated platelets by the endothelium results in an anti-inflammatory, anticoagulant, and antithrombotic effect that contribute to maintaining platelet homeostasis during acute inflammation. These results suggest a new therapeutic target for impeding the development of DIC.

Acupuncture promotes mTOR-independent autophagic clearance of aggregation-prone proteins in mouse brain.

PubMed

Tian, Tian; Sun, Yanhong; Wu, Huangan; Pei, Jian; Zhang, Jing; Zhang, Yi; Wang, Lu; Li, Bin; Wang, Lihua; Shi, Jiye; Hu, Jun; Fan, Chunhai

2016-01-21

Acupuncture has historically been practiced to treat medical disorders by mechanically stimulating specific acupoints with fine needles. Despite its well-documented efficacy, its biological basis remains largely elusive. In this study, we found that mechanical stimulation at the acupoint of Yanglingquan (GB34) promoted the autophagic clearance of α-synuclein (α-syn), a well known aggregation-prone protein closely related to Parkinson's disease (PD), in the substantia nigra par compacta (SNpc) of the brain in a PD mouse model. We found the protein clearance arose from the activation of the autophagy-lysosome pathway (ALP) in a mammalian target of rapamycin (mTOR)-independent approach. Further, we observed the recovery in the activity of dopaminergic neurons in SNpc, and improvement in the motor function at the behavior level of PD mice. Whereas acupuncture and rapamycin, a chemical mTOR inhibitor, show comparable α-syn clearance and therapeutic effects in the PD mouse model, the latter adopts a distinctly different, mTOR-dependent, autophagy induction process. Due to this fundamental difference, acupuncture may circumvent adverse effects of the rapamycin treatment. The newly discovered connection between acupuncture and autophagy not only provides a new route to understanding the molecular mechanism of acupuncture but also sheds new light on cost-effective and safe therapy of neurodegenerative diseases.

2015 Annual Report on Security Clearance Determinations

DTIC Science & Technology

2016-06-28

completed or pending security clearance determinations for government employees and contractors during the preceding fiscal year that have taken longer...each level during the preceding fiscal year. Similar data pertaining to USG contractors is also required. Also, for each element of the Intelligence...for USG Employees and USG Contractors Security Clearance Determination Processing Metrics for the Seven IC Agencies The number of individuals

Dynamic modelling and experimental study of cantilever beam with clearance

NASA Astrophysics Data System (ADS)

Li, B.; Jin, W.; Han, L.; He, Z.

2012-05-01

Clearances occur in almost all mechanical systems, typically such as the clearance between slide plate of gun barrel and guide. Therefore, to study the clearances of mechanisms can be very important to increase the working performance and lifetime of mechanisms. In this paper, rigid dynamic modelling of cantilever with clearance was done according to the subject investigated. In the rigid dynamic modelling, clearance is equivalent to the spring-dashpot model, the impact of beam and boundary face was also taken into consideration. In ADAMS software, the dynamic simulation was carried out according to the model above. The software simulated the movement of cantilever with clearance under external excitation. Research found: When the clearance is larger, the force of impact will become larger. In order to study how the stiffness of the cantilever's supporting part influences natural frequency of the system, A Euler beam which is restricted by a draught spring and a torsion spring at its end was raised. Through numerical calculation, the relationship between natural frequency and stiffness was found. When the value of the stiffness is close to the limit value, the corresponding boundary condition is illustrated. An ADAMS experiment was carried out to check the theory and the simulation.

BAG3 facilitates the clearance of endogenous tau in primary neurons.

PubMed

Lei, Zhinian; Brizzee, Corey; Johnson, Gail V W

2015-01-01

Tau is a microtubule associated protein that is found primarily in neurons, and in pathologic conditions, such as Alzheimer's disease (AD) it accumulates and contributes to the disease process. Because tau plays a fundamental role in the pathogenesis of AD and other tauopathies, and in AD mouse models reducing tau levels improves outcomes, approaches that facilitate tau clearance are being considered as therapeutic strategies. However, fundamental to the development of such interventions is a clearer understanding of the mechanisms that regulate tau clearance. Here, we report a novel mechanism of tau degradation mediated by the co-chaperone BAG3. BAG3 has been shown to be an essential component of a complex that targets substrates to the autophagy pathway for degradation. In rat primary neurons, activation of autophagy by inhibition of proteasome activity or treatment with trehalose resulted in significant decreases in tau and phospho-tau levels. These treatments also induced an upregulation of BAG3. Proteasome inhibition activated JNK, which was responsible for the upregulation of BAG3 and increased tau clearance. Inhibiting JNK or knocking down BAG3 blocked the proteasome inhibition-induced decreases in tau. Further, BAG3 overexpression alone resulted in significant decreases in tau and phospho-tau levels in neurons. These results indicate that BAG3 plays a critical role in regulating the levels of tau in neurons, and interventions that increase BAG3 levels could provide a therapeutic approach in the treatment of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Chaos vibration of pinion and rack steering trapezoidal mechanism containing two clearances

NASA Astrophysics Data System (ADS)

Wei, Daogao; Wang, Yu; Jiang, Tong; Zheng, Sifa; Zhao, Wenjing; Pan, Zhijie

2017-08-01

The multi-clearances of breaking type steering trapezoidal mechanism joints influences vehicle steering stability. Hence, to ascertain the influence of clearance value on steering stability, this paper takes the steering mechanism of a certain vehicle type as a prototype that can be simplified into a planar six-bar linkage, then establishes the system dynamic differential equations after considering the two clearances of tie rods and the steering knuckle arms. The influence of the clearance parameters on the movement stability of the steering mechanism is studied using a numerical computation method. Results show that when the two clearances are equal, the planar movement of the tie rods changes from period-doubling to chaos as the clearances increase. When the two clearances are 0.25 mm and 1.5 mm respectively, the planar movements of the two side tie rods come into chaos, causing the steering stability to deteriorate. Moreover, with the increase of clearances, turning moment fluctuates more intensively and the peak value increases.

Calculation of tip clearance effects in a transonic compressor rotor

NASA Technical Reports Server (NTRS)

Chima, R. V.

1996-01-01

The flow through the tip clearance region of a transonic compressor rotor (NASA rotor 37) was computed and compared to aerodynamic probe and laser anemometer data. Tip clearance effects were modeled both by gridding the clearance gap and by using a simple periodicity model across the ungridded gap. The simple model was run with both the full gap height, and with half the gap height to simulate a vena-contracta effect. Comparisons between computed and measured performance maps and downstream profiles were used to validate the models and to assess the effects of gap height on the simple clearance model. Recommendations were made concerning the use of the simple clearance model. Detailed comparisons were made between the gridded clearance gap solution and the laser anemometer data near the tip at two operating points. The computer results agreed fairly well with the data but overpredicted the extent of the casing separation and underpredicted the wake decay rate. The computations were then used to describe the interaction of the tip vortex, the passage shock, and the casing boundary layer.

A Matter of Millimeters: Defining the Processes for Critical Clearances on Curiosity

NASA Technical Reports Server (NTRS)

Florow, Brandon

2013-01-01

The Mars Science Laboratory (MSL) mission presents an immense packaging problem in that it takes a rover the size of a car with a sky crane landing system and packs it tightly into a spacecraft. This creates many areas of close and critical clearances. Critical Clearances are defined as hardware-to-hardware or hardware-to-envelope clearances which fall below a pre-established location dependent threshold and pose a risk of hardware to hardware contact during events such as launch, entry, landing, and operations. Close Clearances, on the other hand, are defined as any clearance value that is chosen to be tracked but is larger than the critical clearance threshold for its region. Close clearances may be tracked for various reasons including uncertainty in design, large expected dynamic motion, etc.

Alcohol consumption decreases lactate clearance in acutely injured patients☆

PubMed Central

Dezman, Zachary D.W.; Comer, Angela C.; Narayan, Mayur; Scalea, Thomas M.; Hirshon, Jon Mark; Smith, Gordon S.

2017-01-01

Introduction Alcohol, a common risk factor for injury, has direct toxic effects on the liver. The use of lactate clearance has been well described as an indicator of the adequacy of resuscitation in injured patients. We investigated whether acutely injured patients with positive blood alcohol content (+BAC) had less lactate clearance than sober patients. Methods We conducted a retrospective cohort study of acutely injured patients treated at an urban Level 1 trauma centre between January 2010 and December 2012. Blood alcohol and venous lactate levels were measured on all patients at the time of arrival. Study subjects were patients transported directly from the scene of injury, who had an elevated lactate concentration on arrival (≥3.0 mmol/L) and at least one subsequent lactate measurement within 24 h after admission. Lactate clearance ([Lactate1 − Lactate2]/Lactate1) was calculated for all patients. Chi-squared tests were used to compare values from sober and intoxicated subjects. Lactate clearance was plotted against alcohol levels and stratified by age and Injury Severity Score (ISS). Results Serial lactate concentration measurements were obtained in 3910 patients; 1674 of them had +BAC. Patients with +BAC were younger (mean age: 36.6 [SD 14.7] vs 41.0 [SD 19.9] years [p = 0.0001]), were more often male (83.4% vs 75.9% [p = 0.0001]), had more minor injuries (ISS < 9) (33.8% vs 27.1% [p = 0.0001]), had a lower in-hospital mortality rate (1.4% vs 3.9% [p = 0.0001]), but also had lower average lactate clearance (37.8% vs 47.6% [p = 0.0001]). The lactate clearance of the sober patients (47.6 [SD 33.5]) was twice that of those with +BAC >400 (23.5 [SD 6.5]). Lactate clearance decreased with increasing BAC irrespective of age and ISS. Conclusions In a large group of acutely injured patients, a dose-dependent decrease in lactate clearance was seen in those with elevated BAC. This relationship will cause a falsely elevated lactate reading or prolong lactate

Estradiol and weight are covariates of paracetamol clearance in young women.

PubMed

Beleyn, B; Vermeersch, S; Kulo, A; Smits, A; Verbesselt, R; de Hoon, J N; Van Calsteren, K; Allegaert, K

2014-01-01

Paracetamol clearance differs between pregnant and non-pregnant women and between women with or without specific oral contraceptives (OCs). However, an association between female sex hormones and paracetamol clearance has never been explored. In total, 49 women at delivery, 8 female control subjects without OC use, historical data of 14 women taking OCs, and 15 postpartum observations with and without OCs were pooled to explore covariates of paracetamol clearance. All received a single intravenous 2-gram paracetamol dose, and blood samples were collected up to 6 h after dosing. High-performance liquid chromatography was used to quantify paracetamol. The area under the curve to time infinity (AUC0-∞) was determined and clearance (l/h·m(2)) was calculated by dose/ AUC0-∞. In addition, estradiol and progesterone were quantified by ELISA with electro-chemiluminescence. Median paracetamol clearance at delivery was significantly higher when compared to postpartum or non-pregnant women (11.9 vs. 6.42 and 8.4 l/h·m(2), at least p < 0.05), while an association between paracetamol clearance and estradiol was observed (R = 0.494, p < 0.0001). In non-pregnant subjects, there was no impact of OC exposure on paracetamol clearance. Multiple regression revealed a linear association (Radj = 0.41, p < 0.001) between paracetamol clearance and weight (p = 0.0462) and estradiol (p < 0.0001). Estradiol and weight in part explain the variation in paracetamol clearance in young women. © 2014 S. Karger AG, Basel.

32 CFR 644.521 - Limitations on clearance cost.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Limitations on clearance cost. 644.521 Section 644.521 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed...

32 CFR 644.522 - Clearance of military scrap.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of military scrap. 644.522 Section 644.522 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed...

Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice.

PubMed

Jansen, A J Gerard; Josefsson, Emma C; Rumjantseva, Viktoria; Liu, Qiyong Peter; Falet, Hervé; Bergmeier, Wolfgang; Cifuni, Stephen M; Sackstein, Robert; von Andrian, Ulrich H; Wagner, Denisa D; Hartwig, John H; Hoffmeister, Karin M

2012-02-02

When refrigerated platelets are rewarmed, they secrete active sialidases, including the lysosomal sialidase Neu1, and express surface Neu3 that remove sialic acid from platelet von Willebrand factor receptor (VWFR), specifically the GPIbα subunit. The recovery and circulation of refrigerated platelets is greatly improved by storage in the presence of inhibitors of sialidases. Desialylated VWFR is also a target for metalloproteinases (MPs), because GPIbα and GPV are cleaved from the surface of refrigerated platelets. Receptor shedding is inhibited by the MP inhibitor GM6001 and does not occur in Adam17(ΔZn/ΔZn) platelets expressing inactive ADAM17. Critically, desialylation in the absence of MP-mediated receptor shedding is sufficient to cause the rapid clearance of platelets from circulation. Desialylation of platelet VWFR therefore triggers platelet clearance and primes GPIbα and GPV for MP-dependent cleavage.

Online monitoring of dynamic tip clearance of turbine blades in high temperature environments

NASA Astrophysics Data System (ADS)

Han, Yu; Zhong, Chong; Zhu, Xiaoliang; Zhe, Jiang

2018-04-01

Minimized tip clearance reduces the gas leakage over turbine blade tips and improves the thrust and efficiency of turbomachinery. An accurate tip clearance sensor, measuring the dynamic clearances between blade tips and the turbine case, is a critical component for tip clearance control. This paper presents a robust inductive tip clearance sensor capable of monitoring dynamic tip clearances of turbine machines in high-temperature environments and at high rotational speeds. The sensor can also self-sense the temperature at a blade tip in situ such that temperature effect on tip clearance measurement can be estimated and compensated. To evaluate the sensor’s performance, the sensor was tested for measuring the tip clearances of turbine blades under various working temperatures ranging from 700 K to 1300 K and at turbine rotational speeds ranging from 3000 to 10 000 rpm. The blade tip clearance was varied from 50 to 2000 µm. The experiment results proved that the sensor can accurately measure the blade tip clearances with a temporal resolution of 10 µm. The capability of accurately measuring the tip clearances at high temperatures (~1300 K) and high turbine rotation speeds (~30 000 rpm), along with its compact size, makes it promising for online monitoring and active control of blade tip clearances of high-temperature turbomachinery.

Depressed reticuloendothelial clearance of platelets in rats after trauma.

PubMed

Kaplan, J E; Moon, D G; Minnear, F L; Saba, T M

1984-02-01

Platelet microembolization may contribute to microcirculatory and organ damage following trauma and shock. It is hypothesized that posttraumatic reticuloendothelial depression predisposes to such microembolization by failure to clear altered platelets from the circulation. The present study evaluated the short-term (1 h) clearance and organ localization of radiolabeled homologous damaged platelets in normal rats and in rats following sublethal Noble-Collip drum trauma. Platelets were collected in citrated platelet-rich plasma from normal rats and labeled with 51Cr in citrated saline. Platelets were altered by repeated centrifugation in protein-free medium. These platelets differed functionally and morphologically from normal platelets. Disappearance of iv injected damaged platelets conformed to a two-compartment exponential clearance. Velocity of clearance in the rapid compartment correlated with hepatic platelet localization, whereas velocity of clearance in the second compartment correlated with splenic platelet localization. Clearance rate of the rapid compartment was depressed at 1 h after trauma and elevated at 24 h. These changes were associated with a decrease in hepatic platelet localization at 1 h and an increase above normal at 24 h. Splenic platelet localization was decreased by 3 h following trauma. Pulmonary platelet localization was increased at all times following trauma. It is concluded that the posttrauma state is associated with a defect in the reticuloendothelial system clearance of altered platelets, which may augment embolization of platelets in the lung.

Numerical investigation of tip clearance effects on the performance of ducted propeller

NASA Astrophysics Data System (ADS)

Ding, Yongle; Song, Baowei; Wang, Peng

2015-09-01

Tip clearance loss is a limitation of the improvement of turbomachine performance. Previous studies show the Tip clearance loss is generated by the leakage flow through the tip clearance, and is roughly linearly proportional to the gap size. This study investigates the tip clearance effects on the performance of ducted propeller. The investigation was carried out by solving the Navier-Stokes equations with the commercial Computational Fluid Dynamic (CFD) code CFX14.5. These simulations were carried out to determine the underlying mechanisms of the tip clearance effects. The calculations were performed at three different chosen advance ratios. Simulation results showed that the tip loss slope was not linearly at high advance due to the reversed pressure at the leading edge. Three type of vortical structures were observed in the tip clearance at different clearance size.

32 CFR 644.517 - Clearance of Army lands.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Army lands. 644.517 Section 644.517 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed Excess Land...

Noncontact Capacitive Clearance Control System For Laser Cutting Machines

NASA Astrophysics Data System (ADS)

Topkaya, Ahmet; Schmall, Karl-Heinz; Majoli, Ralf

1989-03-01

For a continuous high quality laser cut, it is necessary among other things to position the focal point of the laser beam correctly. This means that a constant clearance between the cutting head and the workpiece with a tolerance of +/- 0.Imm must he ensured. When cutting corrugated automobile bodysheet for example, a good quality cut can only be achieved with automatic clearance control. In the following, a method of automatic clearance control is described using the assistance of a noncontact capacitive sensor system. The copper nozzle of the laser cutting head acts as the electrode of the clearance sensor. The nozzle electrode and the workpiece build a small variable capacitance depending on the clearance. A change of clearance also changes the capacitance, which in turn influences a high frequency oscillator circuit. This shift in frequency is then converted into an analogue DC signal, which can be used to operate a servo motor control for the positioning of the laser cutting head in a closed loop servo system. Laser cutting heads with clearance sensor nozzles of different shapes, suited fur most applications in the industry, with focal lengths from 2.5" to 5" have been developed. They are capable to cut metal sheet from 0.2 to 12 mm of thickness, using CO2-lasers with output power up to 2.5 kW. For special applications involving difficult workpiece topographies in automobile production applications special "trunk" nozzles have been developed. For 5-axis cutting machines and robots, new laser cutting heads with integrated nozzle sensors in combination with a high dynamic Z-axis motor drive are in a stage of development.

Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms.

PubMed

Pareja, Maria Eugenia Mansilla; Colombo, Maria I

2013-01-01

Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance.

Benefits of Improved HP Turbine Active Clearance Control

NASA Technical Reports Server (NTRS)

Ruiz, Rafael; Albers, Bob; Sak, Wojciech; Seitzer, Ken; Steinetz, Bruce M.

2007-01-01

As part of the NASA Propulsion 21 program, GE Aircraft Engines was contracted to develop an improved high pressure turbine(HPT) active clearance control (ACC) system. The system is envisioned to minimize blade tip clearances to improve HPT efficiency throughout the engine operation range simultaneously reducing fuel consumption and emissions.

Delayed clearance of triglyceride‐rich lipoproteins in young, healthy obese subjects†

PubMed Central

Goll, R.; Lekahl, S.; Moen, O. S.; Florholmen, J.

2015-01-01

Summary Obesity is associated with the metabolic syndrome. The aims were, first, to study the postprandial triglyceride clearance in young, healthy obese subjects and, second, to investigate if fasting triglycerides can predict delayed postprandial triglyceride clearance. Eighteen apparently healthy, obese subjects with no clinical signs of metabolic disturbances participated. Controls were age‐ and sex‐matched, healthy, normal weight subjects. Subclinical markers of metabolic disturbances were assessed by measuring postprandial triglycerides in serum and in chylomicrons by oral fat tolerance test. Postprandial triglyceride clearance for 8 h was assessed indirectly as removal of the lipid from serum during the oral fat tolerance test. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA‐IR). Twelve (66%) of the apparently healthy obese individuals had insulin resistance measured by HOMA‐IR. There was a delayed clearance of serum triglycerides and chylomicron triglycerides at 6 h when compared with the control group, while, at 8 h, the differences were only detected for the chylomicron triglyceride clearance. Triglyceride response was significantly greater in the obese subjects. Fasting triglycerides in upper normal level predicted a delayed postprandial triglyceride clearance and insulin resistance. In young, apparently healthy obese subjects early metabolic disturbances including insulin resistance and delayed postprandial triglyceride clearance can be detected. Fasting serum triglyceride in upper normal level predicted delayed postprandial triglyceride clearance and insulin resistance. PMID:26469529

The addition of stripes (a version of the 'horizontal-vertical illusion') increases foot clearance when crossing low-height obstacles.

PubMed

Foster, Richard J; Buckley, John G; Whitaker, David; Elliott, David B

2016-07-01

Trips over obstacles are one of the main causes of falling in older adults, with vision playing an important role in successful obstacle negotiation. We determined whether a horizontal-vertical illusion, superimposed onto low-height obstacles to create a perceived increase in obstacle height, increased foot clearances during obstacle negotiation thus reducing the likelihood of tripping. Eleven adults (mean ± 1 SD: age 27.3 ± 5.1 years) negotiated obstacles of varying heights (3, 5, 7 cm) with four different appearance conditions; two were obstacles with a horizontal-vertical illusion (vertical stripes of different thickness) superimposed on the front, one was a plain obstacle and the fourth a plain obstacle with a horizontal black line painted on the top edge. Foot clearance parameters were compared across conditions. Both illusions led to a significant increase in foot clearance when crossing the obstacle, compared to the plain condition, irrespective of obstacle height. Superimposing a horizontal-vertical illusion onto low-height obstacles can increase foot clearance, and its use on the floor section of a double-glazing door frame for example may reduce the incidence of tripping in the home. Practitioner Summary: Low-height obstacles such as the floor section of a double-glazing door frame are potential tripping hazards. In a gait lab-based study we found that a horizontal-vertical illusion superimposed onto low-height obstacles led to significantly higher foot clearances; indicating their potential as a useful safety measure.

Cleaning up the mess: cell corpse clearance in Caenorhabditis elegans.

PubMed

Pinto, Sérgio Morgado; Hengartner, Michael Otmar

2012-12-01

Genetic and cell biology studies have led to the identification in Caenorhabditis elegans of a set of evolutionary conserved cellular mechanisms responsible for the clearance of apoptotic cells. Based on the phenotype of cell corpse clearance mutants, corpse clearance can be divided into three distinct, but linked steps: corpse recognition, corpse internalization, and corpse degradation. Work in recent years has led to a better understanding of the molecular pathways that mediate each of these steps. Here, we review recent developments in our understanding of in vivo cell corpse clearance in this simple but most elegant model organism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Apoptotic Cell Clearance in Development.

PubMed

Shklover, Jeny; Levy-Adam, Flonia; Kurant, Estee

2015-01-01

Programmed cell death and its specific form apoptosis play an important role during development of multicellular organisms. They are crucial for morphogenesis and organ sculpting as well as for adjusting cell number in different systems. Removal of apoptotic cells is the last critical step of apoptosis. Apoptotic cells are properly and efficiently recognized and eliminated through phagocytosis, which is performed by professional and nonprofessional phagocytes. Phagocytosis of apoptotic cells or apoptotic cell clearance is a dynamic multistep process, involving interactions between phagocytic receptors and ligands on apoptotic cells, which are highly conserved in evolution. However, this process is extremely redundant in mammals, containing multiple factors playing similar roles in the process. Using model organisms such as Caenorhabditis elegans, Drosophila melanogaster, zebrafish, and mouse permits addressing fundamental questions in developmental cell clearance by a comprehensive approach including powerful genetics and cell biological tools enriched by live imaging. Recent studies in model organisms have enhanced significantly our understanding of the molecular and cellular basis of apoptotic cell clearance during development. Here, we review the current knowledge and illuminate the great potential of the research performed in genetic models, which opens new directions in developmental biology. © 2015 Elsevier Inc. All rights reserved.

N-linked glycan truncation causes enhanced clearance of plasma-derived von Willebrand factor.

PubMed

O'Sullivan, J M; Aguila, S; McRae, E; Ward, S E; Rawley, O; Fallon, P G; Brophy, T M; Preston, R J S; Brady, L; Sheils, O; Chion, A; O'Donnell, J S

2016-12-01

Essentials von Willebrands factor (VWF) glycosylation plays a key role in modulating in vivo clearance. VWF glycoforms were used to examine the role of specific glycan moieties in regulating clearance. Reduction in sialylation resulted in enhanced VWF clearance through asialoglycoprotein receptor. Progressive VWF N-linked glycan trimming resulted in increased macrophage-mediated clearance. Click to hear Dr Denis discuss clearance of von Willebrand factor in a free presentation from the ISTH Academy SUMMARY: Background Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD). In addition, previous studies have demonstrated that VWF glycans play a key role in regulating in vivo clearance. However, the molecular mechanisms underlying VWF clearance remain poorly understood. Objective To define the molecular mechanisms through which VWF N-linked glycan structures influence in vivo clearance. Methods By use of a series of exoglycosidases, different plasma-derived VWF (pd-VWF) glycoforms were generated. In vivo clearance of these glycoforms was then assessed in VWF -/- mice in the presence or absence of inhibitors of asialoglycoprotein receptor (ASGPR), or following clodronate-induced macrophage depletion. Results Reduced amounts of N-linked and O-linked sialylation resulted in enhanced pd-VWF clearance modulated via ASGPR. In addition to this role of terminal sialylation, we further observed that progressive N-linked glycan trimming also resulted in markedly enhanced VWF clearance. Furthermore, these additional N-linked glycan effects on clearance were ASGPR-independent, and instead involved enhanced macrophage clearance that was mediated, at least in part, through LDL receptor-related protein 1. Conclusion The carbohydrate determinants expressed on VWF regulate susceptibility to proteolysis by ADAMTS-13. In addition, our findings now further demonstrate that non-sialic acid carbohydrate

Effects of airborne pollutants on mucociliary clearance.

PubMed

Wolff, R K

1986-04-01

The mucociliary clearance system is a first line of defense against inhaled agents, and so its compromise can adversely affect health. The purpose of this paper is to provide a review of data on the effect of in vivo air pollutant exposures on the clearance of test particles from airways. Data from both animals and humans are compared whenever possible, so that estimates of human health effects may be made. Mechanisms of action are also discussed, presenting the view that for low level exposures, changes in secretions are probably responsible for most observed changes in clearance. The pollutants pertinent to this review are those that are common in the environment and most likely to have impacts on large numbers of people: sulfur oxides, sulfuric acid mist, O3, NO2, particulates, diesel exhaust, and cigarette smoke.

Novel lanthanide-labeled metal oxide nanoparticles improve the measurement of in vivo clearance and translocation.

PubMed

Abid, Aamir D; Anderson, Donald S; Das, Gautom K; Van Winkle, Laura S; Kennedy, Ian M

2013-01-10

The deposition, clearance and translocation of europium-doped gadolinium oxide nanoparticles in a mouse lung were investigated experimentally. Nanoparticles were synthesized by spray flame pyrolysis. The particle size, crystallinity and surface properties were characterized. Following instillation, the concentrations of particles in organs were determined with inductively coupled plasma mass spectrometry. The protein corona coating the nanoparticles was found to be similar to the coating on more environmentally relevant nanoparticles such as iron oxide. Measurements of the solubility of the nanoparticles in surrogates of biological fluids indicated very little propensity for dissolution, and the elemental ratio of particle constituents did not change, adding further support to the contention that intact nanoparticles were measured. The particles were intratracheally instilled into the mouse lung. After 24 hours, the target organs were harvested, acid digested and the nanoparticle mass in each organ was measured by inductively coupled plasma mass spectrometry (ICP-MS). The nanoparticles were detected in all the studied organs at low ppb levels; 59% of the particles remained in the lung. A significant amount of particles was also detected in the feces, suggesting fast clearance mechanisms. The nanoparticle system used in this work is highly suitable for quantitatively determining deposition, transport and clearance of nanoparticles from the lung, providing a quantified measure of delivered dose.

Experimental models for studying mucociliary clearance.

PubMed

King, M

1998-01-01

Respiratory tract mucus is a viscoelastic gel, the rheological properties of which are determined mainly by its content of mucous glycoproteins and water. The rheology and quantity of mucus, in concert with ciliary factors, are the major determinants of mucociliary clearance. A wide range of animal models for studying the secretion and clearance of mucus are available. Ex vivo models, such as the frog palate or excised bovine trachea, provide direct, meaningful data regarding the clearability of mucus. Rodent models of chronic bronchitis, based on irritant gas or cigarette smoke exposure, show important features of the human condition in a relatively short time. The rheological characterization of mucus is made difficult by the small quantities obtainable, particularly from normal animals. Large animal models, such as the dog or sheep, although more expensive, offer many advantages, such as the ability to carry out long-term serial measurements, and to make integrated measurements of the clearance of mucus, ciliary function, epithelial ion transport, and the rheology of mucus in the same preparation.

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

Targeted therapy using nanotechnology: focus on cancer

PubMed Central

Sanna, Vanna; Pala, Nicolino; Sechi, Mario

2014-01-01

Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication. PMID:24531078

Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice

PubMed Central

Jansen, A. J. Gerard; Josefsson, Emma C.; Rumjantseva, Viktoria; Liu, Qiyong Peter; Falet, Hervé; Bergmeier, Wolfgang; Cifuni, Stephen M.; Sackstein, Robert; von Andrian, Ulrich H.; Wagner, Denisa D.; Hartwig, John H.

2012-01-01

When refrigerated platelets are rewarmed, they secrete active sialidases, including the lysosomal sialidase Neu1, and express surface Neu3 that remove sialic acid from platelet von Willebrand factor receptor (VWFR), specifically the GPIbα subunit. The recovery and circulation of refrigerated platelets is greatly improved by storage in the presence of inhibitors of sialidases. Desialylated VWFR is also a target for metalloproteinases (MPs), because GPIbα and GPV are cleaved from the surface of refrigerated platelets. Receptor shedding is inhibited by the MP inhibitor GM6001 and does not occur in Adam17ΔZn/ΔZn platelets expressing inactive ADAM17. Critically, desialylation in the absence of MP-mediated receptor shedding is sufficient to cause the rapid clearance of platelets from circulation. Desialylation of platelet VWFR therefore triggers platelet clearance and primes GPIbα and GPV for MP-dependent cleavage. PMID:22101895

A natural human monoclonal antibody targeting Staphylococcus Protein A protects against Staphylococcus aureus bacteremia

PubMed Central

Varshney, Avanish K.; Sunley, Kevin M.; Bowling, Rodney A.; Kwan, Tzu-Yu; Mays, Heather R.; Rambhadran, Anu; Zhang, Yanfeng; Martin, Rebecca L.; Cavalier, Michael C.; Simard, John

2018-01-01

Staphylococcus aureus can cause devastating and life-threatening infections. With the increase in multidrug resistant strains, novel therapies are needed. Limited success with active and passive immunization strategies have been attributed to S. aureus immune evasion. Here, we report on a monoclonal antibody, 514G3, that circumvents a key S. aureus evasion mechanism by targeting the cell wall moiety Protein A (SpA). SpA tightly binds most subclasses of immunoglobulins via their Fc region, neutralizing effector function. The organism can thus shield itself with a protective coat of serum antibodies and render humoral immunity ineffective. The present antibody reactivity was derived from an individual with natural anti-SpA antibody titers. The monoclonal antibody is of an IgG3 subclass, which differs critically from other immunoglobulin subclasses since its Fc is not bound by SpA. Moreover, it targets a unique epitope on SpA that allows it to bind in the presence of serum antibodies. Consequently, the antibody opsonizes S. aureus and maintains effector function to enable natural immune mediated clearance. The data presented here provide evidence that 514G3 antibody is able to successfully rescue mice from S. aureus mediated bacteremia. PMID:29364906

Estimation of end point foot clearance points from inertial sensor data.

PubMed

Santhiranayagam, Braveena K; Lai, Daniel T H; Begg, Rezaul K; Palaniswami, Marimuthu

2011-01-01

Foot clearance parameters provide useful insight into tripping risks during walking. This paper proposes a technique for the estimate of key foot clearance parameters using inertial sensor (accelerometers and gyroscopes) data. Fifteen features were extracted from raw inertial sensor measurements, and a regression model was used to estimate two key foot clearance parameters: First maximum vertical clearance (m x 1) after toe-off and the Minimum Toe Clearance (MTC) of the swing foot. Comparisons are made against measurements obtained using an optoelectronic motion capture system (Optotrak), at 4 different walking speeds. General Regression Neural Networks (GRNN) were used to estimate the desired parameters from the sensor features. Eight subjects foot clearance data were examined and a Leave-one-subject-out (LOSO) method was used to select the best model. The best average Root Mean Square Errors (RMSE) across all subjects obtained using all sensor features at the maximum speed for m x 1 was 5.32 mm and for MTC was 4.04 mm. Further application of a hill-climbing feature selection technique resulted in 0.54-21.93% improvement in RMSE and required fewer input features. The results demonstrated that using raw inertial sensor data with regression models and feature selection could accurately estimate key foot clearance parameters.

High-Speed, capacitance-based tip clearance sensing

NASA Astrophysics Data System (ADS)

Haase, W. C.; Haase, Z. S.

This paper discusses recent advances in tip clearance measurement systems for turbine engines using capacitive probes. Real time measurements of individual blade pulses are generated using wideband signal processing providing 3 dB bandwidths of typically 5 MHz. Subsequent mixed-signal processing circuitry provide real-time measurements of maximum, minimum, and average clearance with latencies of one blade-to-blade time interval. Both guarded and unguarded probe configurations are possible with the system. Calibration techniques provide high accuracy measurements.

The Role of Radial Clearance on the Performance of Foil Air Bearings

NASA Technical Reports Server (NTRS)

Radil, Kevin; Howard, Samuel; Dykas, Brian

2002-01-01

Load capacity tests were conducted to determine how radial clearance variations affect the load capacity coefficient of foil air bearings. Two Generation III foil air bearings with the same design but possessing different initial radial clearances were tested at room temperature against an as-ground PS304 coated journal operating at 30,000 rpm. Increases in radial clearance were accomplished by reducing the journal's outside diameter via an in-place grinding system. From each load capacity test the bearing load capacity coefficient was calculated from the rule-of-thumb (ROT) model developed for foil air bearings. The test results indicate that, in terms of the load capacity coefficient, radial clearance has a direct impact on the performance of the foil air bearing. Each test bearing exhibited an optimum radial clearance that resulted in a maximum load capacity coefficient. Relative to this optimum value are two separate operating regimes that are governed by different modes of failure. Bearings operating with radial clearances less than the optimum exhibit load capacity coefficients that are a strong function of radial clearance and are prone to a thermal runaway failure mechanism and bearing seizure. Conversely, a bearing operating with a radial clearance twice the optimum suffered only a 20 percent decline in its maximum load capacity coefficient and did not experience any thermal management problems. However, it is unknown to what degree these changes in radial clearance had on other performance parameters, such as the stiffness and damping properties of the bearings.

48 CFR 832.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

48 CFR 32.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

48 CFR 32.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

48 CFR 832.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

48 CFR 32.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

48 CFR 832.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

48 CFR 832.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

48 CFR 32.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

Secretion clearance strategies in Australian and New Zealand Intensive Care Units.

PubMed

Ntoumenopoulos, George; Hammond, Naomi; Watts, Nicola R; Thompson, Kelly; Hanlon, Gabrielle; Paratz, Jennifer D; Thomas, Peter

2017-06-26

To describe the processes of care for secretion clearance in adult, intubated and mechanically ventilated patients in Australian and New Zealand Intensive Care Units (ICUs). A prospective, cross-sectional study was conducted through the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG) Point Prevalence Program. Forty-seven ICUs collected data from 230 patients intubated and ventilated on the study day. Secretion clearance techniques beyond standard suctioning were used in 84/230 (37%) of patients during the study period. Chest wall vibration 34/84 (40%), manual lung hyperinflation 24/84 (29%), chest wall percussion 20/84 (24%), postural drainage/patient positioning 17/84 (20%) and other techniques including mobilisation 15/84 (18%), were the most common secretion clearance techniques employed. On average (SD), patients received airway suctioning 8.8 (5.0) times during the 24-h study period. Mucus plugging events were infrequent (2.7%). The additional secretion clearance techniques were provided by physiotherapy staff in 24/47 (51%) ICUs and by both nursing and physiotherapy staff in the remaining 23/47 (49%) ICUs. One-third of intubated and ventilated patients received additional secretion clearance techniques. Mucus plugging events were infrequent with these additional secretion clearance approaches. Prospective studies must examine additional secretion clearance practices, prevalence of mucus plugging episodes and impact on patient outcomes. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Factors effective on peritoneal phosphorus transport and clearance in peritoneal dialysis patients
.

PubMed

Cebeci, Egemen; Gursu, Meltem; Uzun, Sami; Karadag, Serhat; Kazancioglu, Rumeyza; Ozturk, Savas

2017-02-01

Transport characteristics of phosphorus are different from other small solutes that are evaluated in routine peritoneal equilibration test (PET) in peritoneal dialysis (PD) patients. We aimed to evaluate peritoneal phosphorus clearance and permeability, and their relationship with peritoneal membrane transport type and creatinine clearance as well as factors affecting peritoneal phosphorus clearance. 70 adult patients on a PD program were included in our study. Phosphorus transport status was classified according to dialysate/plasma (D/P) phosphorus at the 4^th hour of PET as slow transporter (< 0.47), slow-average transporter (0.47 - 0.56), fast-average transporter (0.57 - 0.67), and fast transporter (> 0.67). We evaluated the relationship of peritoneal phosphorus clearance and transport type with PD regime, phosphorus level, and presence of residual renal function in addition to investigating factors that are effective on peritoneal phosphorus clearance. D/P phosphorus and peritoneal phosphorus clearance were positively correlated with D/P creatinine and peritoneal creatinine clearance, respectively. Automated PD and continuous ambulatory PD patients were similar regarding phosphorus and creatinine clearances and transport status based on D/P phosphorus. The major determinant of peritoneal phosphorus clearance was anuria status. Anuric patients had higher dialysate volume (11.6 ± 3.0 L vs. 8.4 ± 2.1 L, p < 0.001) and therefore higher peritoneal phosphorus clearance (61.7 ± 15.1 L/week/1.73 m² vs. 48.4 ± 14.0 L/week/1.73 m², p = 0.001). Hyperphosphatemia was present in 40% and 11% of anuric patients and those with residual renal function, respectively (p = 0.005). Peritoneal phosphorus transport characteristics are similar to that of creatinine. Although increased dialysis dose may increase peritoneal phosphorus clearance, it may be insufficient to prevent hyperphosphatemia in anuric patients.
.

HPV clearance in postpartum period of HIV-positive and negative women: a prospective follow-up study

PubMed Central

2013-01-01

Background HPV persistence is a key determinant of cervical carcinogenesis. The influence of postpartum on HPV clearance has been debated. This study aimed to assess HPV clearance in later pregnancy and postpartum among HIV-positive and negative women. Methods We conducted a follow-up study with 151 HPV-positive women coinfected with HIV, in 2007–2010. After baseline assessment, all women were retested for HPV infection using PCR in later pregnancy and after delivery. Multivariable logistic regressions assessed the putative association of covariates with HPV status in between each one of the successive visits. Results Seventy-one women (47%) have eliminated HPV between the baseline visit and their second or third visits. HIV-positive women took a significantly longer time (7.0 ± 3.8 months) to clear HPV, compared to those not infected by HIV (5.9 ± 3.0 months). HPV clearance was significantly more likely to take place after delivery than during pregnancy (84.5% x 15.5%). Conclusions Both HIV-positive and negative women presented a significant reduction in HPV infection during the postpartum period. HIV-positive status was found to be associated with a longer period of time to clear HPV infection in pregnant women. PMID:24289532

Total plasma clearance versus urinary plasma clearance of (51)Cr-EDTA in patients with cirrhosis with and without fluid retention.

PubMed

Henriksen, Ulrik L; Hansen, Hanne B; Ring-Larsen, Helmer; Bendtsen, Flemming; Henriksen, Jens H

2015-01-01

In patients with fluid retention, the total plasma clearance of (51)Cr-EDTA (ClP) may overestimate the glomerular filtration rate (GFR). The present study was therefore undertaken in order to compare ClP with the urinary plasma clearance of (51)Cr-EDTA (ClU) in patients with cirrhosis with and without fluid retention. A total of 136 patients with cirrhosis (24 without fluid retention, 112 with ascites) received a quantitative intravenous injection of (51)Cr-EDTA followed by plasma and quantitative urinary samples for 5 hours. ClP was determined from the injected dose relative to the plasma concentration-time area, extrapolated to infinity. ClU was determined as urinary excretion relative to the plasma concentration-time area up to voiding. In patients without fluid retention, the difference between ClP and ClU (ClP - ClU = ClΔ) was mean 4.5 mL/min/1.73 m(2). In patients with ascites, ClΔ was significantly higher (17.6 mL/min/1.73 m(2), p < 0.0001). ClΔ increased with lower values of GFR (r = - 0.458, p < 0.001). Repeated measurements of ClU in a subgroup of patients with fluid retention (n = 25) gave almost identical values. Different types of corrections of one-pool clearance were almost identical with ClP, except for higher clearance values, which were somewhat underestimated by the former. In patients with fluid retention and ascites ClP and corrected one-pool clearance overestimates GFR substantially. Although ClU may underestimate GFR slightly, patients with ascites should collect urine quantitatively in order to obtain a reliable measurement of GFR.

Underkeel Clearance Study.

DTIC Science & Technology

1981-09-01

EnterewJ N00014-80-C-0395 CONTENTS Page EXECUTIVE SUMMARY 1.0 INTRODUCTION 1.1 The Underlying Problem ................. 1-1 1.2 The Current Study...3-4 3.2.4 CVN Berthinq Facilities .................... 3-4 ii! JI N00014-80-C-0395 CONTENTS (continued) 3.3 Hydrologic Conditions...Drafts ...................... 3-10 3.8.3 Underkeel Clearance ........ .............. 3-10 4.0 THE ANALYSIS 4.1 The Physical Model

48 CFR 1432.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

48 CFR 1432.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

48 CFR 1432.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

48 CFR 1432.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

Acute Mucociliary Clearance Response to Aerobic Exercise in Smokers.

PubMed

Ramos, Ercy M C; Vanderlei, Luiz Carlos M; Ito, Juliana T; Lima, Fabiano F; Rodrigues, Fernanda M M; Manzano, Beatriz M; Fernandes, Rômulo A; Cecílio, Michel J; Toledo-Arruda, Alessandra C; Ramos, Dionei

2015-11-01

Mucociliary clearance is the main defense mechanism of the respiratory system, and it is influenced by several stimuli, including aerobic exercise and cigarette smoking. We evaluated the acute response of mucociliary clearance to aerobic exercise in smokers and nonsmokers compared with that found after acute smoking and smoking combined with exercise. Also, we investigated whether there was a correlation between mucociliary clearance and the autonomic nervous system under these conditions. Twenty-one smokers were evaluated for mucociliary clearance by saccharin transit time (STT), and the response of the autonomic nervous system was evaluated by heart rate variability after aerobic exercise, after exercise followed by smoking, after acute smoking, and after rest. For comparison, 17 nonsmokers were also assessed during exercise. Repeated-measures analysis of variance with the Tukey test or the Friedman test followed by the Dunn test was used to evaluate the STT, autonomic response, and other variables to exercise and/or smoking in smokers. A paired t test or Wilcoxon test was used to analyze responses to exercise in nonsmokers. Correlations were evaluated using Pearson or Spearman coefficients. The STT was reduced after exercise in both groups, with similar responses between them. Other stimuli also reduced the STT. The STT showed a negative correlation with sympathetic activity in smokers and a positive correlation with the parasympathetic system in nonsmokers. Although impaired in smokers, mucociliary clearance responded to the stimulus of exercise, as demonstrated by similar STTs compared with nonsmokers. This response was correlated with the autonomic nervous system in both groups. In smokers, mucociliary clearance also responded to the stimuli of smoking and exercise followed by smoking. Copyright © 2015 by Daedalus Enterprises.

Tear clearance implications for ocular surface health.

PubMed

de Paiva, Cintia Sade; Pflugfelder, Stephen C

2004-03-01

Tear clearance/turnover provides a global assessment of the function of the lacrimal functional unit and of tear exchange on the ocular surface. It is an indirect measure of dry eye induced inflammation on the ocular surface. It shows better correlation with the severity of ocular irritation symptoms and corneal epithelial disease in dry eye than the Schirmer 1 test. Delayed tear clearance may prove to be the best measure for identifying patients with tear film disorders who may respond to anti-inflammatory therapy.

Fiber-optic laser Doppler turbine tip clearance probe

NASA Astrophysics Data System (ADS)

Büttner, Lars; Pfister, Thorsten; Czarske, Jürgen

2006-05-01

A laser Doppler based method for in situ single blade tip clearance measurements of turbomachines with high precision is presented for what we believe is the first time. The sensor is based on two superposed fanlike interference fringe systems generated by two laser wavelengths from a fiber-coupled, passive, and therefore compact measurement head employing diffractive optics. Tip clearance measurements at a transonic centrifugal compressor performed during operation at 50,000 rpm (833 Hz, 586 m/s tip speed) are reported. At these speeds the measured uncertainty of the tip position was less than 20 μm, a factor of 2 more accurate than that of capacitive probes. The sensor offers great potential for in situ and online high-precision tip clearance measurements of metallic and nonmetallic turbine blades.

Fiber-optic laser Doppler turbine tip clearance probe.

PubMed

Büttner, Lars; Pfister, Thorsten; Czarske, Jürgen

2006-05-01

A laser Doppler based method for in situ single blade tip clearance measurements of turbomachines with high precision is presented for what we believe is the first time. The sensor is based on two superposed fanlike interference fringe systems generated by two laser wavelengths from a fiber-coupled, passive, and therefore compact measurement head employing diffractive optics. Tip clearance measurements at a transonic centrifugal compressor performed during operation at 50,000 rpm (833 Hz, 586 m/s tip speed) are reported. At these speeds the measured uncertainty of the tip position was less than 20 microm, a factor of 2 more accurate than that of capacitive probes. The sensor offers great potential for in situ and online high-precision tip clearance measurements of metallic and nonmetallic turbine blades.

CF6 Jet Engine Diagnostics Program: High pressure compressor clearance investigation

NASA Technical Reports Server (NTRS)

Radomski, M. A.

1982-01-01

The effects of high pressure compressor clearance changes on engine performance were experimentally determined on a CF6 core engine. The results indicate that a one percent reduction in normalized average clearance, expressed as a fraction of airfoil length, improves compressor efficiency by one percent. Compressor clearances are reduced by the application of rotor bore cooling, insulation of the stator casing, and use of a low coefficient of expansion material in the aft stages. This improvement amounts to a reduction of normalized average clearance of 0.78 percent, relative to CF6-60 compressor, which is equivalent to an improvement in compressor efficiency of 0.78 percent.

Effect of isolated hepatic ischemia on organic anion clearance and oxidative metabolism.

PubMed

Minard, G; Bynoe, R; Wood, G C; Fabian, T C; Croce, M; Kudsk, K A

1992-04-01

Hepatic failure is frequently seen following severe hemorrhagic shock, sepsis, and trauma. Clearance of various drugs has been used to evaluate hepatocellular dysfunction, including indocyanine green (ICG), an organic anionic dye that is transported similarly to bilirubin, and antipyrine (AP), a marker of oxidative phosphorylation. Previous investigators have noted a decrease in ICG excretion following systemic hemorrhage. The effect of isolated hepatic ischemia on the clearances of ICG and AP was studied in 16 pigs after 90 minutes of vascular occlusion to the liver. Antipyrine clearance decreased almost 50% from baseline values at 24 and 72 hours after the ischemia procedure, indicating a significant depression in the cytochrome P-450 system. On the other hand, ICG clearance did not change significantly. In conclusion, ICG clearance is not depressed after isolated hepatic ischemia in pigs. Changes in organic anion clearance after systemic hemorrhage may be because of release of toxic products from ischemic peripheral tissue.

49 CFR 392.12 - Highway-rail crossings; safe clearance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 5 2013-10-01 2013-10-01 false Highway-rail crossings; safe clearance. 392.12... DRIVING OF COMMERCIAL MOTOR VEHICLES Driving of Commercial Motor Vehicles § 392.12 Highway-rail crossings; safe clearance. No driver of a commercial motor vehicle shall drive onto a highway-rail grade crossing...

49 CFR 392.12 - Highway-rail crossings; safe clearance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 5 2014-10-01 2014-10-01 false Highway-rail crossings; safe clearance. 392.12... DRIVING OF COMMERCIAL MOTOR VEHICLES Driving of Commercial Motor Vehicles § 392.12 Highway-rail crossings; safe clearance. No driver of a commercial motor vehicle shall drive onto a highway-rail grade crossing...

76 FR 17615 - Highway-Rail Grade Crossing; Safe Clearance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-30

...-2006-25660] RIN 2137-AE69 & 2126-AB04 Highway-Rail Grade Crossing; Safe Clearance AGENCY: Pipeline and... PHMSA and FMCSA extend the comment period for the Highway-Rail Grade Crossing; Safe Clearance Notice of... Alliance (CVSA) requested that PHMSA and FMCSA extend the comment period for the Highway-Rail Grade...

48 CFR 832.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 832.502-2 Contract finance office clearance. Contracting...

48 CFR 32.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 32.502-2 Contract finance office clearance. The contracting...

14 CFR 29.411 - Ground clearance: tail rotor guard.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

14 CFR 27.411 - Ground clearance: tail rotor guard.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

14 CFR 27.411 - Ground clearance: tail rotor guard.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

14 CFR 29.411 - Ground clearance: tail rotor guard.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

32 CFR 644.516 - Clearance of Air Force lands.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Air Force lands. 644.516 Section 644... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological contaminants...

48 CFR 1432.502-2 - Contract finance office clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 1432.502-2 Contract finance office clearance. The CO shall...

31 CFR 205.20 - What is a clearance pattern?

Code of Federal Regulations, 2010 CFR

2010-07-01

..., unless additional data is required to accurately represent the flow of Federal funds. (e) If a State uses... FEDERAL-STATE FUNDS TRANSFERS Rules Applicable to Federal Assistance Programs Included in a Treasury-State Agreement § 205.20 What is a clearance pattern? States use clearance patterns to project when funds are paid...

Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis.

PubMed

Hasani, A; Chapman, T H; McCool, D; Smith, R E; Dilworth, J P; Agnew, J E

2008-01-01

Inspired air humidification has been reported to show some benefit in bronchiectatic patients. We have investigated the possibility that one effect might be to enhance mucociliary clearance. Such enhancement might, if it occurs, help to lessen the risks of recurrent infective episodes. Using a radioaerosol technique, we measured lung mucociliary clearance before and after 7 days of domiciliary humidification. Patients inhaled high flow saturated air at 37 degrees C via a patient-operated humidification nasal inhalation system for 3 h per day. We assessed tracheobronchial mucociliary clearance from the retention of (99m)Tc-labelled polystyrene tracer particles monitored for 6 h, with a follow-up 24-h reading. Ten out of 14 initially recruited patients (age 37-75 years; seven females) completed the study (two withdrew after their initial screening and two prior to the initial clearance test). Seven patients studied were non-smokers; three were ex-smokers (1-9 pack-years). Initial tracer radioaerosol distribution was closely similar between pre- and post-treatment. Following humidification, lung mucociliary clearance significantly improved, the area under the tracheobronchial retention curve decreased from 319 +/- 50 to 271 +/- 46%h (p < 0.07). Warm air humidification treatment improved lung mucociliary clearance in our bronchiectatic patients. Given this finding plus increasing laboratory and clinical interest in humidification mechanisms and effects, we believe further clinical trials of humidification therapy are desirable, coupled with analysis of humidification effects on mucus properties and transport.

48 CFR 245.7101-4 - DD Form 1640, Request for Plant Clearance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 1640, Request for Plant Clearance. 245.7101-4 Section 245.7101-4 Federal Acquisition Regulations System DEFENSE... Forms 245.7101-4 DD Form 1640, Request for Plant Clearance. Use to request plant clearance assistance or...

Site clearance working group

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The Gulf of Mexico and Louisiana continue to be areas with a high level of facility removal, and the pace of removal is projected to increase. Regulations were promulgated for the Gulf of Mexico and Louisiana requiring that abandoned sites be cleared of debris that could interfere with fishing and shrimping activities. The site clearance regulations also required verification that the sites were clear. Additionally, government programs were established to compensate fishermen for losses associated with snagging their equipment on oil and gas related objects that remained on the water bottoms in areas other than active producing sites and sitesmore » that had been verified as clear of obstructions and snags. The oil and gas industry funds the compensation programs. This paper reviews the regulations and evolving operating practices in the Gulf of Mexico and Louisiana where site clearance and fisherman`s gear compensation regulations have been in place for a number of years. Although regulations and guidelines may be in place elsewhere in the world, this paper focuses on the Gulf of Mexico and Louisiana. Workshop participants are encouraged to bring up international issues during the course of the workshop. Additionally, this paper raises questions and focuses on issues that are of concern to the various Gulf of Mexico and Louisiana water surface and water bottom stakeholders. This paper does not have answers to the questions or issues. During the workshop participants will debate the questions and issues in an attempt to develop consensus opinions and/or make suggestions that can be provided to the appropriate organizations, both private and government, for possible future research or policy adjustments. Site clearance and facility removal are different activities. Facility removal deals with removal of the structures used to produce oil and gas including platforms, wells, casing, piles, pipelines, well protection structures, etc.« less

Enzyme-inducing anticonvulsants increase plasma clearance of dexmedetomidine: a pharmacokinetic and pharmacodynamic study.

PubMed

Flexman, Alana M; Wong, Harvey; Riggs, K Wayne; Shih, Tina; Garcia, Paul A; Vacas, Susana; Talke, Pekka O

2014-05-01

Dexmedetomidine is useful during mapping of epileptic foci as it facilitates electrocorticography unlike most other anesthetic agents. Patients with seizure disorders taking enzyme-inducing anticonvulsants appear to be resistant to its sedative effects. The objective of the study was to compare the pharmacokinetic and pharmacodynamic profile of dexmedetomidine in healthy volunteers with volunteers with seizure disorders receiving enzyme-inducing anticonvulsant medications. Dexmedetomidine was administered using a step-wise, computer-controlled infusion to healthy volunteers (n = 8) and volunteers with seizure disorders (n = 8) taking phenytoin or carbamazapine. Sedation and dexmedetomidine plasma levels were assessed at baseline, during the infusion steps, and after discontinuation of the infusion. Sedation was assessed by using the Observer's Assessment of Alertness/Sedation Scale, Ramsay Sedation Scale, and Visual Analog Scale and processed electroencephalography (entropy) monitoring. Pharmacokinetic analysis was performed on both groups, and differences between groups were determined using the standard two-stage approach. A two-compartment model was fit to dexmedetomidine concentration-time data. Dexmedetomidine plasma clearance was 43% higher in the seizure group compared with the control group (42.7 vs. 29.9 l/h; P = 0.007). In contrast, distributional clearance and the volume of distribution of the central and peripheral compartments were similar between the groups. No difference in sedation was detected between the two groups during a controlled range of target plasma concentrations. This study demonstrates that subjects with seizure disorders taking enzyme-inducing anticonvulsant medications have an increased plasma clearance of dexmedetomidine as compared with healthy control subjects.

20 CFR 655.150 - Interstate clearance of job order.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

20 CFR 655.150 - Interstate clearance of job order.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

20 CFR 655.150 - Interstate clearance of job order.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

20 CFR 655.150 - Interstate clearance of job order.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

20 CFR 655.150 - Interstate clearance of job order.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

HPT Clearance Control: Intelligent Engine Systems-Phase 1

NASA Technical Reports Server (NTRS)

2005-01-01

The following work has been completed to satisfy the Phase I Deliverables for the "HPT Clearance Control" project under NASA GRC's "Intelligent Engine Systems" program: (1) Need for the development of an advanced HPT ACC system has been very clearly laid out, (2) Several existing and potential clearance control systems have been reviewed, (3) A scorecard has been developed to document the system, performance (fuel burn, range, payload, etc.), thermal, and mechanical characteristics of the existing clearance control systems, (4) Engine size and flight cycle selection for the advanced HPT ACC system has been reviewed with "large engine"/"long range mission" combination showing the most benefit, (5) A scoring criteria has been developed to tie together performance parameters for an objective, data driven comparison of competing systems, and (6) The existing HPT ACC systems have been scored based on this scoring system.

Treatment of resistant tattoos using a new generation Q-switched Nd:YAG laser: influence of beam profile and spot size on clearance success.

PubMed

Karsai, Syrus; Pfirrmann, Gudrun; Hammes, Stefan; Raulin, Christian

2008-02-01

Multiple treatments of resistant tattoos often result in fibrosis and visible textural changes that lessen response to subsequent treatments. The aim of this study is to evaluate the influence of beam profile and spot size on clearance rates and side effects in the setting of resistant tattoos. Thirty-six professional, black tattoos (32 patients) were treated unsuccessfully with a Q-switched Nd:YAG laser (MedLite C3, HoyaConBio Inc., Fremont, CA). Because of therapy resistance all tattoos were re-treated using a new generation Nd:YAG laser (MedLite C6, HoyaConBio Inc.). Maximum energy fluence (E (max)), mean energy fluence, mean spot size, level of clearance, side effects and beam profile (irradiance distribution) of both laser systems were assessed and evaluated in a retrospective study. All tattoos were previously treated with the C3 laser at 1,064 nm using a mean E(max) of 5.8+/-0.8 J/cm(2) (range 3.8-7.5 J/cm(2)) as compared with a mean E(max) of 6.4+/-1.6 J/cm(2) (range 3.2-9.0 J/cm(2)) during the C6 treatment course. Corresponding spot sizes were larger during C6 treatments as compared with C3 (5.0+/-0.9 and 3.6+/-0.2 mm, respectively). The C6 laser had a "flat top" and homogenous profile regardless of the spot size. For the C3 laser the beam shape was "Gaussian," and the homogeneity was reduced by numerous micro-spikes and micro-nadirs. After the C6 treatment course 33.3% of the tattoos showed clearance of grade 1 (0-25%), 16.7% of grade 2 (26-50%), 16.7% of grade 3 (51-75%), 30.5% of grade 4 (76-95%), 2.8% of grade 5 (96-100%). The total rate of side effects due to C6 treatment was 8.3% in all tattoos (hyperpigmentation 5.6%, hypopigmentation 2.7%, textural changes/scars 0%). This clinical study documents for the first time the impact of a 1,064-nm Nd:YAG laser with a more homogenous beam profile and a larger spot size on the management of resistant tattoos. Only a few treatment sessions were necessary to achieve an additional clearance with a low rate of

Genome-wide study of methotrexate clearance replicates SLCO1B1

PubMed Central

Ramsey, Laura B.; Panetta, John C.; Smith, Colton; Yang, Wenjian; Fan, Yiping; Winick, Naomi J.; Martin, Paul L.; Cheng, Cheng; Devidas, Meenakshi; Pui, Ching-Hon; Evans, William E.; Hunger, Stephen P.; Loh, Mignon

2013-01-01

Methotrexate clearance can influence the cure of and toxicity in children with acute lymphoblastic leukemia (ALL). We estimated methotrexate plasma clearance for 1279 patients with ALL treated with methotrexate (24-hour infusion of a 1 g/m2 dose or 4-hour infusion of a 2 g/m2 dose) on the Children's Oncology Group P9904 and P9905 protocols. Methotrexate clearance was lower in older children (P = 7 × 10−7), girls (P = 2.7 × 10−4), and those who received a delayed-intensification phase (P = .0022). A genome-wide analysis showed that methotrexate clearance was associated with polymorphisms in the organic anion transporter gene SLCO1B1 (P = 2.1 × 10−11). This replicates findings using different schedules of high-dose methotrexate in St Jude ALL treatment protocols; a combined meta-analysis yields a P value of 5.7 × 10−19 for the association of methotrexate clearance with SLCO1B1 SNP rs4149056. Validation of this variant with 5 different treatment regimens of methotrexate solidifies the robustness of this pharmacogenomic determinant of methotrexate clearance. This study is registered at http://www.clinicaltrials.gov as NCT00005585 and NCT00005596. PMID:23233662

HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal

PubMed Central

Wu, Guoxin; Swanson, Michael; Talla, Aarthi; Graham, Donald; Strizki, Julie; Gorman, Daniel; Barnard, Richard J.O.; Blair, Wade; Søgaard, Ole S.; Tolstrup, Martin; Østergaard, Lars; Rasmussen, Thomas A.; Sekaly, Rafick-Pierre; Archin, Nancie M.; Hazuda, Daria J.; Howell, Bonnie J.

2017-01-01

Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs. Importantly, we demonstrate that clinical administration of histone deacetylase inhibitors (HDACis; vorinostat and panobinostat) induced HIV gag p24, and ex vivo stimulation produced sufficient viral antigen to elicit immune-mediated cell killing using anti-gp120/CD3 bispecific antibody. These findings extend beyond classical nucleic acid endpoints, which are confounded by the predominance of mutated, defective proviruses and, of paramount importance, enable assessment of cells making HIV protein that can now be targeted by immunological approaches. PMID:28814661

Inert gas clearance from tissue by co-currently and counter-currently arranged microvessels

PubMed Central

Lu, Y.; Michel, C. C.

2012-01-01

To elucidate the clearance of dissolved inert gas from tissues, we have developed numerical models of gas transport in a cylindrical block of tissue supplied by one or two capillaries. With two capillaries, attention is given to the effects of co-current and counter-current flow on tissue gas clearance. Clearance by counter-current flow is compared with clearance by a single capillary or by two co-currently arranged capillaries. Effects of the blood velocity, solubility, and diffusivity of the gas in the tissue are investigated using parameters with physiological values. It is found that under the conditions investigated, almost identical clearances are achieved by a single capillary as by a co-current pair when the total flow per tissue volume in each unit is the same (i.e., flow velocity in the single capillary is twice that in each co-current vessel). For both co-current and counter-current arrangements, approximate linear relations exist between the tissue gas clearance rate and tissue blood perfusion rate. However, the counter-current arrangement of capillaries results in less-efficient clearance of the inert gas from tissues. Furthermore, this difference in efficiency increases at higher blood flow rates. At a given blood flow, the simple conduction-capacitance model, which has been used to estimate tissue blood perfusion rate from inert gas clearance, underestimates gas clearance rates predicted by the numerical models for single vessel or for two vessels with co-current flow. This difference is accounted for in discussion, which also considers the choice of parameters and possible effects of microvascular architecture on the interpretation of tissue inert gas clearance. PMID:22604885

Analysis of foot clearance in firefighters during ascent and descent of stairs.

PubMed

Kesler, Richard M; Horn, Gavin P; Rosengren, Karl S; Hsiao-Wecksler, Elizabeth T

2016-01-01

Slips, trips, and falls are a leading cause of injury to firefighters with many injuries occurring while traversing stairs, possibly exaggerated by acute fatigue from firefighting activities and/or asymmetric load carriage. This study examined the effects that fatigue, induced by simulated firefighting activities, and hose load carriage have on foot clearance while traversing stairs. Landing and passing foot clearances for each stair during ascent and descent of a short staircase were investigated. Clearances decreased significantly (p < 0.05) post-exercise for nine of 12 ascent parameters and increased for two of eight descent parameters. Load carriage resulted in significantly decreased (p < 0.05) clearance over three ascent parameters, and one increase during descent. Decreased clearances during ascent caused by fatigue or load carriage may result in an increased trip risk. Increased clearances during descent may suggest use of a compensation strategy to ensure stair clearance or an increased risk of over-stepping during descent. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

7 CFR 1927.53 - Costs of title clearance and closing of transactions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Costs of title clearance and closing of transactions... and Loan Closing § 1927.53 Costs of title clearance and closing of transactions. The borrower or the... payment of all costs of title clearance and closing of the transaction and will arrange for payment before...

76 FR 17182 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... Activities: Proposed Collection; Comment Request; Generic Clearance for the Collection of Qualitative... Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service...: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery. Abstract...

76 FR 19359 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery AGENCY... Information Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback...: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery. Abstract...

Railway Tunnel Clearance Inspection Method Based on 3D Point Cloud from Mobile Laser Scanning

PubMed Central

Zhou, Yuhui; Wang, Shaohua; Mei, Xi; Yin, Wangling; Lin, Chunfeng; Mao, Qingzhou

2017-01-01

Railway tunnel clearance is directly related to the safe operation of trains and upgrading of freight capacity. As more and more railway are put into operation and the operation is continuously becoming faster, the railway tunnel clearance inspection should be more precise and efficient. In view of the problems existing in traditional tunnel clearance inspection methods, such as low density, slow speed and a lot of manual operations, this paper proposes a tunnel clearance inspection approach based on 3D point clouds obtained by a mobile laser scanning system (MLS). First, a dynamic coordinate system for railway tunnel clearance inspection has been proposed. A rail line extraction algorithm based on 3D linear fitting is implemented from the segmented point cloud to establish a dynamic clearance coordinate system. Second, a method to seamlessly connect all rail segments based on the railway clearance restrictions, and a seamless rail alignment is formed sequentially from the middle tunnel section to both ends. Finally, based on the rail alignment and the track clearance coordinate system, different types of clearance frames are introduced for intrusion operation with the tunnel section to realize the tunnel clearance inspection. By taking the Shuanghekou Tunnel of the Chengdu–Kunming Railway as an example, when the clearance inspection is carried out by the method mentioned herein, its precision can reach 0.03 m, and difference types of clearances can be effectively calculated. This method has a wide application prospects. PMID:28880232

Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of 64Cu-Au alloy nanoclusters

NASA Astrophysics Data System (ADS)

Zhao, Yongfeng; Sultan, Deborah; Detering, Lisa; Luehmann, Hannah; Liu, Yongjian

2014-10-01

Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs.Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal

Clearance of the cervical spine in clinically unevaluable trauma patients.

PubMed

Halpern, Casey H; Milby, Andrew H; Guo, Wensheng; Schuster, James M; Gracias, Vicente H; Stein, Sherman C

2010-08-15

Meta-analytic costeffectiveness analysis. Our goal was to compare the results of different management strategies for trauma patients in whom the cervical spine was not clinically evaluable due to impaired consciousness, endotracheal intubation, or painful distracting injuries. We performed a structured literature review related to cervical spine trauma, radiographic clearance techniques (plain radiography, flexion/extension, CT, and MRI), and complications associated with semirigid collar use. Meta-analytic techniques were used to pool data from multiple sources to calculate pooled mean estimates of sensitivities and specificities of imaging techniques for cervical spinal clearance, rates of complications from various clearance strategies and from empirical use of semirigid collars. A decision analysis model was used to compare outcomes and costs among these strategies. Slightly more than 7.5% of patients who are clinically unevaluable have cervical spine injuries, and 42% of these injuries are associated with spinal instability. Sensitivity of plain radiography or fluoroscopy for spinal clearance was 57% (95% CI: 57%-60%). Sensitivities for CT and MRI alone were 83% (82%-84%) and 87% (84%-89%), respectively. Complications associated with collar use ranged from 1.3% (2 days) to 7.1% (10 days) but were usually minor and short-lived. Quadriplegia resulting from spinal instability missed by a clearance test had enormous impacts on longevity, quality of life, and costs. These impacts overshadowed the effects of prolonged collar application, even when the incidence of quadriplegia was extremely low. As currently used, neuroimaging studies for cervical spinal clearance in clinically unevaluable patients are not cost-effective compared with empirical immobilization in a semirigid collar.

76 FR 55078 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-06

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76 FR 39893 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

...; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery... (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery.... SUPPLEMENTARY INFORMATION: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service...

Shape memory alloy adaptive control of gas turbine engine compressor blade tip clearance

NASA Astrophysics Data System (ADS)

Schetky, Lawrence M.; Steinetz, Bruce M.

1998-06-01

The ambient air ingested through the inlet of a gas turbine is first compressed by an axial compressor followed by further compression in a centrifugal compressor and then fed into the combustion chamber where ignition and expansion take place to produce the engine thrust. The axial compressor typically has five or more stages which consist of revolving blades and stators and the overall performance of the turbine is strongly affected by the compressor efficiency. When the turbine is turned on, to accommodate the rapid initial increase in the compressor blade length due to centrifugal force, the cold turbine has a built in clearance between the turbine blade tip and the casing. As the turbine reached its operating temperature there is a further increase in the blade length due to thermal expansion and, at the same time, the diameter of the casing increases. The net result is that when these various components have reached their equilibrium temperatures, the initial cold build clearance is reduced, but there remains a residual clearance. The magnitude of this clearance has a direct effect on the compressor efficiency and can be stated as: Δη/Δ CLR equals 0.5 where η is efficiency and CLR is the tip clearance. The concept of adaptive tip clearance control is based on the ability of a shape memory alloy ring to shrink to a predetermined diameter when heated to the temperature of a particular stage, and thus reducing the tip clearance. The ring is fabricated from a CuAlNi shape memory alloy and is mounted in the casing so as to be coaxial with the rotating blades of the particular stage. When cold, the ring dimensions are such as to provide the required cold build clearance, but when at operating temperature the reduced diameter creates a very small tip clearance. The clearance provided by this concept is much smaller than the clearance normally obtained for a turbine of the size being studied.

Effect of Internal Clearance on Load Distribution and Life of Radially Loaded Ball and Roller Bearings

NASA Technical Reports Server (NTRS)

Oswald, Fred B.; Zaretsky, Erwin V.; Poplawski, Joseph V.

2012-01-01

The effect of internal clearance on radially loaded deepgroove ball and cylindrical roller bearing load distribution and fatigue life was determined for four clearance groups defined in the bearing standards. The analysis was extended to negative clearance (interference) conditions to produce a curve of life factor versus internal clearance. Rolling-element loads can be optimized and bearing life maximized for a small negative operating clearance. Life declines gradually with positive clearance and rapidly with increasing negative clearance. Relationships were found between bearing life and internal clearance as a function of ball or roller diameter, adjusted for load. Results are presented as life factors for radially loaded bearings independent of bearing size or applied load. In addition, a modified Stribeck Equation is presented that relates the maximum rolling-element load to internal bearing clearance.

Analysis of phase II studies on targeted agents and subsequent phase III trials: what are the predictors for success?

PubMed

Chan, John K; Ueda, Stefanie M; Sugiyama, Valerie E; Stave, Christopher D; Shin, Jacob Y; Monk, Bradley J; Sikic, Branimir I; Osann, Kathryn; Kapp, Daniel S

2008-03-20

To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors. We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models. Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial. In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.

76 FR 10626 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-25

... Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery AGENCY... Clearance for the Collection of Qualitative Feedback on Agency Service Delivery'' to OMB for approval under...: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery. Abstract...

Preliminary Diffusive Clearance of Silicon Nanopore Membranes in a Parallel Plate Configuration for Renal Replacement Therapy

PubMed Central

Kim, Steven; Heller, James; Iqbal, Zohora; Kant, Rishi; Kim, Eun Jung; Durack, Jeremy; Saeed, Maythem; Do, Loi; Hetts, Steven; Wilson, Mark; Brakeman, Paul; Fissell, William H.; Roy, Shuvo

2015-01-01

Silicon nanopore membranes (SNM) with compact geometry and uniform pore size distribution have demonstrated a remarkable capacity for hemofiltration. These advantages could potentially be used for hemodialysis. Here we present an initial evaluation of the SNM’s mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. Mechanical robustness of the SNM was demonstrated by exposing membranes to high flows (200ml/min) and pressures (1,448mmHg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4-hours in an extra-corporeal porcine model. The pressure drop across the flow cell was 4.6mmHg at 200ml/min. Mechanical testing showed that SNM could withstand up to 775.7mmHg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extra-corporeal studies showed blood was successfully driven via the arterial-venous pressure differential without thrombus formation. Bare silicon showed increased cell adhesion with a 4.1 fold increase and 1.8 fold increase over polyethylene-glycol (PEG)-coated surfaces for tissue plasminogen factor (t-PA) and platelet adhesion (CD-41), respectively. These initial results warrant further design and development of a fully scaled SNM-based parallel plate dialyzer for renal replacement therapy. PMID:26692401

Is the gravity effect of radiographic anatomic features enough to justify stone clearance or fragments retention following extracorporeal shock wave lithotripsy (SWL).

PubMed

Mustafa, Mahmoud

2012-08-01

We determined whether the gravity effect of radiographic anatomic features on the preoperative urography (IVP) are enough to predict fragments clearance after shock wave lithotripsy (SWL). A Total of 282 patients with mean age 45.8 ± 13.2 years (189 male, 93 female), who underwent SWL due to renal calculi between October 2005 and August 2009 were enrolled. The mean calculi load was 155.72 ± 127.66 mm². The patients were stratified into three groups: patients with pelvis calculi (group 1); patients with upper or middle pole calculi (group 2) and patients with lower pole calculi (group 3). Three angles on the pretreatment IVP were measured: the inner angle between the axis of the lower pole infundibular and ureteropelvic axis (angle I); the inner angle between the lower pole infundibular axis and main axis of pelvis-ureteropelvic (UP) junction point (angle II) and the inner angle between the lower pole infundibular axis and perpendicular line (angle III). Multivariate analysis was used to define the significant predictors of stone clearance. The overall success rate was 85.81%. All angles, sessions number, shock waves number and stone burden were significant predictors of success in patients in group 1. However, in group 2 only angle II and in group 3 angles I and II had significant effect on stone clearance. Radiographic anatomic features have significant role in determining the stone-free rate following satisfactory fragmentation of renal stones with SWL. The measurement of infundibulopelvic angle in different manner helps to predict the stone-free status in patients with renal calculi located not only in lower pole, but also in renal pelvis and upper or middle pole. Gravity effect is not enough to justify the significant influence of the radiographic anatomic features on the stone clearance and fragments retention after SWL.

CO2 clearance by membrane lungs.

PubMed

Sun, Liqun; Kaesler, Andreas; Fernando, Piyumindri; Thompson, Alex J; Toomasian, John M; Bartlett, Robert H

2018-05-01

Commercial membrane lungs are designed to transfer a specific amount of oxygen per unit of venous blood flow. Membrane lungs are much more efficient at removing CO 2 than adding oxygen, but the range of CO 2 transfer is rarely reported. Commercial membrane lungs were studied with the goal of evaluating CO 2 removal capacity. CO 2 removal was measured in 4 commercial membrane lungs under standardized conditions. CO 2 clearance can be greater than 4 times that of oxygen at a given blood flow when the gas to blood flow ratio is elevated to 4:1 or 8:1. The CO 2 clearance was less dependent on surface area and configuration than oxygen transfer. Any ECMO system can be used for selective CO 2 removal.

Nanomedicine strategies for sustained, controlled, and targeted treatment of cancer stem cells of the digestive system.

PubMed

Xie, Fang-Yuan; Xu, Wei-Heng; Yin, Chuan; Zhang, Guo-Qing; Zhong, Yan-Qiang; Gao, Jie

2016-10-15

Cancer stem cells (CSCs) constitute a small proportion of the cancer cells that have self-renewal capacity and tumor-initiating ability. They have been identified in a variety of tumors, including tumors of the digestive system. CSCs exhibit some unique characteristics, which are responsible for cancer metastasis and recurrence. Consequently, the development of effective therapeutic strategies against CSCs plays a key role in increasing the efficacy of cancer therapy. Several potential approaches to target CSCs of the digestive system have been explored, including targeting CSC surface markers and signaling pathways, inducing the differentiation of CSCs, altering the tumor microenvironment or niche, and inhibiting ATP-driven efflux transporters. However, conventional therapies may not successfully eradicate CSCs owing to various problems, including poor solubility, stability, rapid clearance, poor cellular uptake, and unacceptable cytotoxicity. Nanomedicine strategies, which include drug, gene, targeted, and combinational delivery, could solve these problems and significantly improve the therapeutic index. This review briefly summarizes the ongoing development of strategies and nanomedicine-based therapies against CSCs of the digestive system.

Nanomedicine strategies for sustained, controlled, and targeted treatment of cancer stem cells of the digestive system

PubMed Central

Xie, Fang-Yuan; Xu, Wei-Heng; Yin, Chuan; Zhang, Guo-Qing; Zhong, Yan-Qiang; Gao, Jie

2016-01-01

Cancer stem cells (CSCs) constitute a small proportion of the cancer cells that have self-renewal capacity and tumor-initiating ability. They have been identified in a variety of tumors, including tumors of the digestive system. CSCs exhibit some unique characteristics, which are responsible for cancer metastasis and recurrence. Consequently, the development of effective therapeutic strategies against CSCs plays a key role in increasing the efficacy of cancer therapy. Several potential approaches to target CSCs of the digestive system have been explored, including targeting CSC surface markers and signaling pathways, inducing the differentiation of CSCs, altering the tumor microenvironment or niche, and inhibiting ATP-driven efflux transporters. However, conventional therapies may not successfully eradicate CSCs owing to various problems, including poor solubility, stability, rapid clearance, poor cellular uptake, and unacceptable cytotoxicity. Nanomedicine strategies, which include drug, gene, targeted, and combinational delivery, could solve these problems and significantly improve the therapeutic index. This review briefly summarizes the ongoing development of strategies and nanomedicine-based therapies against CSCs of the digestive system. PMID:27795813

Long-term clearance from small airways in subjects with ciliary dysfunction.

PubMed

Lindström, Maria; Falk, Rolf; Hjelte, Lena; Philipson, Klas; Svartengren, Magnus

2006-05-20

The objective of this study was to investigate if long-term clearance from small airways is dependent on normal ciliary function. Six young adults with primary ciliary dyskinesia (PCD) inhaled 111 Indium labelled Teflon particles of 4.2 microm geometric and 6.2 microm aerodynamic diameter with an extremely slow inhalation flow, 0.05 L/s. The inhalation method deposits particles mainly in the small conducting airways. Lung retention was measured immediately after inhalation and at four occasions up to 21 days after inhalation. Results were compared with data from ten healthy controls. For additional comparison three of the PCD subjects also inhaled the test particles with normal inhalation flow, 0.5 L/s, providing a more central deposition. The lung retention at 24 h in % of lung deposition (Ret24) was higher (p < 0.001) in the PCD subjects, 79 % (95% Confidence Interval, 67.6;90.6), compared to 49% (42.3;55.5) in the healthy controls. There was a significant clearance after 24 h both in the PCD subjects and in the healthy controls with equivalent clearance. The mean Ret24 with slow inhalation flow was 73.9 +/- 1.9% compared to 68.9 +/- 7.5% with normal inhalation flow in the three PCD subjects exposed twice. During day 7-21 the three PCD subjects exposed twice cleared 9% with normal flow, probably representing predominantly alveolar clearance, compared to 19% with slow inhalation flow, probably representing mainly small airway clearance. This study shows that despite ciliary dysfunction, clearance continues in the small airways beyond 24 h. There are apparently additional clearance mechanisms present in the small airways.

Predictive factors of spontaneous CMV DNAemia clearance in kidney transplantation.

PubMed

Noble, Johan; Gatault, Philippe; Sautenet, Bénédicte; Gaudy-Graffin, Catherine; Beby-Defaux, Agnes; Thierry, Antoine; Essig, Marie; Halimi, Jean-Michel; Munteanu, Eliza; Alain, Sophie; Buchler, Matthias

Cytomegalovirus (CMV) infection occurs frequently after solid organ transplantation. Therapeutic strategies, in particular when to start a curative treatment, has not yet been defined. The purpose of this study was to assess predictive factors associated with spontaneous clearance of CMV DNAemia in kidney transplant recipients. All kidney recipients of a single center were recruited. Patients with at least one positive CMV DNAemia during the first year post transplantation were included in our analysis. Whole blood CMV PCR was performed using Abbott ® RealTime CMV, calibrated according to WHO standards and expressed in log10 IU/ml (Detection = 1.79 IU log10/ml). Post transplantation, prophylaxis (valganciclovir) was given for 3 months for CMV positive recipients (R+) and 6 months for CMV positive donors giving to seronegative recipients (D + R-). Clinical and biological symptoms attributable to CMV were collected. We defined as spontaneous CMV clearance undetectable DNAemia before the fourth follow up without treatment. Results were expressed as mean ± SD. Results were prospectively assessed in a French multicenter validation cohort. Between 05/2012 and 05/2015, 95 patients had at least one positive CMV DNAemia. Thirty-six (37.8%) had spontaneous undetectable DNAemia. Fifty-nine patients had non-spontaneous CMV clearance. ROC analysis showed that an initial CMV DNAemia <2.75 log10/IU/mL was optimal to predict CMV spontaneous clearance. On multivariate analysis, factors associated with spontaneous CMV clearance were initial PCR level lower than 2.75 log10/IU/ml (OR = 33.8, 95% CI [7.1-160.0]), and absence of CMV DNAemia increase of more than 1 log10 between two analyses (OR = 128.0, 95% CI [11.9-1368.0]). Clinical and biological abnormalities were not associated CMV DNAemia spontaneous clearance. Observations made for the principal cohort were validated in an independent cohort of 49 kidney transplanted patients. Initial standardized

Seal Investigations of an Active Clearance Control System Concept

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Taylor, Shawn; Oswald, Jay; DeCastro, Jonathan A.

2006-01-01

In an effort to improve upon current thermal active clearance control methods, a first generation, fast-acting mechanically actuated, active clearance control system has been designed and installed into a non-rotating test rig. In order to harvest the benefit of tighter blade tip clearances, low-leakage seals are required for the actuated carrier segments of the seal shroud to prevent excessive leakage of compressor discharge (P3) cooling air. The test rig was designed and fabricated to facilitate the evaluation of these types of seals, identify seal leakage sources, and test other active clearance control system concepts. The objective of this paper is to present both experimental and analytical investigations into the nature of the face-seal to seal-carrier interface. Finite element analyses were used to examine face seal contact pressures and edge-loading under multiple loading conditions, varied E-seal positions and two new face seal heights. The analyses indicated that moving the E-seal inward radially and reducing face seal height would lead to more uniform contact conditions between the face seal and the carriers. Lab testing confirmed that moving the balance diameter inward radially caused a decrease in overall system leakage.

2A4 binds soluble and insoluble light chain aggregates from AL amyloidosis patients and promotes clearance of amyloid deposits by phagocytosis †.

PubMed

Renz, Mark; Torres, Ronald; Dolan, Philip J; Tam, Stephen J; Tapia, Jose R; Li, Lauri; Salmans, Joshua R; Barbour, Robin M; Shughrue, Paul J; Nijjar, Tarlochan; Schenk, Dale; Kinney, Gene G; Zago, Wagner

2016-09-01

Amyloid light chain (AL) amyloidosis is characterized by misfolded light chain (LC) (amyloid) deposition in various peripheral organs, leading to progressive dysfunction and death. There are no regulatory agency-approved treatments for AL amyloidosis, and none of the available standard of care approaches directly targets the LC protein that constitutes the amyloid. NEOD001, currently in late-stage clinical trials, is a conformation-specific, anti-LC antibody designed to specifically target misfolded LC aggregates and promote phagocytic clearance of AL amyloid deposits. The present study demonstrated that the monoclonal antibody 2A4, the murine form of NEOD001, binds to patient-derived soluble and insoluble LC aggregates and induces phagocytic clearance of AL amyloid in vitro. 2A4 specifically labeled all 21 fresh-frozen organ samples studied, which were derived from 10 patients representing both κ and λ LC amyloidosis subtypes. 2A4 immunoreactivity largely overlapped with thioflavin T-positive labeling, and 2A4 bound both soluble and insoluble LC aggregates extracted from patient tissue. Finally, 2A4 induced macrophage engagement and phagocytic clearance of AL amyloid deposits in vitro. These findings provide further evidence that 2A4/NEOD001 can effectively clear and remove human AL-amyloid from tissue and further support the rationale for the evaluation of NEOD001 in patients with AL amyloidosis.

2A4 binds soluble and insoluble light chain aggregates from AL amyloidosis patients and promotes clearance of amyloid deposits by phagocytosis †

PubMed Central

Renz, Mark; Torres, Ronald; Dolan, Philip J.; Tam, Stephen J.; Tapia, Jose R.; Li, Lauri; Salmans, Joshua R.; Barbour, Robin M.; Shughrue, Paul J.; Nijjar, Tarlochan; Schenk, Dale; Kinney, Gene G.; Zago, Wagner

2016-01-01

Abstract Amyloid light chain (AL) amyloidosis is characterized by misfolded light chain (LC) (amyloid) deposition in various peripheral organs, leading to progressive dysfunction and death. There are no regulatory agency–approved treatments for AL amyloidosis, and none of the available standard of care approaches directly targets the LC protein that constitutes the amyloid. NEOD001, currently in late-stage clinical trials, is a conformation-specific, anti-LC antibody designed to specifically target misfolded LC aggregates and promote phagocytic clearance of AL amyloid deposits. The present study demonstrated that the monoclonal antibody 2A4, the murine form of NEOD001, binds to patient-derived soluble and insoluble LC aggregates and induces phagocytic clearance of AL amyloid in vitro. 2A4 specifically labeled all 21 fresh-frozen organ samples studied, which were derived from 10 patients representing both κ and λ LC amyloidosis subtypes. 2A4 immunoreactivity largely overlapped with thioflavin T–positive labeling, and 2A4 bound both soluble and insoluble LC aggregates extracted from patient tissue. Finally, 2A4 induced macrophage engagement and phagocytic clearance of AL amyloid deposits in vitro. These findings provide further evidence that 2A4/NEOD001 can effectively clear and remove human AL-amyloid from tissue and further support the rationale for the evaluation of NEOD001 in patients with AL amyloidosis. PMID:27494229

14 CFR 25.925 - Propeller clearance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... attitude, whichever is most critical. In addition, there must be positive clearance between the propeller and the ground when in the level takeoff attitude with the critical tire(s) completely deflated and...

30 CFR 56.11005 - Fixed ladder anchorage and toe clearance.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Fixed ladder anchorage and toe clearance. 56.11005 Section 56.11005 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Travelways § 56.11005 Fixed ladder anchorage and toe clearance. Fixed ladders shall be anchored securely and...

30 CFR 56.11005 - Fixed ladder anchorage and toe clearance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Fixed ladder anchorage and toe clearance. 56.11005 Section 56.11005 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Travelways § 56.11005 Fixed ladder anchorage and toe clearance. Fixed ladders shall be anchored securely and...

30 CFR 56.11005 - Fixed ladder anchorage and toe clearance.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Fixed ladder anchorage and toe clearance. 56.11005 Section 56.11005 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Travelways § 56.11005 Fixed ladder anchorage and toe clearance. Fixed ladders shall be anchored securely and...

30 CFR 56.11005 - Fixed ladder anchorage and toe clearance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Fixed ladder anchorage and toe clearance. 56.11005 Section 56.11005 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Travelways § 56.11005 Fixed ladder anchorage and toe clearance. Fixed ladders shall be anchored securely and...

30 CFR 56.11005 - Fixed ladder anchorage and toe clearance.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Fixed ladder anchorage and toe clearance. 56.11005 Section 56.11005 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Travelways § 56.11005 Fixed ladder anchorage and toe clearance. Fixed ladders shall be anchored securely and...

Hemodialysis clearance of glyphosate following a life-threatening ingestion of glyphosate-surfactant herbicide.

PubMed

Garlich, F M; Goldman, M; Pepe, J; Nelson, L S; Allan, M J; Goldstein, D A; Goldfarb, D S; Hoffman, R S

2014-01-01

Ingestion of glyphosate-surfactant herbicides (GlySH) can result in acute kidney injury, electrolyte abnormalities, acidosis, cardiovascular collapse, and death. In severe toxicity, the use of hemodialysis is reported, but largely unsupported by kinetic analysis. We report the dialysis clearance of glyphosate following a suicidal ingestion of a glyphosate-containing herbicide. A 62-year-old man was brought to the emergency department (ED) 8.5 h after drinking a bottle of commercial herbicide containing a 41% solution of glyphosate isopropylamine, in polyoxyethyleneamine (POEA) surfactant and water. He was bradycardic and obtunded with respiratory depression necessitating intubation and mechanical ventilation. Initial laboratory results were significant for the following: pH, 7.11; PCO2, 64 mmHg; PO2, 48 mmHg; potassium, 7.8 mEq/L; Cr 3.3, mg/dL; bicarbonate, 22 mEq/L; anion gap, 18 mEq/L; and lactate, 7.5 mmol/L. Acidosis and hyperkalemia persisted despite ventilation and fluid resuscitation. The patient underwent hemodialysis 16 h post ingestion, after which he demonstrated resolution of acidosis and hyperkalemia, and improvement in clinical status. Serum glyphosate concentrations were drawn prior to, during, and after hemodialysis. The extraction ratio and hemodialysis clearance were calculated to be 91.8% and 97.5 mL/min, respectively. We demonstrate the successful clearance of glyphosate using hemodialysis, with corresponding clinical improvement in a patient with several poor prognostic factors (advanced age, large volume ingested, and impaired consciousness). The effects of hemodialysis on the surfactant compound are unknown. Hemodialysis can be considered when severe acidosis and acute kidney injury complicate ingestion of glyphosate-containing products.

Hepatic macrophage complement receptor clearance function following injury.

PubMed

Cuddy, B G; Loegering, D J; Blumenstock, F A; Shah, D M

1986-03-01

Previous work has demonstrated that in vivo hepatic macrophage complement receptor clearance function is depressed following thermal injury. The present study was carried out to determine if complement receptor function depression is associated with other states of depressed host defense. Hepatic complement receptor clearance function was determined from the hepatic uptake of rat erythrocytes coated with antierythrocyte IgM (EIgM) in rats. Receptor function was determined following cannulation of a carotid artery, laparotomy plus enterotomy, hemorrhagic shock, trauma, thermal injury, acute bacteremia, acute endotoxemia, and injection of erythrocyte stroma, gelatinized lipid emulsion, or colloidal carbon. Hepatic uptake of EIgM was depressed following each of these experimental interventions except arterial cannulation. This effect was shown not to be due to a decrease in hepatic blood flow or depletion of complement and was therefore due to a depression in hepatic macrophage complement receptor clearance function. Thus, impairment of hepatic macrophage complement receptor function is associated with several states of depressed host defense.

Experimental Study of Unshrouded Impeller Pump Stage Sensitivity to Tip Clearance

NASA Technical Reports Server (NTRS)

Williams, Robert W.; Zoladz, Thomas; Storey, Anne K.; Skelley, Stephen E.

2002-01-01

This viewgraph presentation provides information on an experiment. Its objective is to experimentally determine unshrouded impeller performance sensitivity to tip clearance. The experiment included: Determining impeller efficiency at scaled operating conditions in water at MSFC's Pump Test Equipment (PTE) Facility; Testing unshrouded impeller at three different tip clearances; Testing each tip clearance configuration at on- and off-design conditions, and collecting unsteady- and steady-state data in each configuration; Determining impeller efficiency directly using drive line torquemeter and pump inlet and exit total pressure measurements.

Simple geometric algorithms to aid in clearance management for robotic mechanisms

NASA Technical Reports Server (NTRS)

Copeland, E. L.; Ray, L. D.; Peticolas, J. D.

1981-01-01

Global geometric shapes such as lines, planes, circles, spheres, cylinders, and the associated computational algorithms which provide relatively inexpensive estimates of minimum spatial clearance for safe operations were selected. The Space Shuttle, remote manipulator system, and the Power Extension Package are used as an example. Robotic mechanisms operate in quarters limited by external structures and the problem of clearance is often of considerable interest. Safe clearance management is simple and suited to real time calculation, whereas contact prediction requires more precision, sophistication, and computational overhead.

14 CFR 103.23 - Flight visibility and cloud clearance requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Flight visibility and cloud clearance... Flight visibility and cloud clearance requirements. No person may operate an ultralight vehicle when the flight visibility or distance from clouds is less than that in the table found below. All operations in...

14 CFR 103.23 - Flight visibility and cloud clearance requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Flight visibility and cloud clearance... Flight visibility and cloud clearance requirements. No person may operate an ultralight vehicle when the flight visibility or distance from clouds is less than that in the table found below. All operations in...

14 CFR 103.23 - Flight visibility and cloud clearance requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Flight visibility and cloud clearance... Flight visibility and cloud clearance requirements. No person may operate an ultralight vehicle when the flight visibility or distance from clouds is less than that in the table found below. All operations in...

14 CFR 103.23 - Flight visibility and cloud clearance requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Flight visibility and cloud clearance... Flight visibility and cloud clearance requirements. No person may operate an ultralight vehicle when the flight visibility or distance from clouds is less than that in the table found below. All operations in...

14 CFR 103.23 - Flight visibility and cloud clearance requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Flight visibility and cloud clearance... Flight visibility and cloud clearance requirements. No person may operate an ultralight vehicle when the flight visibility or distance from clouds is less than that in the table found below. All operations in...

A conceptual framework for dynamic extension of the red clearance interval as a countermeasure for red-light-running.

PubMed

Gates, Timothy J; Noyce, David A

2016-11-01

This manuscript describes the development and evaluation of a conceptual framework for real-time operation of dynamic on-demand extension of the red clearance interval as a countermeasure for red-light-running. The framework includes a decision process for determining, based on the real-time status of vehicles arriving at the intersection, when extension of the red clearance interval should occur and the duration of each extension. A zonal classification scheme was devised to assess whether an approaching vehicle requires additional time to safely clear the intersection based on the remaining phase time, type of vehicle, current speed, and current distance from the intersection. Expected performance of the conceptual framework was evaluated through modeling of replicated field operations using vehicular event data collected as part of this research. The results showed highly accurate classification of red-light-running vehicles needing additional clearance time and relatively few false extension calls from stopping vehicles, thereby minimizing the expected impacts to signal and traffic operations. Based on the recommended parameters, extension calls were predicted to occur once every 26.5cycles. Assuming a 90scycle, 1.5 extensions per hour were expected per approach, with an estimated extension time of 2.30s/h. Although field implementation was not performed, it is anticipated that long-term reductions in targeted red-light-running conflicts and crashes will likely occur if red clearance interval extension systems are implemented at locations where start-up delay on the conflicting approach is generally minimal, such as intersections with lag left-turn phasing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Kinematics Simulation Analysis of Packaging Robot with Joint Clearance

NASA Astrophysics Data System (ADS)

Zhang, Y. W.; Meng, W. J.; Wang, L. Q.; Cui, G. H.

2018-03-01

Considering the influence of joint clearance on the motion error, repeated positioning accuracy and overall position of the machine, this paper presents simulation analysis of a packaging robot — 2 degrees of freedom(DOF) planar parallel robot based on the characteristics of high precision and fast speed of packaging equipment. The motion constraint equation of the mechanism is established, and the analysis and simulation of the motion error are carried out in the case of turning the revolute clearance. The simulation results show that the size of the joint clearance will affect the movement accuracy and packaging efficiency of the packaging robot. The analysis provides a reference point of view for the packaging equipment design and selection criteria and has a great significance on the packaging industry automation.

Development of (99m)Tc-labeled asymmetric urea derivatives that target prostate-specific membrane antigen for single-photon emission computed tomography imaging.

PubMed

Kimura, Hiroyuki; Sampei, Sotaro; Matsuoka, Daiko; Harada, Naoya; Watanabe, Hiroyuki; Arimitsu, Kenji; Ono, Masahiro; Saji, Hideo

2016-05-15

Prostate-specific membrane antigen (PSMA) is expressed strongly in prostate cancers and is, therefore, an attractive diagnostic and radioimmunotherapeutic target. In contrast to previous reports of PMSA-targeting (99m)Tc-tricarbonyl complexes that are cationic or lack a charge, no anionic (99m)Tc-tricarbonyl complexes have been reported. Notably, the hydrophilicity conferred by both cationic and anionic charges leads to rapid hepatobiliary clearance, whereas an anionic charge might better enhance renal clearance relative to a cationic charge. Therefore, an improvement in rapid clearance would be expected with either cationic or anionic charges, particularly anionic charges. In this study, we designed and synthesized a novel anionic (99m)Tc-tricarbonyl complex ([(99m)Tc]TMCE) and evaluated its use as a single-photon emission computed tomography (SPECT) imaging probe for PSMA detection. Direct synthesis of [(99m)Tc]TMCE from dimethyl iminodiacetate, which contains both the asymmetric urea and succinimidyl moiety important for PSMA binding, was performed using our microwave-assisted one-pot procedure. The chelate formation was successfully achieved even though the precursor included a complicated bioactive moiety. The radiochemical yield of [(99m)Tc]TMCE was 12-17%, with a radiochemical purity greater than 98% after HPLC purification. [(99m)Tc]TMCE showed high affinity in vitro, with high accumulation in LNCaP tumors and low hepatic retention in biodistribution and SPECT/CT studies. These findings warrant further evaluation of [(99m)Tc]TMCE as an imaging agent and support the benefit of this strategy for the design of other PSMA imaging probes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Plasma Creatinine Clearance in the Dog

ERIC Educational Resources Information Center

Frazier, Loy W.

1977-01-01

Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

Active clearance control system for a turbomachine

NASA Technical Reports Server (NTRS)

Johnston, R. P.; Knapp, M. H.; Coulson, C. E. (Inventor)

1982-01-01

An axial compressor is provided with a cooling air manifold surrounding a portion of the shroud, and means for bleeding air from the compressor to the manifold for selectively flowing it in a modulating manner axially along the outer side of the stator/shroud to cool and shrink it during steady state operating conditions so as to obtain minimum shroud/rotor clearance conditions. Provision is also made to selectively divert the flow of cooling air from the manifold during transient periods of operation so as to alter the thermal growth or shrink rate of the stator/shroud and result in adequate clearance with the compressor rotor.

Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients.

PubMed

Rolle, A; Paredes, S; Cortínez, L I; Anderson, B J; Quezada, N; Solari, S; Allende, F; Torres, J; Cabrera, D; Contreras, V; Carmona, J; Ramírez, C; Oliveros, A M; Ibacache, M

2018-05-01

Obesity has been associated with reduced dexmedetomidine clearance, suggesting impaired hepatic function or reduced hepatic blood flow. The aim of this study was to clarify the effect of obesity in dexmedetomidine metabolic clearance. Forty patients, ASA I-III, 18-60 yr old, weighing 47-126 kg, scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body weight measured by dual X-ray absorptiometry. Serial venous samples were drawn during and after dexmedetomidine infusion. A pharmacokinetic analysis was undertaken using non-linear mixed-effect models. In the modelling approach, the total body weight, lean body weight, and adjusted body weight were first tested as size descriptors for volumes and clearances. Hepatic blood flow, liver histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10 and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A decrease in NONMEM objective function value (ΔOFV) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. A total of 637 dexmedetomidine serum samples were obtained. A two-compartmental model scaled to measured lean weight adequately described the dexmedetomidine pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance (ΔOFV=-5.878). Other factors, including fat mass, histopathological damage, and differential expression of enzymes, did not affect the dexmedetomidine clearance in the population studied (ΔOFV<3.84). We did not find a negative influence of obesity in dexmedetomidine clearance when doses were adjusted to lean body weight. Liver blood flow showed a significant effect on dexmedetomidine clearance. NCT02557867. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

No association between endogenous retinoic acid and human papillomavirus clearance or incident cervical lesions in Brazilian women

PubMed Central

Siegel, Erin M.; Salemi, Jason L.; Craft, Neal E.; Villa, Luisa L.; Ferenczy, Alex; Franco, Eduardo L.; Giuliano, Anna R.

2010-01-01

Background Although oncogenic human papillomavirus (HPV) infections have been established as the necessary cause of cervical cancer, most HPV infections are transient and rarely progress to squamous cervical lesions. The activity of HPV is tightly associated with epithelial cell differentiation; therefore regulators of differentiation, such as retinoic acid, have been considered targets for the prevention of HPV-associated squamous intraepithelial lesion (SIL) development. Purpose The purpose of this study was to determine the association between circulating retinoic acid (RA) and early events in cervical carcinogenesis, specifically type-specific HPV clearance and SIL detection. Methods Archived blood samples from 643 women participating in the Ludwig-McGill Cohort in São Paulo, Brazil were analyzed by high-pressure liquid chromatography for three RA isomers (all-trans, 13-cis, and 9-cis RA). A type-specific HPV clearance event was defined as two consecutive visits negative for that HPV type during follow-up for the 364 HPV positive women. Among the 643 women in this analysis, 78 were diagnosed with incident SIL. Results The probability of clearing an oncogenic HPV infection was not significantly different across RA isomer quartiles. There was a suggestion that increasing all-trans RA increased rate of non-oncogenic HPV clearance (p-trend=0.05). There was no association observed between serum RA levels and incident SIL. Conclusions Our results suggest that elevated circulating RA isomer levels do not increase rates of HPV clearance or reduce risk of incident SIL. The role of RA in the inhibition of HPV induced carcinogenesis, as demonstrated in vitro, lacks confirmatory evidence within epidemiologic studies among women. PMID:20606041

Supine lung clearance of Tc-99m DTPA and HMPAO aerosols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chia-Hung Kao; Hui-Tzu Lin; Shu-Ling Yu

1995-07-01

The speed of Tc-99m DTPA/HMPAO radioaerosol clearance from the lungs that is represented as a slope from lungs to blood was measured in 23 male normal controls using commercial lung radioaerosol delivery units in the supine position in order to avoid the influences of gravity. The right lung was selected and three regions of interest were created for equal subdivisions of the upper, middle, and lower third. The results show that the clearance of Tc-99m DTPA/HMPAO aerosols in the upper lung is lowest. The difference between upper and lower lungs for Tc-99m DTPA/HMPAO aerosol clearances are significant. The clearance ofmore » Tc-99m DTPA aerosols was significantly faster than those of Tc-99m HMPAO in any region. The authors conclude that, although the effect of gravity disappears in the supine position in our study, the differences of aerosol clearance in different regions are still significant. Lipophilic Tc-99m HMPAO aerosols were slower than those of hydrophilic Tc-99m DTPA, which suggests there are at least two different mechanisms. 22 refs., 2 figs., 1 tab.« less

Impairment of nasal mucociliary clearance in woodworkers in the furniture industry

PubMed Central

Black, A.; Evans, J. C.; Hadfield, Esme H.; Macbeth, R. G.; Morgan, A.; Walsh, M.

1974-01-01

Black, A., Evans, J. C., Hadfield, Esme H., Macbeth, R. G., Morgan, A., and Walsh, M. (1974).British Journal of Industrial Medicine,31, 10-17. Impairment of nasal mucociliary clearance in woodworkers in the furniture industry. Measurements of mucociliary clearance from the anterior end of the middle turbinate were made using technetium-99m-labelled particles in nine woodworkers from the furniture industry and in 12 controls, none of whom had been occupationally exposed to wood dust. Clearance rates in the controls ranged from 1·9 to 18·5 mm min-1 with a mean of 6·8. These values are in good agreement with measurements reported elsewhere for normal subjects. Only one of the woodworkers had a clearance rate which fell within the normal range and he had been occupationally exposed for the shortest period (6 years). In four woodworkers clearance was very slow (< 1 mm min-1) and in three there was almost complete stasis. The results of this preliminary investigation suggest that nasal mucociliary function is significantly impaired in workers who have been exposed to wood dust in the furniture industry for more than 10 years. PMID:4821406

Lung clearance index is a repeatable and sensitive indicator of radiological changes in bronchiectasis.

PubMed

Rowan, Stephen A; Bradley, Judy M; Bradbury, Ian; Lawson, John; Lynch, Tom; Gustafsson, Per; Horsley, Alex; O'Neill, Katherine; Ennis, Madeleine; Elborn, J Stuart

2014-03-01

In bronchiectasis there is a need for improved markers of lung function to determine disease severity and response to therapy. To assess whether the lung clearance index is a repeatable and more sensitive indicator of computed tomography (CT) scan abnormalities than spirometry in bronchiectasis. Thirty patients with stable bronchiectasis were recruited and lung clearance index, spirometry, and health-related quality of life measures were assessed on two occasions, 2 weeks apart when stable (study 1). A separate group of 60 patients with stable bronchiectasis was studied on a single visit with the same measurements and a CT scan (study 2). In study 1, the intervisit intraclass correlation coefficient for the lung clearance index was 0.94 (95% confidence interval, 0.89 to 0.97; P < 0.001). In study 2, the mean age was 62 (10) years, FEV1 76.5% predicted (18.9), lung clearance index 9.1 (2.0), and total CT score 14.1 (10.2)%. The lung clearance index was abnormal in 53 of 60 patients (88%) and FEV1 was abnormal in 37 of 60 patients (62%). FEV1 negatively correlated with the lung clearance index (r = -0.51, P < 0.0001). Across CT scores, there was a relationship with the lung clearance index, with little evidence of an effect of FEV1. There were no significant associations between the lung clearance index or FEV1 and health-related quality of life. The lung clearance index is repeatable and a more sensitive measure than FEV1 in the detection of abnormalities demonstrated on CT scan. The lung clearance index has the potential to be a useful clinical and research tool in patients with bronchiectasis.

Novel sensors to enable closed-loop active clearance control in gas turbine engines

NASA Astrophysics Data System (ADS)

Geisheimer, Jonathan; Holst, Tom

2014-06-01

Active clearance control within the turbine section of gas turbine engines presents and opportunity within aerospace and industrial applications to improve operating efficiencies and the life of downstream components. Open loop clearance control is currently employed during the development of all new large core aerospace engines; however, the ability to measure the gap between the blades and the case and close down the clearance further presents as opportunity to gain even greater efficiencies. The turbine area is one of the harshest environments for long term placement of a sensor in addition to the extreme accuracy requirements required to enable closed loop clearance control. This paper gives an overview of the challenges of clearance measurements within the turbine as well as discusses the latest developments of a microwave sensor designed for this application.

Does sleep disturbance affect the amyloid clearance mechanisms in Alzheimer's disease?

PubMed

Yulug, Burak; Hanoglu, Lutfu; Kilic, Ertugrul

2017-10-01

Sleep is an important factor that plays a key role in Alzheimer's disease pathogenesis. However, it is still unclear whether poor-quality sleep may overlap with sleep disturbances in the underlying dysfunctional mechanisms of amyloid beta (Aβ) clearance metabolism. Here, we aimed to evaluate the current evidence on the role of sleep deprivation in Aβ clearance metabolism. To that end, we discuss possible mechanisms underlying the bidirectional interaction between the sleep deprivation and Aβ clearance pathways. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

Reduced effectiveness of escitalopram in the forced swimming test is associated with increased serotonin clearance rate in food restricted rats

PubMed Central

France, CP; Li, J-X; Owens, WA; Koek, W; Toney, GM; Daws, LC

2012-01-01

Efficacy of antidepressant drugs is often limited. One of the limiting factors may be diet. This study shows that the effect of escitalopram in the forced swimming test is diminished in rats by food restriction that decreased body weight by 8%. The primary target for escitalopram is the serotonin (5-HT) transporter. Using high-speed chronoamperometry to measure 5-HT clearance in vivo in rats fed the same food restricted diet, the rate of 5-HT clearance from extracellular fluid in brain was dramatically increased. Increased 5-HT transporter function under conditions of dietary restriction might contribute to the decreased effect of escitalopram. These results suggest that diet plays an integral role in determining efficacy of antidepressant drugs, and might well generalize to other psychoactive drugs that impinge upon the 5-HT transporter. PMID:19419596

76 FR 59379 - Proposed Information Collection; Comment Request; Generic Clearance for Research in Development...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

...-XXXX. Type of Review: Generic Clearance Request. Title: Generic Clearance for Research in Development..., filing of petitions and applications and agency #0;statements of organization and functions are examples... Proposed Information Collection; Comment Request; Generic Clearance for Research in Development of...

Clearance of Vancomycin-Resistant Enterococcus Concomitant With Administration of a Microbiota-Based Drug Targeted at Recurrent Clostridium difficile Infection.

PubMed

Dubberke, Erik R; Mullane, Kathleen M; Gerding, Dale N; Lee, Christine H; Louie, Thomas J; Guthertz, Harriet; Jones, Courtney

2016-09-01

Background.  Vancomycin-resistant Enterococcus (VRE) is a major healthcare-associated pathogen and a well known complication among transplant and immunocompromised patients. We report on stool VRE clearance in a post hoc analysis of the Phase 2 PUNCH CD study assessing a microbiota-based drug for recurrent Clostridium difficile infection (CDI). Methods.  A total of 34 patients enrolled in the PUNCH CD study received 1 or 2 doses of RBX2660 (microbiota suspension). Patients were requested to voluntarily submit stool samples at baseline and at 7, 30, and 60 days and 6 months after the last administration of RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6 µg/mL vancomycin and Gram staining. Vancomycin resistance was confirmed by Etest. Results.  VRE status (at least 1 test result) was available for 30 patients. All stool samples for 19 patients (63.3%, mean age 61.7 years, 68% female) tested VRE negative. Eleven patients (36.7%, mean age 75.5 years, 64% female) were VRE positive at the first test (baseline or 7-day follow-up). Of these patients, 72.7%, n = 8 converted to negative as of the last available follow-up (30 or 60 days or 6 months). Of the other 3: 1 died (follow-up data not available); 1 patient remained positive at all follow-ups; 1 patient retested positive at 6 months with negative tests during the interim. Conclusions.  Although based on a small sample size, this secondary analysis demonstrated the possibility of successfully converting a high percentage of VRE-positive patients to negative in a recurrent CDI population with RBX2660.

Impact of food on hepatic clearance of patients after endoscopic sphincterotomy.

PubMed

Chan, Hoi-Hung; Lai, Kwok-Hung; Lin, Chiun-Ku; Tsai, Wei-Lun; Peng, Nan-Jing; Hsu, Ping-I; Lo, Gin-Ho; Wei, Min-Ching; Wang, E-Ming; Chang, Hsueh-Wen

2009-01-01

The recurrence rate of common bile duct stones (CBDS) is around 3-21% after treatment by endoscopic sphincterotomy (ES). Fatty meal has been shown to improve hepatic clearance in both patients with intact gallbladder and post-cholecystectomy after ES. This study tested the effects of different kinds of food on hepatic clearance by using quantitative cholescintigraphy (QC) in patients after ES. Forty-seven patients after ES with abnormal QC were enrolled in our study. Complete ablation of sphincter function was confirmed by sphincter of Oddi manometry. Fasting QC was done in every patient shortly after normalization of liver function, and then followed with low-fat and fatty-meal QC. Each of the 47 subjects was observed for the effect on hepatic clearance at 3 different levels of treatments (diets and fasting). Additionally, possible factors responsible for recurrent CBDS were investigated by means of logistic regression. Both fatty and low-fat meals could significantly improve hepatic clearance compared with fasting in most patients after ES. But the response to food types was individualized. All patients tolerated the meals well. There was no significant relationship between the recurrence of CBDS and sex, age, intact gallbladder and presence of juxtapapillary diverticulum, CBD size, and improvement in hepatic clearance (> or = 5%) by food. Both fatty and low-fat meals improved hepatic clearance in most of the patients with CBDS after ES, but the response to meals was individualized. Therefore, there is no need to restrict the amount of fat intake for patients who have undergone ES.

Prognostic significance of blood lactate and lactate clearance in trauma patients.

PubMed

Régnier, Marie-Alix; Raux, Mathieu; Le Manach, Yannick; Asencio, Yves; Gaillard, Johann; Devilliers, Catherine; Langeron, Olivier; Riou, Bruno

2012-12-01

Lactate has been shown to be a prognostic biomarker in trauma. Although lactate clearance has already been proposed as an intermediate endpoint in randomized trials, its precise role in trauma patients remains to be determined. Blood lactate levels and lactate clearance (LC) were calculated at admission and 2 and 4 h later in trauma patients. The association of initial blood lactate level and lactate clearance with mortality was tested using receiver-operating characteristics curve, logistic regression using triage scores, Trauma Related Injury Severity Score as a reference standard, and reclassification method. The authors evaluated 586 trauma patients (mean age 38±16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate levels at admission were elevated in 327 (56%) patients. The lactate clearance should be calculated within the first 2 h after admission as LC0-2 h was correlated with LC0-4 h (R=0.55, P<0.001) but not with LC2-4 h (R=0.04, not significant). The lactate clearance provides additional predictive information to initial blood lactate levels and triage scores and the reference score. This additional information may be summarized using a categorical approach (i.e., less than or equal to -20 %/h) in contrast to initial blood lactate. The results were comparable in patients with high (5 mM/l or more) initial blood lactate. Early (0-2 h) lactate clearance is an important and independent prognostic variable that should probably be incorporated in future decision schemes for the resuscitation of trauma patients.

Gas turbine engine active clearance control

NASA Technical Reports Server (NTRS)

Deveau, Paul J. (Inventor); Greenberg, Paul B. (Inventor); Paolillo, Roger E. (Inventor)

1985-01-01

Method for controlling the clearance between rotating and stationary components of a gas turbine engine are disclosed. Techniques for achieving close correspondence between the radial position of rotor blade tips and the circumscribing outer air seals are disclosed. In one embodiment turbine case temperature modifying air is provided in flow rate, pressure and temperature varied as a function of engine operating condition. The modifying air is scheduled from a modulating and mixing valve supplied with dual source compressor air. One source supplies relatively low pressure, low temperature air and the other source supplies relatively high pressure, high temperature air. After the air has been used for the active clearance control (cooling the high pressure turbine case) it is then used for cooling the structure that supports the outer air seal and other high pressure turbine component parts.

Foot clearance and variability in mono- and multifocal intraocular lens users during stair navigation.

PubMed

Renz, Erik; Hackney, Madeleine; Hall, Courtney

2016-01-01

Intraocular lenses (IOLs) provide distance and near refraction and are becoming the standard for cataract surgery. Multifocal glasses increase variability of toe clearance in older adults navigating stairs and increase fall risk; however, little is known about the biomechanics of stair navigation in individuals with multifocal IOLs. This study compared clearance while ascending and descending stairs in individuals with monofocal versus multifocal IOLs. Eight participants with multifocal IOLs (4 men, 4 women; mean age = 66.5 yr, standard deviation [SD] = 6.26) and fifteen male participants with monofocal IOLs (mean age = 69.9 yr, SD = 6.9) underwent vision and mobility testing. Motion analysis recorded kinematic and custom software-calculated clearances in three-dimensional space. No significant differences were found between groups on minimum clearance or variability. Clearance differed for ascending versus descending stairs: the first step onto the stair had the greatest toe clearance during ascent, whereas the final step to the floor had the greatest heel clearance during descent. This preliminary study indicates that multifocal IOLs have similar biomechanic characteristics to monofocal IOLs. Given that step characteristics are related to fall risk, we can tentatively speculate that multifocal IOLs may carry no additional fall risk.

Clearance of Apoptotic Photoreceptors

PubMed Central

Hisatomi, Toshio; Sakamoto, Taiji; Sonoda, Koh-hei; Tsutsumi, Chikako; Qiao, Hong; Enaida, Hiroshi; Yamanaka, Ichiro; Kubota, Toshiaki; Ishibashi, Tatsuro; Kura, Shinobu; Susin, Santos A.; Kroemer, Guido

2003-01-01

The effective phagocytotic clearance of apoptotic debris is fundamental to the maintenance of neural tissues during apoptosis. Retinal photoreceptors undergo apoptosis after retinal detachment. Although their induction phase of apoptosis has been well discussed, their phagocytotic process remains quite unclear. We herein demonstrate that apoptotic photoreceptors are selectively eliminated from their physiological localization, the outer nuclear layer, to the subretinal space, and then phagocytosed by monocyte-derived macrophages. This could be shown by an ultrastructural and immunophenotypic analysis. Moreover, in chimera mice expressing transgenic green fluorescent protein in bone marrow-derived cells, the local infiltration of macrophages could be detected after retinal detachment-induced photoreceptor apoptosis. The local injection of an antibody blocking the phosphatidylserine receptor (PSR) or a peptide (GRGDSP)-blocking integrin αvβ3 revealed that phagocytotic clearance involves the PSR as well as integrin αvβ3 in vivo. Importantly, the level of blockade obtained with these reagents was different. Although anti-PSR increased the frequency of apoptotic cells that fail to bind to macrophages, GRGDSP prevented the engulfment (but not the recognition) of apoptotic photoreceptor cells by macrophages. To our knowledge, this is the first report describing the mechanisms through which apoptotic photoreceptors are selectively eliminated via a directional process in the subretinal space. PMID:12759244

Evaluation of lung clearance of inhaled pertechnegas.

PubMed

Fanti, S; Compagnone, G; Pancaldi, D; Franchi, R; Corbelli, C; Marengo, M; Onofri, C; Galassi, R; Levorato, M; Monetti, N

1996-02-01

Pertechnegas is a new ventilation agent produced by modifying the atmosphere of combustion of Technegas. Due to its rapid disappearance from the lungs, Pertechnegas has been suggested as useful in measuring pulmonary epithelial permeability. This study aimed to assess the reliability of ventilation scans with Pertechnegas to evaluate alveolar-capillary permeability. Six non-smokers with no evidence of pulmonary disease were investigated. Scintigraphic data were used to evaluate the site of Pertechnegas deposition (by assessing the Penetration Index [PI] of the gas), its clearance rate (by calculating the time to half-clearance [T1/2]) and its lung distribution (by means of a pixel-by-pixel analysis. PI measurements produced a mean value of 88.8 +/- 13.3% (range 69-117%). Time activity curves showed a fast clearance in all cases (mean T1/2 = 10.7 +/- 2.1 min, range 8.1-14.3 min). Comparison of statistical indices of uniform deposition (skewness and kurtosis) indicated satisfactory homogeneity of Pertechnegas distribution throughout the lungs. These data show that after inhalation Pertechnegas has a peripheral deposition and a homogeneous distribution in the lungs and is rapidly cleared through the alveolar-capillary barrier. In conclusion Pertechnegas can be recommended as a potential radiopharmaceutical for studying the pulmonary epithelial barrier.

Traffic incident management quick clearance laws : a national review of best practices.

DOT National Transportation Integrated Search

2008-12-01

Constituting Quick Clearance Laws, three types of general legislation Move Over, Driver Removal, and Authority Removal laws - support concurrent Quick Clearance operations intended to enhance motorist and responder safety, as well as reduce...

Clearance Analysis of CTC2 (on ELC4) to S-TRRJ HRS Radiator Rotation Envelope

NASA Technical Reports Server (NTRS)

Liddle, Donn

2014-01-01

) as defined by nine preexisting Space Vision System (SVS) targets affixed to the forward/zenith side of the S1 and S3 truss segments. The location of the outboard edge of the S-TRRJ radiator would also be measured when positioned at the angle of closest approach to CTC2 (gamma = 35.0 degrees). This data would allow the Digital Pre-Assembly Group to predict how the ELC4 would sit on the UCCAS and how that would translate into the clearance between CTC2 and the S-TRRJ radiators. Phase II: After the ELC4 was delivered and installed into the UCCAS, the position of the CTC2 mounting plate on the inboard face of ELC4, would be measured in the ISSACS coordinate system relative to the SVS control points used in Phase I. Although CTC2 would not yet be mounted on ELC4, the working envelope of CTC2 could be mathematically added to the measured position of ELC4 to produce a best estimate for CTC2's mounted location. Comparing CTC2's best estimated location to the S-TRRJ radiator (measured in Phase I); relative to the ISSACS coordinate system, would provide a direct measurement of the expected clearance. Due to the impending delivery of ELC4 (scheduled for January 2011), planning for the Phase I clearance analysis began immediately. Using the Dynamic Onboard Ubiquitous Graphics (DOUG) program, ISAG designed a way to acquire images of the SVS control points on truss segments S1 and S3, the aft facing edge of the S-TRRJ Heat Rejection Subsystem (HRS) radiator, and the three UCCAS latch mechanisms mounted on the zenith face of the S3 truss using the Space Station Remote Manipulator System (SSRMS). To minimize the number of SSRMS movements, the Special Purpose Dexterous Manipulator (SPDM) would be attached to the SSRMS. This would make it possible to park the SPDM in one position and acquire multiple images by changing the viewing orientation of the SPDM body cameras using the pan/tilt units on which they are mounted. Using this implementation concept, ISAG identified four SSRMS

Physiological stability and renal clearance of ultrasmall zwitterionic gold nanoparticles: Ligand length matters

NASA Astrophysics Data System (ADS)

Ning, Xuhui; Peng, Chuanqi; Li, Eric S.; Xu, Jing; Vinluan, Rodrigo D.; Yu, Mengxiao; Zheng, Jie

2017-05-01

Efficient renal clearance has been observed from ultrasmall zwitterionic glutathione-coated gold nanoparticles (GS-AuNPs), which have broad preclinical applications in cancer diagnosis and kidney functional imaging. However, origin of such efficient renal clearance is still not clear. Herein, we conducted head-to-head comparison on physiological stability and renal clearance of two zwitterionic luminescent AuNPs coated with cysteine and glycine-cysteine (Cys-AuNPs and Gly-Cys-AuNPs), respectively. While both of them exhibited similar surface charges and the same core sizes, additional glycine slightly increased the hydrodynamic diameter of the AuNPs by 0.4 nm but significantly enhanced physiological stability of the AuNPs as well as altered their clearance pathways. These studies indicate that the ligand length, in addition to surface charges and size, also plays a key role in the physiological stability and renal clearance of ultrasmall zwitterionic inorganic NPs.

Design optimization of dual-axis driving mechanism for satellite antenna with two planar revolute clearance joints

NASA Astrophysics Data System (ADS)

Bai, Zheng Feng; Zhao, Ji Jun; Chen, Jun; Zhao, Yang

2018-03-01

In the dynamic analysis of satellite antenna dual-axis driving mechanism, it is usually assumed that the joints are ideal or perfect without clearances. However, in reality, clearances in joints are unavoidable due to assemblage, manufacturing errors and wear. When clearance is introduced to the mechanism, it will lead to poor dynamic performances and undesirable vibrations due to impact forces in clearance joint. In this paper, a design optimization method is presented to reduce the undesirable vibrations of satellite antenna considering clearance joints in dual-axis driving mechanism. The contact force model in clearance joint is established using a nonlinear spring-damper model and the friction effect is considered using a modified Coulomb friction model. Firstly, the effects of clearances on dynamic responses of satellite antenna are investigated. Then the optimization method for dynamic design of the dual-axis driving mechanism with clearance is presented. The objective of the optimization is to minimize the maximum absolute vibration peak of antenna acceleration by reducing the impact forces in clearance joint. The main consideration here is to optimize the contact parameters of the joint elements. The contact stiffness coefficient, damping coefficient and the dynamic friction coefficient for clearance joint elements are taken as the optimization variables. A Generalized Reduced Gradient (GRG) algorithm is used to solve this highly nonlinear optimization problem for dual-axis driving mechanism with clearance joints. The results show that the acceleration peaks of satellite antenna and contact forces in clearance joints are reduced obviously after design optimization, which contributes to a better performance of the satellite antenna. Also, the application and limitation of the proposed optimization method are discussed.

Test Rig for Active Turbine Blade Tip Clearance Control Concepts: An Update

NASA Technical Reports Server (NTRS)

Taylor, Shawn; Steinetz, Bruce; Oswald, Jay; DeCastro, Jonathan; Melcher, Kevin

2006-01-01

The objective is to develop and demonstrate a fast-acting active clearance control system to improve turbine engine performance, reduce emissions, and increase service life. System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA's Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

Increased Glyburide Clearance in the Pregnant Mouse Model

PubMed Central

Zhou, Lin; Zhang, Yi; Hebert, Mary F.; Unadkat, Jashvant D.

2010-01-01

Glyburide (GLB) is an oral sulfonylurea, commonly used for the treatment of gestational diabetes mellitus. It has been reported that the clearance of GLB in pregnant women is significantly higher than that in nonpregnant women. The molecular mechanism by which pregnancy increases the clearance of GLB is not known, but it may be caused by increased CYP3A activity. Because liver tissue from pregnant women is not readily available, in the present study, we investigated the mechanism of such pregnancy-related changes in GLB disposition in a mouse model. We demonstrated that the systemic clearance of GLB in pregnant mice was increased approximately 2-fold (p < 0.01) compared with nonpregnant mice, a magnitude of change similar to that observed in the clinical study. Plasma protein binding of GLB in mice was not altered by pregnancy. The half-life of GLB depletion in hepatic S-9 fractions of pregnant mice was significantly shorter than that of nonpregnant mice. Moreover, GLB depletion was markedly inhibited by ketoconazole, a potent inhibitor of mouse Cyp3a, suggesting that GLB metabolism in mice is primarily mediated by hepatic Cyp3a. These data suggest that the increased systemic clearance of GLB in pregnant mice is likely caused by an increase in hepatic Cyp3a activity during pregnancy, and they provide a basis for further mechanistic understanding and analysis of pregnancy-induced alterations in the disposition of GLB and drugs that are predominantly and extensively metabolized by CYP3A/Cyp3a. PMID:20558597

Impaired lipid clearance in patients with previous acute pancreatitis.

PubMed Central

Guzmán, S; Nervi, F; Llanos, O; León, P; Valdivieso, V

1985-01-01

Fasting serum triglycerides were measured in 52 patients who had sustained an attack of pancreatitis (gall stone related 33, alcoholism six) at least six months earlier. Several patients (23%) had raised fasting serum triglycerides, with a type IV phenotype in all but one patient. The 40 patients with normal fasting serum triglycerides received an oral load of 100 g sunflower oil to compare their clearance of dietary triglycerides with that of a control group of 54 subjects. The clearance of ingested triglycerides was significantly impaired in the patients - irrespective of the presumed aetiological factor, or clinical condition associated with pancreatitis - compared with the clearance in controls. A triglyceride tolerance test is the only way to detect those patients in whom a future attack of pancreatitis may be precipitated by a diet rich in fat, or endogenous over production of triglycerides as after an alcoholic debauch. PMID:4029716

Participation of the hypophyseal-adrenal cortex system in thrombin clearance during immobilization stress

NASA Technical Reports Server (NTRS)

Kudryashov, B. A.; Uljanov, A. M.; Shapiro, F. B.; Bazazyan, G. G.

1981-01-01

Thrombin marked with I-131 resulted in a considerable increase of the thrombined clearance rate in healthy male rats during stress caused by an immobilization lasting 30 minutes, and in an increase of thrombin clearance occurred by a combination of immobilization and administration of adrenocorticotropin (ACTH). Contrary to ACTH, the thrombin clearance is not stimulated in healthy animals by hydrocortisone. The results of the examination are presented.

Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

PubMed

Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

2016-05-05

Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

Effects of nitrogen dioxide on respiratory tract clearance in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rasmussen, R.E.; Mannix, R.C.; Oldham, M.J.

1994-01-01

During growth and development, young children are periodically exposed to relatively high concentrations of various air contaminants, including tobacco smoke and environmental pollutants generated by fossil fuel use. The effects of these exposures on respiratory function and lung development are difficult to determine because of interindividual variation and lack of accurate dosimetry. To provide information on the effects of chronic exposure to a common indoor and outdoor pollutant during lung development, a study was performed to assess the effects of exposure to two concentrations of nitrogen dioxide (NO[sub 2]; 0.5 or 10 ppm) on tracer particle clearance from the airwaysmore » of ferrets exposed during postnatal respiratory tract development. Separate groups of ferrets were exposed nose-only to the test atmospheres or clean air 4 h/d, 5 d/wk, for either 8 or 15 wk. Those animals exposed for 8 wk were subsequently housed in a filtered air environment until the particle clearance measurements commenced at 3 wk prior to the end of the 15-wk exposure protocol. Radiolabeled ([sup 51]Cr) tracer particles were deposited in the respiratory tract of all animals by inhalation, and the clearance rates from the head and thoracic regions were separately monitored for 18 d. No significant effects of the NO[sub 2] exposure on head airways clearance were seen. In contrast, the rates of particle clearance from the thorax of both the 8- and 15-wk groups exposed to 10 ppm NO[sub 2] were significantly reduced, and did not differ from each other. Thoracic clearance was also reduced in animals exposed to 0.5 ppm, but the rate was not significantly different from that of the clean air exposed controls. These results show that NO[sub 2] at moderate concentrations caused highly significant changes in the deep lung of the juvenile ferret, and suggest that impairment of the clearance function may be only slowly recovered after chronic exposure. 35 refs., 1 fig., 1 tab.« less

Antibiotics taken for other illnesses and spontaneous clearance of Helicobacter pylori infection in children.

PubMed

Broussard, Cheryl S; Goodman, Karen J; Phillips, Carl V; Smith, Mary Ann; Fischbach, Lori A; Day, R Sue; Aragaki, Corinne C

2009-08-01

Factors that determine persistence of untreated Helicobacter pylori (H. pylori) infection in childhood are not well understood. We estimated risk differences for the effect of incidental antibiotic exposure on the probability of a detected clearance at the next test after an initial detected H. pylori infection. The Pasitos Cohort Study (1998-2005) investigated predictors of H. pylori infection in children from El Paso, Texas, and Juarez, Mexico. Children were screened for infection at 6-month target intervals from 6 to 84 months of age, using the 13C-urea breath test corrected for body-size-dependent variation in CO2 production. Exposure was defined as courses of any systemic antibiotic (systemic) or those with anti-H. pylori action (HP-effective) reported for the interval between initial detected infection and next test. Binomial regression models included country of residence, mother's education, adequacy of prenatal care, age at infection, and interval between tests. Of 205 children with a test result and antibiotic data following a detected infection, the number of children who took > or =1 course in the interval between tests was 74 for systemic and 33 for HP-effective. The proportion testing negative at the next test was 66% for 0 courses, 72% for > or =1 systemic course, and 79% for > or =1 HP-effective course. Adjusted risk differences (95%CI) for apparent clearance, comparing > or =1 to 0 courses were 10% (1-20%) for systemic and 11% (0-21%) for HP-effective. Incidental antibiotic exposure appears to influence the duration of childhood H. pylori infection but seems to explain only a small portion of spontaneous clearance. Copyright 2009 John Wiley & Sons, Ltd.

Wear in ceramic on ceramic type lumbar total disc replacement: effect of radial clearance.

PubMed

Shankar, S; Kesavan, D

2015-01-01

The wear of the bearing surfaces of total disc replacement (TDR) is a key problem leads to reduction in the lifetime of the prosthesis and it mainly occurs due to the range of clearances of the articulating surface between the superior plate and core. The objective of this paper is to estimate the wear using finite element concepts considering the different radial clearances between the articulating surfaces of ceramic on ceramic type Lumbar Total Disc Replacement (LTDR). The finite element (FE) model was subjected to wear testing protocols according to loading profile of International Standards Organization (ISO) 18192 standards through 10 million cycles. The radial clearance value of 0.05 mm showed less volumetric wear when compared with other radial clearance values. Hence, low radial clearance values are suitable for LTDR to minimize the wear.

Cancer nanomedicine: a review of recent success in drug delivery.

PubMed

Tran, Stephanie; DeGiovanni, Peter-Joseph; Piel, Brandon; Rai, Prakash

2017-12-11

Cancer continues to be one of the most difficult global healthcare problems. Although there is a large library of drugs that can be used in cancer treatment, the problem is selectively killing all the cancer cells while reducing collateral toxicity to healthy cells. There are several biological barriers to effective drug delivery in cancer such as renal, hepatic, or immune clearance. Nanoparticles loaded with drugs can be designed to overcome these biological barriers to improve efficacy while reducing morbidity. Nanomedicine has ushered in a new era for drug delivery by improving the therapeutic indices of the active pharmaceutical ingredients engineered within nanoparticles. First generation nanomedicines have received widespread clinical approval over the past two decades, from Doxil ® (liposomal doxorubicin) in 1995 to Onivyde ® (liposomal irinotecan) in 2015. This review highlights the biological barriers to effective drug delivery in cancer, emphasizing the need for nanoparticles for improving therapeutic outcomes. A summary of different nanoparticles used for drug delivery applications in cancer are presented. The review summarizes recent successes in cancer nanomedicine in the clinic. The clinical trials of Onivyde leading to its approval in 2015 by the Food and Drug Adminstration are highlighted as a case study in the recent clinical success of nanomedicine against cancer. Next generation nanomedicines need to be better targeted to specifically destroy cancerous tissue, but face several obstacles in their clinical development, including identification of appropriate biomarkers to target, scale-up of synthesis, and reproducible characterization. These hurdles need to be overcome through multidisciplinary collaborations across academia, pharmaceutical industry, and regulatory agencies in order to achieve the goal of eradicating cancer. This review discusses the current use of clinically approved nanomedicines, the investigation of nanomedicines in clinical

Eradication of acute promyelocytic leukemia-initiating cells by PML/RARA-targeting.

PubMed

Nasr, Rihab; de Thé, Hugues

2010-06-01

Acute promyelocytic leukemia (APL) is characterized by a t(15;17) translocation that yields a PML/RARA fusion protein. Expression of PML/RARA, a potent transcriptional repressor, induces APL in mice. Both retinoic acid (RA) and arsenic trioxide directly target PML/RARA-mediated transcriptional repression and protein stability, inducing rapid differentiation of the promyelocytes and clinical remission in most APL patients. RA also triggers growth arrest and progressive clearance of leukemia initiating cells (LIC), both ex vivo and in vivo. Suboptimal RA concentrations or expression of the PLZF/RARA variant allows complete RA-induced differentiation, but neither LIC clearance nor disease remission. Thus, RA-induced differentiation and LIC clearance may be uncoupled. The RA/arsenic trioxide association, which dramatically synergizes for PML/RARA degradation but not for differentiation, rapidly clears LIC in a proteasome-dependent manner, resulting in APL eradication in murine models and patients. Collectively, these results demonstrate that LIC clearance, which mirrors PML/RARA degradation, is the primary basis for APL cure by the RA/arsenic trioxide association, rather than differentiation. Oncogene degradation could be a generally applicable therapeutic strategy to clear LICs in several types of tumors.

Blood lactate clearance after maximal exercise depends on active recovery intensity.

PubMed

Devlin, J; Paton, B; Poole, L; Sun, W; Ferguson, C; Wilson, J; Kemi, O J

2014-06-01

High-intensity exercise is time-limited by onset of fatigue, marked by accumulation of blood lactate. This is accentuated at maximal, all-out exercise that rapidly accumulates high blood lactate. The optimal active recovery intensity for clearing lactate after such maximal, all-out exercise remains unknown. Thus, we studied the intensity-dependence of lactate clearance during active recovery after maximal exercise. We constructed a standardized maximal, all-out treadmill exercise protocol that predictably lead to voluntary exhaustion and blood lactate concentration>10 mM. Next, subjects ran series of all-out bouts that increased blood lactate concentration to 11.5±0.2 mM, followed by recovery exercises ranging 0% (passive)-100% of the lactate threshold. Repeated measurements showed faster lactate clearance during active versus passive recovery (P<0.01), and that active recovery at 60-100% of lactate threshold was more efficient for lactate clearance than lower intensity recovery (P<0.05). Active recovery at 80% of lactate threshold had the highest rate of and shortest time constant for lactate clearance (P<0.05), whereas the response during the other intensities was graded (100%=60%>40%>passive recovery, P<0.05). Active recovery after maximal all-out exercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner, with maximum clearance occurring at active recovery of 80% of lactate threshold.

28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

28 CFR 524.74 - Activities clearance.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

15 CFR 752.15 - Export clearance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Export clearance. 752.15 Section 752.15 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS SPECIAL...

15 CFR 752.15 - Export clearance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Export clearance. 752.15 Section 752.15 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS SPECIAL...

15 CFR 752.15 - Export clearance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Export clearance. 752.15 Section 752.15 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS SPECIAL...

20 CFR 653.501 - Requirements for accepting and processing clearance orders.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., DEPARTMENT OF LABOR SERVICES OF THE EMPLOYMENT SERVICE SYSTEM Agricultural Clearance Order Activity § 653.501... function of the job service as a no-fee labor exchange, that is, as a forum for bringing together employers... referred through the clearance system shall be notified to contact a local job service office, preferably...

20 CFR 653.501 - Requirements for accepting and processing clearance orders.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF LABOR SERVICES OF THE EMPLOYMENT SERVICE SYSTEM Agricultural Clearance Order Activity § 653.501... function of the job service as a no-fee labor exchange, that is, as a forum for bringing together employers... referred through the clearance system shall be notified to contact a local job service office, preferably...

Comparing taxi clearance input layouts for advancements in flight deck automation for surface operations

NASA Astrophysics Data System (ADS)

Cheng, Lara W. S.

Airport moving maps (AMMs) have been shown to decrease navigation errors, increase taxiing speed, and reduce workload when they depict airport layout, current aircraft position, and the cleared taxi route. However, current technologies are limited in their ability to depict the cleared taxi route due to the unavailability of datacomm or other means of electronically transmitting clearances from ATC to the flight deck. This study examined methods by which pilots can input ATC-issued taxi clearances to support taxi route depictions on the AMM. Sixteen general aviation (GA) pilots used a touchscreen monitor to input taxi clearances using two input layouts, softkeys and QWERTY, each with and without feedforward (graying out invalid inputs). QWERTY yielded more taxi route input errors than the softkeys layout. The presence of feedforward did not produce fewer taxi route input errors than in the non-feedforward condition. The QWERTY layout did reduce taxi clearance input times relative to the softkeys layout, but when feedforward was present this effect was observed only for the longer, 6-segment taxi clearances. It was observed that with the softkeys layout, feedforward reduced input times compared to non-feedforward but only for the 4-segment clearances. Feedforward did not support faster taxi clearance input times for the QWERTY layout. Based on the results and analyses of the present study, it is concluded that for taxi clearance inputs, (1) QWERTY remain the standard for alphanumeric inputs, and (2) feedforward be investigated further, with a focus on participant preference and performance of black-gray contrast of keys.

Parabolic quantitative structure-activity relationships and photodynamic therapy: application of a three-compartment model with clearance to the in vivo quantitative structure-activity relationships of a congeneric series of pyropheophorbide derivatives used as photosensitizers for photodynamic therapy.

PubMed

Potter, W R; Henderson, B W; Bellnier, D A; Pandey, R K; Vaughan, L A; Weishaupt, K R; Dougherty, T J

1999-11-01

An open three-compartment pharmacokinetic model was applied to the in vivo quantitative structure-activity relationship (QSAR) data of a homologous series of pyropheophorbide photosensitizers for photodynamic therapy (PDT). The physical model was a lipid compartment sandwiched between two identical aqueous compartments. The first compartment was assumed to clear irreversibly at a rate K0. The measured octanol-water partition coefficients, P(i) (where i is the number of carbons in the alkyl chain) and the clearance rate K0 determined the clearance kinetics of the drugs. Solving the coupled differential equations of the three-compartment model produced clearance kinetics for each of the sensitizers in each of the compartments. The third compartment was found to contain the target of PDT. This series of compounds is quite lipophilic. Therefore these drugs are found mainly in the second compartment. The drug level in the third compartment represents a small fraction of the tissue level and is thus not accessible to direct measurement by extraction. The second compartment of the model accurately predicted the clearance from the serum of mice of the hexyl ether of pyropheophorbide a, one member of this series of compounds. The diffusion and clearance rate constants were those found by fitting the pharmacokinetics of the third compartment to the QSAR data. This result validated the magnitude and mechanistic significance of the rate constants used to model the QSAR data. The PDT response to dose theory was applied to the kinetic behavior of the target compartment drug concentration. This produced a pharmacokinetic-based function connecting PDT response to dose as a function of time postinjection. This mechanistic dose-response function was fitted to published, single time point QSAR data for the pheophorbides. As a result, the PDT target threshold dose together with the predicted QSAR as a function of time postinjection was found.

Enoxacin decreases the clearance of theophylline in man.

PubMed Central

Wijnands, W J; Vree, T B; Van Herwaarden, C L

1985-01-01

In patients treated concurrently with theophylline and enoxacin, a new broad-spectrum antibacterial agent of the quinolone class, unexpectedly high plasma theophylline concentrations were measured. In part I of this study, daily plasma theophylline concentrations were measured in 14 patients. The mean +/- s.d. theophylline concentrations increased from 8.5 +/- 2.8 micrograms ml-1 prior to enoxacin to a maximum of 21.7 +/- 7.8 micrograms ml-1 during coadministration. In part II, six of these patients received aminophylline intravenously at a constant infusion rate and under controlled conditions. Plasma theophylline concentrations rose from 8.4 +/- 2.4 micrograms ml-1 prior to enoxacin treatment to 15.0 +/- 5.1 micrograms ml-1 at day 3 of coadministration (P less than 0.005). Plasma protein-binding and renal clearance of theophylline remained unchanged, whereas total body clearance of theophylline significantly decreased (P less than 0.005). From these observations it is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline. If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended. PMID:3867394

Lactate clearance as the predictor of outcome in pediatric septic shock.

PubMed

Choudhary, Richa; Sitaraman, Sadasivan; Choudhary, Anita

2017-01-01

Septic shock can rapidly evolve into multiple system organ failure and death. In the recent years, hyperlactatemia has been found to be a risk factor for mortality in critically ill adults. To evaluate the predictive value of lactate clearance and to determine the optimal cut-off value for predicting outcome in children with septic shock. A prospective observational study was performed on children with septic shock admitted to pediatric Intensive Care Unit (PICU). Serial lactate levels were measured at PICU admission, 24 and 48 h later. Lactate clearance, percent decrease in lactate level in 24 h, was calculated. The primary outcome measure was survival or nonsurvival at the end of hospital stay. We performed receiver operating characteristic analyses to calculate optimal cut-off values. The mean lactate levels at admission were significantly higher in the nonsurvivors than survivors, 5.12 ± 3.51 versus 3.13 ± 1.71 mmol/L ( P = 0.0001). The cut-off for lactate level at admission for the best prediction of mortality was determined as ≥4 mmol/L (odds ratio 5.4; 95% confidence interval [CI] =2.45-12.09). Mean lactate clearance was significantly higher in survivors than nonsurvivors (17.9 ± 39.9 vs. -23.2 ± 62.7; P < 0.0001). A lactate clearance rate of <10% at 24 h had a sensitivity and specificity of 78.7% and 72.2%, respectively and a positive predictive value of 83.1% for death. Failure to achieve a lactate clearance of more than 10% was associated with greater risk of mortality (likelihood ratio + 2.83; 95% CI = 1.82-4.41). Serial lactate levels can be used to predict outcome in pediatric septic shock. A 24 h lactate clearance cut-off of <10% is a predictor of in-hospital mortality in such patients.

Renal Clearance: Using an Interactive Activity to Visualize a Tricky Concept

ERIC Educational Resources Information Center

Hull, Kerry

2016-01-01

Renal clearance, the volume of blood cleared of a substance in a particular time period, is commonly recognized as one of the most difficult concepts in physiology. This difficulty may in part reflect the quantitative nature of renal clearance since many life sciences majors perceive that mathematics is irrelevant to their discipline. Students may…

14 CFR 105.17 - Flight visibility and clearance from cloud requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Flight visibility and clearance from cloud... Flight visibility and clearance from cloud requirements. No person may conduct a parachute operation, and...— (a) Into or through a cloud, or (b) When the flight visibility or the distance from any cloud is less...

14 CFR 105.17 - Flight visibility and clearance from cloud requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Flight visibility and clearance from cloud... Flight visibility and clearance from cloud requirements. No person may conduct a parachute operation, and...— (a) Into or through a cloud, or (b) When the flight visibility or the distance from any cloud is less...

14 CFR 105.17 - Flight visibility and clearance from cloud requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Flight visibility and clearance from cloud... Flight visibility and clearance from cloud requirements. No person may conduct a parachute operation, and...— (a) Into or through a cloud, or (b) When the flight visibility or the distance from any cloud is less...

14 CFR 105.17 - Flight visibility and clearance from cloud requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Flight visibility and clearance from cloud... Flight visibility and clearance from cloud requirements. No person may conduct a parachute operation, and...— (a) Into or through a cloud, or (b) When the flight visibility or the distance from any cloud is less...

14 CFR 105.17 - Flight visibility and clearance from cloud requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Flight visibility and clearance from cloud... Flight visibility and clearance from cloud requirements. No person may conduct a parachute operation, and...— (a) Into or through a cloud, or (b) When the flight visibility or the distance from any cloud is less...

Transitional probability-based model for HPV clearance in HIV-1-positive adolescent females.

PubMed

Kravchenko, Julia; Akushevich, Igor; Sudenga, Staci L; Wilson, Craig M; Levitan, Emily B; Shrestha, Sadeep

2012-01-01

HIV-1-positive patients clear the human papillomavirus (HPV) infection less frequently than HIV-1-negative. Datasets for estimating HPV clearance probability often have irregular measurements of HPV status and risk factors. A new transitional probability-based model for estimation of probability of HPV clearance was developed to fully incorporate information on HIV-1-related clinical data, such as CD4 counts, HIV-1 viral load (VL), highly active antiretroviral therapy (HAART), and risk factors (measured quarterly), and HPV infection status (measured at 6-month intervals). Data from 266 HIV-1-positive and 134 at-risk HIV-1-negative adolescent females from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort were used in this study. First, the associations were evaluated using the Cox proportional hazard model, and the variables that demonstrated significant effects on HPV clearance were included in transitional probability models. The new model established the efficacy of CD4 cell counts as a main clearance predictor for all type-specific HPV phylogenetic groups. The 3-month probability of HPV clearance in HIV-1-infected patients significantly increased with increasing CD4 counts for HPV16/16-like (p<0.001), HPV18/18-like (p<0.001), HPV56/56-like (p = 0.05), and low-risk HPV (p<0.001) phylogenetic groups, with the lowest probability found for HPV16/16-like infections (21.60±1.81% at CD4 level 200 cells/mm(3), p<0.05; and 28.03±1.47% at CD4 level 500 cells/mm(3)). HIV-1 VL was a significant predictor for clearance of low-risk HPV infections (p<0.05). HAART (with protease inhibitor) was significant predictor of probability of HPV16 clearance (p<0.05). HPV16/16-like and HPV18/18-like groups showed heterogeneity (p<0.05) in terms of how CD4 counts, HIV VL, and HAART affected probability of clearance of each HPV infection. This new model predicts the 3-month probability of HPV infection clearance based on CD4 cell counts and other HIV-1-related

10 CFR 10.21 - Suspension of access authorization and/or employment clearance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... ELIGIBILITY FOR ACCESS TO RESTRICTED DATA OR NATIONAL SECURITY INFORMATION OR AN EMPLOYMENT CLEARANCE... access authorization and/or an employment clearance, the Director, Division of Facilities and Security... Corporate Management and Chief Information Officer or other Deputy Executive Director, his or her...

10 CFR 10.21 - Suspension of access authorization and/or employment clearance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... ELIGIBILITY FOR ACCESS TO RESTRICTED DATA OR NATIONAL SECURITY INFORMATION OR AN EMPLOYMENT CLEARANCE... access authorization and/or an employment clearance, the Director, Division of Facilities and Security... Corporate Management and Chief Information Officer or other Deputy Executive Director, his or her...

Morphine clearance in children: does race or genetics matter?

PubMed

Sadhasivam, Senthilkumar; Krekels, Elke H J; Chidambaran, Vidya; Esslinger, Hope R; Ngamprasertwong, Pornswan; Zhang, Kejian; Fukuda, Tsuyoshi; Vinks, Alexander A

2012-01-01

Interindividual variability in analgesic response and adverse effects of opioids because of narrow therapeutic indices are major clinical problems. Morphine is an opioid commonly used in children to manage perioperative pain. Al-though size and age often are considered primary covariates for morphine pharmacokinetic models, the impact of other factors important in personalizing care such as race and genetic variations on morphine disposition is not well documented. Genotype blinded clinical observational pharmacokinetic study. One hundred forty-six African American and Caucasian children scheduled for elective outpatient adenotonsillectomy were enrolled in our prospective genotype blinded observational study with standard perioperative clinical care. Tertiary care pediatric institution. Morphine bolus for intraoperative analgesia in children and pharmacokinetic analyses in different races. Pharmacokinetics and pharmacogenetics of intravenous morphine in a homogeneous pediatric outpatient surgical pain population were evaluated. The authors observed that African American children have higher morphine clearance than Caucasian children. The increased clearance is directed toward the formation of morphine-3-glucuronide formation, rather than the formation of morphine-6-glucuronide. Common uridine diphosphate glucuronosyl transferase (UGT) 2B7 genetic variations (2161C>T and 802C>T) were not associated with observed racial differences in morphine's clearance although the wild type of the UGT2B7 isozyme is more prevalent in the African Americans. Race of the child is an important factor in perioperative intravenous morphine's clearance and its potential role in personalizing analgesia with morphine needs further investigation.

Dual roles for hepatic lectin receptors in the clearance of chilled platelets.

PubMed

Rumjantseva, Viktoria; Grewal, Prabhjit K; Wandall, Hans H; Josefsson, Emma C; Sørensen, Anne Louise; Larson, Göran; Marth, Jamey D; Hartwig, John H; Hoffmeister, Karin M

2009-11-01

Rapid chilling causes glycoprotein-Ib (GPIb) receptors to cluster on blood platelets. Hepatic macrophage beta(2) integrin binding to beta-N-acetylglucosamine (beta-GlcNAc) residues in the clusters leads to rapid clearance of acutely chilled platelets after transfusion. Although capping the beta-GlcNAc moieties by galactosylation prevents clearance of short-term-cooled platelets, this strategy is ineffective after prolonged refrigeration. We report here that prolonged refrigeration increased the density and concentration of exposed galactose residues on platelets such that hepatocytes, through Ashwell-Morell receptor binding, become increasingly involved in platelet removal. Macrophages rapidly removed a large fraction of transfused platelets independent of their storage conditions. With prolonged platelet chilling, hepatocyte-dependent clearance further diminishes platelet recovery and survival after transfusion. Inhibition of chilled platelet clearance by both beta(2) integrin and Ashwell-Morell receptors may afford a potentially simple method for storing platelets in the cold.

A prototype wireless inertial-sensing device for measuring toe clearance.

PubMed

Lai, Daniel T H; Charry, E; Begg, R; Palaniswami, M

2008-01-01

Tripping and slipping are serious health concerns for the elderly because they result in life threatening injuries i.e., fractures and high medical costs. Our recent work in detection of tripping gait patterns has demonstrated that minimum toe clearance (MTC) is a sensitive falls risk predictor. MTC measurement has previously been done in gait laboratories and on treadmills which potentially imposes controlled walking conditions. In this paper, we describe a prototype design of a wireless device for monitoring vertical toe clearance. The sensors consists of a tri-axis accelerometer and dual-axis gyroscope connected to Crossbow sensor motes for wireless data transmission. Sensor data are transmitted to a laptop and displayed on a Matlab graphic user interface (GUI). We have performed zero base and treadmill experiments to investigate sensor performance to environmental variations and compared the calculated toe clearance against measurements made by an Optotrak motion system. It was found that device outputs were approximately independent of small ambient temperature variations, had a reliable range of 20m indoors and 50m outdoors and a maximum transmission rate of 20 packets/s. Toe clearance measurements were found to follow the Optotrak measurement trend but could be improved further by dealing with double integration errors and improving data transmission rates.

Deposition, retention, and clearance of inhaled particles.

PubMed Central

Lippmann, M; Yeates, D B; Albert, R E

1980-01-01

The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from

In vivo toxicity, biodistribution, and clearance of glutathione-coated gold nanoparticles.

PubMed

Simpson, Carrie A; Salleng, Kenneth J; Cliffel, David E; Feldheim, Daniel L

2013-02-01

Gold nanoparticles are emerging as promising materials from which to construct nanoscale therapeutics and therapeutic delivery systems. However, animal studies have shown that gold nanoparticles modified with certain thiol monolayers such as tiopronin can cause renal complications and morbidity. Although these effects may be eliminated by coadsorbing small amounts of polyethylene glycol (PEG) onto the nanoparticle surface, PEG can also lower cellular internalization efficiency and binding interactions with protein disease targets, significantly reducing the potential for using gold nanoparticles as therapeutics. Using ICP-MS analysis of blood, urine, and several organs, we show in this article that glutathione-coated gold nanoparticles (1.2 nm ± 0.9 nm) cause no morbidity at any concentration up to and including 60 μM and target primary organs although providing gradual dissipation and clearance over time. This study suggests that glutathione may be an attractive alternative to PEG in the design of gold nanoparticle therapeutics. This study describes the utility and toxicity of glutathione coated gold nanoparticles in comparison to PEGylated counterparts that are commonly used to increase "Stealth" properties and lower cytotoxicity. Too much PEG on the NPs can lead to lower cellular internalization efficiency and less efficient binding interactions with protein disease targets, significantly reducing the potential for using gold nanoparticles as therapeutics. Copyright © 2013 Elsevier Inc. All rights reserved.

Targeted Therapies in NSCLC: Emerging oncogene targets following the success of EGFR

PubMed Central

Berge, Eamon M; Doebele, Robert C

2014-01-01

The diagnostic testing, treatment and prognosis of non-small cell lung cancer (NSCLC) has undergone a paradigm shift since the discovery of sensitizing mutations in the epidermal growth factor receptor (EGFR) gene in a subset of NSCLC patients. Several additional oncogenic mutations, including gene fusions and amplifications have since been discovered, with a number of drugs that target each specific oncogene. This review focuses on oncogenes in NSCLC other than EGFR and their companion ‘targeted therapies’. Particular emphasis is placed on the role of ALK, ROS1, RET, MET, BRAF, and HER2 in NSCLC. PMID:24565585

Turbomachinery Clearance Control

NASA Technical Reports Server (NTRS)

Chupp, Raymond E.; Hendricks, Robert C.; Lattime, Scott B.; Steinetz, Bruce M.; Aksit, Mahmut F.

2007-01-01

Controlling interface clearances is the most cost effective method of enhancing turbomachinery performance. Seals control turbomachinery leakages, coolant flows and contribute to overall system rotordynamic stability. In many instances, sealing interfaces and coatings are sacrificial, like lubricants, giving up their integrity for the benefit of the component. They are subjected to abrasion, erosion, oxidation, incursive rubs, foreign object damage (FOD) and deposits as well as extremes in thermal, mechanical, aerodynamic and impact loadings. Tribological pairing of materials control how well and how long these interfaces will be effective in controlling flow. A variety of seal types and materials are required to satisfy turbomachinery sealing demands. These seals must be properly designed to maintain the interface clearances. In some cases, this will mean machining adjacent surfaces, yet in many other applications, coatings are employed for optimum performance. Many seals are coating composites fabricated on superstructures or substrates that are coated with sacrificial materials which can be refurbished either in situ or by removal, stripping, recoating and replacing until substrate life is exceeded. For blade and knife tip sealing an important class of materials known as abradables permit blade or knife rubbing without significant damage or wear to the rotating element while maintaining an effective sealing interface. Most such tip interfaces are passive, yet some, as for the high-pressure turbine (HPT) case or shroud, are actively controlled. This work presents an overview of turbomachinery sealing. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues.

Nano-Advantage in Enhanced Drug Delivery with Biodegradable Nanoparticles: Contribution of Reduced Clearance

PubMed Central

Kadam, Rajendra S.; Bourne, David W. A.

2012-01-01

The aim of this study was to investigate the contribution of reduced apparent clearance to the enhanced exposure reported for biodegradable nanoparticles after extravascular and intravascular routes of administration. Plasma concentration profiles for drug and nanoparticle formulations after administration by intravenous, intraduodenal, and oral routes were extracted from the literature. Data were fit to pharmacokinetic models using BOOMER. The compartmental pharmacokinetic analysis of literature data for six drugs (camptothecin, 9-nitrocamptothecin, epirubicin, vinpocetine, clozapine, and cyclosporine) showed that the encapsulation of drug molecules in nanoparticles significantly reduced the apparent clearance and prolonged the apparent circulation half-life compared with those for the plain drug. Positively charged nanoparticles assessed in this study had lower apparent clearance, lower elimination rate constant values, and longer apparent circulation half-life than neutral and negatively charged nanoparticles. After oral administration, a reduction in apparent clearance contributed substantially to elevations in plasma drug exposure with nanoparticles. For the drugs and delivery systems examined, the nano-advantage in drug delivery enhancement can be explained, in part, by reduced clearance. PMID:22498894

Identifying Minefields and Verifying Clearance: Adapting Statistical Methods for UXO Target Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilbert, Richard O.; O'Brien, Robert F.; Wilson, John E.

2003-09-01

It may not be feasible to completely survey large tracts of land suspected of containing minefields. It is desirable to develop a characterization protocol that will confidently identify minefields within these large land tracts if they exist. Naturally, surveying areas of greatest concern and most likely locations would be necessary but will not provide the needed confidence that an unknown minefield had not eluded detection. Once minefields are detected, methods are needed to bound the area that will require detailed mine detection surveys. The US Department of Defense Strategic Environmental Research and Development Program (SERDP) is sponsoring the development ofmore » statistical survey methods and tools for detecting potential UXO targets. These methods may be directly applicable to demining efforts. Statistical methods are employed to determine the optimal geophysical survey transect spacing to have confidence of detecting target areas of a critical size, shape, and anomaly density. Other methods under development determine the proportion of a land area that must be surveyed to confidently conclude that there are no UXO present. Adaptive sampling schemes are also being developed as an approach for bounding the target areas. These methods and tools will be presented and the status of relevant research in this area will be discussed.« less

High-Clearance Six-Wheel Suspension

NASA Technical Reports Server (NTRS)

Bickler, Donald B.

1992-01-01

Multilevered suspension system gives body of vehicle high clearance and allows wheels to be steered independently. Suspension linkages above wheels enable body to skim over obstacles as high as wheel. Levers and independently steered wheels enable vehicle to climb steps 1 1/2 wheel diameters high and cross gaps 1 3/4 wide. Adaptable to off-the-road recreational vehicles, military scout vehicles, and robotic emergency vehicles.

A Novel Clinically Translatable Fluorescent Nanoparticle for Targeted Molecular Imaging of Tumors in Living Subjects

PubMed Central

Gao, Jinhao; Chen, Kai; Luong, Richard; Bouley, Donna M.; Mao, Hua; Qiao, Tiecheng; Gambhir, Sanjiv S.; Cheng, Zhen

2011-01-01

The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QDs as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding non-tumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD2 to integrin αvβ3–positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron based nanoprobes in the clinical setting in the near future. PMID:22172022

A novel clinically translatable fluorescent nanoparticle for targeted molecular imaging of tumors in living subjects.

PubMed

Gao, Jinhao; Chen, Kai; Luong, Richard; Bouley, Donna M; Mao, Hua; Qiao, Tiecheng; Gambhir, Sanjiv S; Cheng, Zhen

2012-01-11

The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QD as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance, and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding nontumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD(2) to integrin α(v)β(3)-positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD-modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron-based nanoprobes in the clinical setting in the near future. © 2011 American Chemical Society

The tribological behaviour of different clearance MOM hip joints with lubricants of physiological viscosities.

PubMed

Hu, X Q; Wood, R J K; Taylor, A; Tuke, M A

2011-11-01

Clearance is one of the most influential parameters on the tribological performance of metal-on-metal (MOM) hip joints and its selection is a subject of considerable debate. The objective of this paper is to study the lubrication behaviour of different clearances for MOM hip joints within the range of human physiological and pathological fluid viscosities. The frictional torques developed by MOM hip joints with a 50 mm diameter were measured for both virgin surfaces and during a wear simulator test. Joints were manufactured with three different diametral clearances: 20, 100, and 200 microm. The fluid used for the friction measurements which contained different ratios of 25 percent newborn calf serum and carboxymethyl cellulose (CMC) with the obtained viscosities values ranging from 0.001 to 0.71 Pa s. The obtained results indicate that the frictional torque for the 20 microm clearance joint remains high over the whole range of the viscosity values. The frictional torque of the 100 microm clearance joint was low for the very low viscosity (0.001 Pa s) lubricant, but increased with increasing viscosity value. The frictional torque of the 200 microm clearance joint was high at very low viscosity levels, however, it reduced with increasing viscosity. It is concluded that a smaller clearance level can enhance the formation of an elastohydrodynamic lubrication (EHL) film, but this is at the cost of preventing fluid recovery between the bearing surfaces during the unloaded phase of walking. Larger clearance bearings allow a better recovery of lubricant during the unloaded phase, which is necessary for higher viscosity lubricants. The selection of the clearance value should therefore consider both the formation of the EHL film and the fluid recovery as a function of the physiological viscosity in order to get an optimal tribological performance for MOM hip joints. The application of either 25 per cent bovine serum or water in existing in vitro tribological study should

5 CFR 1320.11 - Clearance of collections of information in proposed rules.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Clearance of collections of information in proposed rules. 1320.11 Section 1320.11 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES CONTROLLING PAPERWORK BURDENS ON THE PUBLIC § 1320.11 Clearance of collections of...

5 CFR 1320.12 - Clearance of collections of information in current rules.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Clearance of collections of information in current rules. 1320.12 Section 1320.12 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES CONTROLLING PAPERWORK BURDENS ON THE PUBLIC § 1320.12 Clearance of collections of...

Proficiency testing criteria for clearance level in solid waste gamma measurement in Taiwan.

PubMed

Chen, Chun-Liang; Wang, Jeng-Jong; Chiu, Huang-Sheng

2013-11-01

To guarantee the measurement quality for clearance level in solid waste material, the Institute of Nuclear Energy Research (INER) established the criteria for proficiency testing of clearance level measurement. INER and the Taiwan Accreditation Foundation (TAF) organized the Technique Committee Meeting twice to discuss these criteria in 2011. The participating laboratories must completely conform to the ISO/IEC 17025, and they also must meet the requirements of the criteria. According to the criteria, the participating laboratories analyzed the minimum detectable amount (MDA) and that should be less than 20% of the clearance level (AMDA) given in the Atomic Energy Council's (AEC) "Regulations on Clearance Level for Radioactive Waste Management". The testing results should conform to the deviation and traceability requirements. Copyright © 2013 Elsevier Ltd. All rights reserved.

Surface code—biophysical signals for apoptotic cell clearance

NASA Astrophysics Data System (ADS)

Biermann, Mona; Maueröder, Christian; Brauner, Jan M.; Chaurio, Ricardo; Janko, Christina; Herrmann, Martin; Muñoz, Luis E.

2013-12-01

Apoptotic cell death and the clearance of dying cells play an important and physiological role in embryonic development and normal tissue turnover. In contrast to necrosis, apoptosis proceeds in an anti-inflammatory manner. It is orchestrated by the timed release and/or exposure of so-called ‘find-me’, ‘eat me’ and ‘tolerate me’ signals. Mononuclear phagocytes are attracted by various ‘find-me’ signals, including proteins, nucleotides, and phospholipids released by the dying cell, whereas the involvement of granulocytes is prevented via ‘stay away’ signals. The exposure of anionic phospholipids like phosphatidylserine (PS) by apoptotic cells on the outer leaflet of the plasma membrane is one of the main ‘eat me’ signals. PS is recognized by a number of innate receptors as well as by soluble bridging molecules on the surface of phagocytes. Importantly, phagocytes are able to discriminate between viable and apoptotic cells both exposing PS. Due to cytoskeleton remodeling PS has a higher lateral mobility on the surfaces of apoptotic cells thereby promoting receptor clustering on the phagocyte. PS not only plays an important role in the engulfment process, but also acts as ‘tolerate me’ signal inducing the release of anti-inflammatory cytokines by phagocytes. An efficient and fast clearance of apoptotic cells is required to prevent secondary necrosis and leakage of intracellular danger signals into the surrounding tissue. Failure or prolongation of the clearance process leads to the release of intracellular antigens into the periphery provoking inflammation and development of systemic inflammatory autoimmune disease like systemic lupus erythematosus. Here we review the current findings concerning apoptosis-inducing pathways, important players of apoptotic cell recognition and clearance as well as the role of membrane remodeling in the engulfment of apoptotic cells by phagocytes.

32 CFR 154.16 - Security clearance.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Security clearance. 154.16 Section 154.16 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE... immigrant alien or a foreign national in furtherance of the mission of the Department of Defense, such...

32 CFR 154.16 - Security clearance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false Security clearance. 154.16 Section 154.16 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE... immigrant alien or a foreign national in furtherance of the mission of the Department of Defense, such...

32 CFR 154.16 - Security clearance.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Security clearance. 154.16 Section 154.16 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE... immigrant alien or a foreign national in furtherance of the mission of the Department of Defense, such...

32 CFR 154.16 - Security clearance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Security clearance. 154.16 Section 154.16 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE... immigrant alien or a foreign national in furtherance of the mission of the Department of Defense, such...

32 CFR 154.16 - Security clearance.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false Security clearance. 154.16 Section 154.16 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE... immigrant alien or a foreign national in furtherance of the mission of the Department of Defense, such...

Rate-Based Model Predictive Control of Turbofan Engine Clearance

NASA Technical Reports Server (NTRS)

DeCastro, Jonathan A.

2006-01-01

An innovative model predictive control strategy is developed for control of nonlinear aircraft propulsion systems and sub-systems. At the heart of the controller is a rate-based linear parameter-varying model that propagates the state derivatives across the prediction horizon, extending prediction fidelity to transient regimes where conventional models begin to lose validity. The new control law is applied to a demanding active clearance control application, where the objectives are to tightly regulate blade tip clearances and also anticipate and avoid detrimental blade-shroud rub occurrences by optimally maintaining a predefined minimum clearance. Simulation results verify that the rate-based controller is capable of satisfying the objectives during realistic flight scenarios where both a conventional Jacobian-based model predictive control law and an unconstrained linear-quadratic optimal controller are incapable of doing so. The controller is evaluated using a variety of different actuators, illustrating the efficacy and versatility of the control approach. It is concluded that the new strategy has promise for this and other nonlinear aerospace applications that place high importance on the attainment of control objectives during transient regimes.

A parameters optimization method for planar joint clearance model and its application for dynamics simulation of reciprocating compressor

NASA Astrophysics Data System (ADS)

Hai-yang, Zhao; Min-qiang, Xu; Jin-dong, Wang; Yong-bo, Li

2015-05-01

In order to improve the accuracy of dynamics response simulation for mechanism with joint clearance, a parameter optimization method for planar joint clearance contact force model was presented in this paper, and the optimized parameters were applied to the dynamics response simulation for mechanism with oversized joint clearance fault. By studying the effect of increased clearance on the parameters of joint clearance contact force model, the relation of model parameters between different clearances was concluded. Then the dynamic equation of a two-stage reciprocating compressor with four joint clearances was developed using Lagrange method, and a multi-body dynamic model built in ADAMS software was used to solve this equation. To obtain a simulated dynamic response much closer to that of experimental tests, the parameters of joint clearance model, instead of using the designed values, were optimized by genetic algorithms approach. Finally, the optimized parameters were applied to simulate the dynamics response of model with oversized joint clearance fault according to the concluded parameter relation. The dynamics response of experimental test verified the effectiveness of this application.

ELMO1 Regulates Autophagy Induction and Bacterial Clearance During Enteric Infection.

PubMed

Sarkar, Arup; Tindle, Courtney; Pranadinata, Rama F; Reed, Sharon; Eckmann, Lars; Stappenbeck, Thaddeus S; Ernst, Peter B; Das, Soumita

2017-12-19

Macrophages are specialized phagocytic cells involved in clearing invading pathogens. Previously we reported that engulfment and cell motility protein 1 (ELMO1) in macrophages mediates bacterial internalization and intestinal inflammation. Here we studied the role of ELMO1 in the fate of internalized targets. ELMO1 is present in the intracellular vesicles and enhances accumulation of the protein LC3B following engulfment of Salmonella or treatment with autophagy-inducing rapamycin. The protein ATG5 and the kinase ULK1 are involved in classical autophagy, while LC3-associated phagocytosis is ULK1 independent. ATG5 but not ULK1 cooperated with ELMO1 in LC3 accumulation after infection, suggesting the ELMO1 preferentially regulated LC3-associated phagocytosis. Because LC3-associated phagocytosis delivers cargo for degradation, the contribution of ELMO1 to the lysosome degradation pathways was evaluated by studying pH and cathepsin B activity. ELMO1-depleted macrophages showed a time-dependent increase in pH and a decrease in cathepsin B activity associated with bacterial survival. Together, ELMO1 regulates LC3B accumulation and antimicrobial responses involved in the clearance of enteric pathogens. This paper investigated how innate immune pathways involving ELMO1 work in a coordinated fashion to eliminate bacterial threats. ELMO1 is present in the phagosome and enhances bacterial clearance by differential regulation of lysosomal acidification and enzymatic activity. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Clearance Properties of Nano-sized Particles and Molecules as Imaging Agents: Considerations and Caveats

PubMed Central

Longmire, Michelle; Choyke, Peter L.; Kobayashi, Hisataka

2009-01-01

Summary Nanoparticles possess enormous potential as diagnostic imaging agents and hold promise for the development of multimodality agents with both imaging and therapeutic capabilities. Yet, some of the most promising nanoparticles demonstrate prolonged tissue retention and contain heavy metals. This presents serious concerns for toxicity. The creation of nanoparticles with optimal clearance characteristics will minimize toxicity risks by reducing the duration of exposure to these agents. Given that many nanoparticles possess easily modifiable surface and interior chemistry, if nanoparticle characteristics associated with optimal clearance from the body were well established, it would be feasible to design and create agents with more favorable clearance properties. This paper presents a thorough discussion of the physiologic aspects of nanoparticle clearance, focusing on renal mechanisms, as well as provides an overview of current research investigating clearance of specific types of nanoparticles and nano-sized macromolecules, including dendrimers, quantum dots, liposomes and carbon, gold, and silica-based nanoparticles. PMID:18817471

Oral sugar clearance and root caries prevalence in rheumatic patients with dry mouth symptoms.

PubMed

Risheim, H; Arneberg, P; Birkhed, D

1992-01-01

The relationship between root caries, oral sugar clearance, salivary flow rate, and salivary counts of mutans streptococci, lactobacilli and candida has been studied in a group of 22 rheumatic patients (age range 40-72 years). The study group comprised all subjects volunteering for a clinical trial on relief of dry mouth symptoms. The median salivary flow was 0.09 ml/min at rest and 0.9 ml/min during chewing stimulation. The median sugar clearance time was about 5 min in the sublingual area and 16 min in the lower buccal vestibule. For subjects with 0-2 root caries lesions the clearance time at both sites was shorter than for subjects with 3 or more lesions (p < 0.05). A long oral clearance time was significantly correlated with age, root caries (DS and DFS), low resting salivary flow, and high salivary counts of mutans streptococci. It is concluded that root caries in rheumatic patients with low salivary flow is significantly related to oral sugar clearance time.

10 CFR 10.21 - Suspension of access authorization and/or employment clearance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Suspension of access authorization and/or employment clearance. 10.21 Section 10.21 Energy NUCLEAR REGULATORY COMMISSION CRITERIA AND PROCEDURES FOR DETERMINING... Procedures § 10.21 Suspension of access authorization and/or employment clearance. In those cases where...

10 CFR 10.21 - Suspension of access authorization and/or employment clearance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Suspension of access authorization and/or employment clearance. 10.21 Section 10.21 Energy NUCLEAR REGULATORY COMMISSION CRITERIA AND PROCEDURES FOR DETERMINING... Procedures § 10.21 Suspension of access authorization and/or employment clearance. In those cases where...

10 CFR 10.21 - Suspension of access authorization and/or employment clearance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Suspension of access authorization and/or employment clearance. 10.21 Section 10.21 Energy NUCLEAR REGULATORY COMMISSION CRITERIA AND PROCEDURES FOR DETERMINING... Procedures § 10.21 Suspension of access authorization and/or employment clearance. In those cases where...

49 CFR 236.73 - Open-wire transmission line; clearance to other circuits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Open-wire transmission line; clearance to other..., AND APPLIANCES Rules and Instructions: All Systems Wires and Cables § 236.73 Open-wire transmission line; clearance to other circuits. Open-wire transmission line operating at voltage of 750 volts or...

49 CFR 236.73 - Open-wire transmission line; clearance to other circuits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Open-wire transmission line; clearance to other..., AND APPLIANCES Rules and Instructions: All Systems Wires and Cables § 236.73 Open-wire transmission line; clearance to other circuits. Open-wire transmission line operating at voltage of 750 volts or...

Targeted alpha therapy using short-lived alpha-particles and the promise of nanobodies as targeting vehicle

PubMed Central

Dekempeneer, Yana; Keyaerts, Marleen; Krasniqi, Ahmet; Puttemans, Janik; Muyldermans, Serge; Lahoutte, Tony; D’huyvetter, Matthias; Devoogdt, Nick

2016-01-01

ABSTRACT Introduction: The combination of a targeted biomolecule that specifically defines the target and a radionuclide that delivers a cytotoxic payload offers a specific way to destroy cancer cells. Targeted radionuclide therapy (TRNT) aims to deliver cytotoxic radiation to cancer cells and causes minimal toxicity to surrounding healthy tissues. Recent advances using α-particle radiation emphasizes their potential to generate radiation in a highly localized and toxic manner because of their high level of ionization and short range in tissue. Areas covered: We review the importance of targeted alpha therapy (TAT) and focus on nanobodies as potential beneficial vehicles. In recent years, nanobodies have been evaluated intensively as unique antigen-specific vehicles for molecular imaging and TRNT. Expert opinion: We expect that the efficient targeting capacity and fast clearance of nanobodies offer a high potential for TAT. More particularly, we argue that the nanobodies’ pharmacokinetic properties match perfectly with the interesting decay properties of the short-lived α-particle emitting radionuclides Astatine-211 and Bismuth-213 and offer an interesting treatment option particularly for micrometastatic cancer and residual disease. PMID:27145158

Effect of Turbine Axial Nozzle-Wheel Clearance on Performance of Mark 25 Torpedo Power Plant

NASA Technical Reports Server (NTRS)

Hoyt, Jack W.; Kottas, Harry

1948-01-01

Investigations were made of the turbine from a Mark 25 torpedo to determine the performance of the unit with three different turbine nozzles at various axial nozzle-wheel clearances. Turbine efficiency with a reamed nondivergent nozzle that uses the axial clearance space for gas expansion was little affected by increasing the axial running clearance from 0.030 to 0.150 inch. Turbine efficiency with cast nozzles that expanded the gas inside the nozzle passage was found to be sensitive to increased axial nozzle-wheel clearance. A cast nozzle giving a turbine brake efficiency of 0.525 at an axial running clearance of 0.035 inch gave a brake efficiency of 0.475 when the clearance was increased to 0.095 inch for the same inlet-gas conditions and blade-jet speed ratio. If the basis for computing the isentropic power available to the turbine is the temperature inside the nozzle rather then the temperature in the inlet-gas pipe, an increase in turbine efficiency of about 0.01 is indicated.

Applying Organ Clearance Concepts in a Clinical Setting

PubMed Central

2008-01-01

Objective To teach doctor of pharmacy (PharmD) students how to apply organ clearance concepts in a clinical setting in order to optimize dose management, select the right drug product, and promote better patient-centered care practices. Design A student-focused 5-hour topic entitled "Organ Clearance Concepts: Modeling and Clinical Applications" was developed and delivered to second-year PharmD students. Active-learning techniques, such as reading assignments and thought-provoking questions, and collaborative learning techniques, such as small groups, were used. Student learning was assessed using application cards and a minute paper. Assessment Overall student responses to topic presentation were overwhelmingly positive. The teaching strategies here discussed allowed students to play an active role in their own learning process and provided the necessary connection to keep them motivated, as mentioned in the application cards and minute paper assessments. Students scored an average of 88% on the examination given at the end of the course. Conclusion By incorporating active-learning and collaborative-learning techniques in presenting material on organ clearance concept, students gained a more thorough knowledge of dose management and drug-drug interactions than if the concepts had been presented using a traditional lecture format. This knowledge will help students in solving critical patient situations in a real-world context. PMID:19214275

Active Piezoelectric Structures for Tip Clearance Management Assessed

NASA Technical Reports Server (NTRS)

1995-01-01

Managing blade tip clearance in turbomachinery stages is critical to developing advanced subsonic propulsion systems. Active casing structures with embedded piezoelectric actuators appear to be a promising solution. They can control static and dynamic tip clearance, compensate for uneven deflections, and accomplish electromechanical coupling at the material level. In addition, they have a compact design. To assess the feasibility of this concept and assist the development of these novel structures, the NASA Lewis Research Center developed in-house computational capabilities for composite structures with piezoelectric actuators and sensors, and subsequently used them to simulate candidate active casing structures. The simulations indicated the potential of active casings to modify the blade tip clearance enough to improve stage efficiency. They also provided valuable design information, such as preliminary actuator configurations (number and location) and the corresponding voltage patterns required to compensate for uneven casing deformations. An active ovalization of a casing with four discrete piezoceramic actuators attached on the outer surface is shown. The center figure shows the predicted radial displacements along the hoop direction that are induced when electrostatic voltage is applied at the piezoceramic actuators. This work, which has demonstrated the capabilities of in-house computational models to analyze and design active casing structures, is expected to contribute toward the development of advanced subsonic engines.

Measurement method of rotation angle and clearance in intelligent spherical hinge

NASA Astrophysics Data System (ADS)

Hu, Penghao; Lu, Yichang; Chen, Shiyi; Hu, Yi; Zhu, Lianqing

2018-06-01

Precision ball hinges are widely applied in parallel mechanisms, robotics, and other areas, but their rotation orientation and angle cannot be obtained during passive motion. The simultaneous clearance error in a precision ball hinge’s motion also can not be determined. In this paper we propose an intelligent ball hinge (IBH) that can detect the rotation angle and moving clearance, based on our previous research results. The measurement model was optimized to promote measurement accuracy and resolution, and an optimal design for the IBH’s structure was determined. The experimental data showed that the measurement accuracy and resolution of the modified scheme were improved. Within  ±10° and  ±  20°, the average errors of the uniaxial measurements were 0.29° and 0.42°, respectively. The resolution of the measurements was 15″. The source of the measurement errors was analyzed through theory and experimental data and several key error sources were determined. A point capacitance model for measuring the clearance error is proposed, which is useful not only in compensating for the angle measurement error but also in realizing the motion clearance of an IBH in real-time.

Integrating the Clearance in NPP Residual Material Management

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia-Bermejo, R.; Lamela, B.

Previous Experiences in decommissioning projects are being used to optimize the residual material management in NPP, metallic scrap usually. The approach is based in the availability of a materials Clearance MARSSIM-based methodology developed and licensed in Spain. A typical project includes the integration of segregation, decontamination, clearance, quality control and quality assurance activities. The design is based in the clearance methodology features translating them into standard operational procedures. In terms of ecological taxes and final disposal costs, significant amounts of money could be saved with this type of approaches. The last clearance project managed a total amount of 405 tonsmore » scrap metal and a similar amount of other residual materials occupying a volume of 1500 m{sup 3}. After less than a year of field works 251 tons were finally recycled in a non-licensed smelting facility. The balance was disposed as LILW. In the planning phase the estimated cost savings were 4.5 Meuro. However, today a VLLW option is available in European countries so, the estimated cost savings are reduced to 1.2 Meuro. In conclusion: the application of materials clearance in NPP decommissioning lessons learnt to the NPP residual material management is an interesting management option. This practice is currently going on in Spanish NPP and, in a preliminary view, is consistent with the new MARSAME Draft. An interesting parameter is the cost of 1 m3 of recyclable scrap. The above estimates are very project specific because in the segregation process other residual materials were involved. If the effect of this other materials is removed the estimated Unit Cost were in this project around 1700 euro/m{sup 3}, this figure is clearly below the above VLLW disposal cost of 2600 euro. In a future project it appears feasible to descend to 839 euro/m{sup 3} and if it became routine values and is used in big Decommissioning projects, around 600 euro/m{sup 3} or below

Application of chromatic confocal displacement sensor in measurement of tip clearance

NASA Astrophysics Data System (ADS)

Bi, Chao; Li, Di; Fang, Jianguo; Zhang, Bin

2016-10-01

In the field of aeronautics, the tip clearance of rotor exerts a crucial influence on the performance of the aero engine. As defined as the radial distance between the top of the blade and the inner wall of the casing, the tip clearance of too large or small size will adversely affect the normal running of the engine. In order to realize accurate measurement of the tip clearance in a simple way, a non-contact measuring method by the chromatic confocal displacement sensor is proposed in the paper. The sensor possesses the advantages such as small volume, good signal-to-noise ratio, high accuracy and response frequency etc., which make it be widely used in engineering and industry. For testing the performance and potential application of the sensor, a simulation testing platform is established. In the platform, a simulation blisk is installed on the air bearing spindle and a chromatic confocal displacement sensor is fixed on the platform to measure the displacement variation of the blade tip, which can be used to characterize the variation of the tip clearance. In the simulation experiments, both of single and continuous measurement of the tip clearance of the 36 blades on the blisk is executed. As the results of experiments show, the chromatic confocal displacement sensor can meet the requirements of measuring task, in which both of high measuring efficiency and accuracy could be achieved. Therefore, the measuring method proposed in the paper can be utilized in the actual assembling sites of the aero engine.

Fenofibrate Decreases Insulin Clearance and Insulin Secretion to Maintain Insulin Sensitivity*

PubMed Central

Ramakrishnan, Sadeesh K.; Russo, Lucia; Ghanem, Simona S.; Patel, Payal R.; Oyarce, Ana Maria; Heinrich, Garrett; Najjar, Sonia M.

2016-01-01

High fat diet reduces the expression of CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a transmembrane glycoprotein that promotes insulin clearance and down-regulates fatty acid synthase activity in the liver upon its phosphorylation by the insulin receptor. Because peroxisome proliferator-activated receptor α (PPARα) transcriptionally suppresses CEACAM1 expression, we herein examined whether high fat down-regulates CEACAM1 expression in a PPARα-dependent mechanism. By activating PPARα, the lipid-lowering drug fenofibrate reverses dyslipidemia and improves insulin sensitivity in type 2 diabetes in part by promoting fatty acid oxidation. Despite reducing glucose-stimulated insulin secretion, fenofibrate treatment does not result in insulin insufficiency. To examine whether this is mediated by a parallel decrease in CEACAM1-dependent hepatic insulin clearance pathways, we fed wild-type and Pparα−/− null mice a high fat diet supplemented with either fenofibrate or Wy14643, a selective PPARα agonist, and examined their effect on insulin metabolism and action. We demonstrated that the decrease in insulin secretion by fenofibrate and Wy14643 is accompanied by reduction in insulin clearance in wild-type but not Pparα−/− mice, thereby maintaining normoinsulinemia and insulin sensitivity despite continuous high fat intake. Intact insulin secretion in L-CC1 mice with protected hepatic insulin clearance and CEACAM1 levels provides in vivo evidence that insulin secretion responds to changes in insulin clearance to maintain physiologic insulin and glucose homeostasis. These results also emphasize the relevant role of hepatic insulin extraction in regulating insulin sensitivity. PMID:27662905

Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization during Chemical Clearance of Acid Reflux.

PubMed

Woodley, Frederick W; Moore-Clingenpeel, Melissa; Machado, Rodrigo Strehl; Nemastil, Christopher J; Jadcherla, Sudarshan R; Hayes, Don; Kopp, Benjamin T; Kaul, Ajay; Di Lorenzo, Carlo; Mousa, Hayat

2017-09-01

Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to <18 years) and 16 age-matched children without cystic fibrosis. Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis ( p =0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

Immune Mediators of Rotavirus Antigenemia Clearance in Mice ▿

PubMed Central

Marcelin, Glendie; Miller, Amber D.; Blutt, Sarah E.; Conner, Margaret E.

2011-01-01

The immunological mediators that clear rotavirus antigenemia or viremia remain undefined. Immunodeficient mice and antibody transfer were used to test whether lymphocytes or rotavirus-specific serum antibodies are essential for resolving antigenemia. Clearance of antigenemia required lymphocytes, but neither T nor B lymphocytes were absolutely required. Transfer of convalescent-phase or nonneutralizing rotavirus-specific serum antibodies to the systemic compartment of severe-combined-immunodeficient (SCID) mice temporarily suppressed the onset or level of chronic rotavirus antigenemia. Our findings provide the first report demonstrating that clearance of rotavirus antigenemia and possibly viremia are mediated by multiple effector lymphocyte subsets and serum antibodies. PMID:21593155

Effect of tip clearance on performance of small axial hydraulic turbine

NASA Technical Reports Server (NTRS)

Boynton, J. L.; Rohlik, H. E.

1976-01-01

The first two stages of a six stage liquid oxygen turbine were tested in water. One and two stage performance was determined for one shrouded and two unshrouded blade end configurations over ranges of clearance and blade-jet speed ratio. First stage, two stage, and second stage efficiencies are included as well as the effect of clearance on mass flow for two stage operation.

78 FR 76849 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

... Activities: Proposed Collection; Comment Request; Generic Clearance for the Collection of Qualitative... Request (ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery... proposed information collection activity provides a means to garner qualitative customer and stakeholder...

A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels.

PubMed

Khetarpal, Sumeet A; Zeng, Xuemei; Millar, John S; Vitali, Cecilia; Somasundara, Amritha Varshini Hanasoge; Zanoni, Paolo; Landro, James A; Barucci, Nicole; Zavadoski, William J; Sun, Zhiyuan; de Haard, Hans; Toth, Ildikó V; Peloso, Gina M; Natarajan, Pradeep; Cuchel, Marina; Lund-Katz, Sissel; Phillips, Michael C; Tall, Alan R; Kathiresan, Sekar; DaSilva-Jardine, Paul; Yates, Nathan A; Rader, Daniel J

2017-09-01

Recent large-scale genetic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipoprotein (TRL) clearance pathway that are protective against coronary heart disease (CHD), independently of LDL cholesterol (LDL-C) levels. Insight into the mechanisms of protection of these variants may facilitate the development of new therapies for lowering TRL levels. The gene APOC3 encodes apoC-III, a critical inhibitor of triglyceride (TG) lipolysis and remnant TRL clearance. Here we report a detailed interrogation of the mechanism of TRL lowering by the APOC3 Ala43Thr (A43T) variant, the only missense (rather than protein-truncating) variant in APOC3 reported to be TG lowering and protective against CHD. We found that both human APOC3 A43T heterozygotes and mice expressing human APOC3 A43T display markedly reduced circulating apoC-III levels. In mice, this reduction is due to impaired binding of A43T apoC-III to lipoproteins and accelerated renal catabolism of free apoC-III. Moreover, the reduced content of apoC-III in TRLs resulted in accelerated clearance of circulating TRLs. On the basis of this protective mechanism, we developed a monoclonal antibody targeting lipoprotein-bound human apoC-III that promotes circulating apoC-III clearance in mice expressing human APOC3 and enhances TRL catabolism in vivo. These data reveal the molecular mechanism by which a missense variant in APOC3 causes reduced circulating TG levels and, hence, protects from CHD. This protective mechanism has the potential to be exploited as a new therapeutic approach to reduce apoC-III levels and circulating TRL burden.

5 CFR 720.307 - Interagency report clearance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Interagency report clearance. 720.307 Section 720.307 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) AFFIRMATIVE EMPLOYMENT PROGRAMS Disabled Veterans Affirmative Action Program § 720.307...

Malaria parasites target the hepatocyte receptor EphA2 for successful host infection.

PubMed

Kaushansky, Alexis; Douglass, Alyse N; Arang, Nadia; Vigdorovich, Vladimir; Dambrauskas, Nicholas; Kain, Heather S; Austin, Laura S; Sather, D Noah; Kappe, Stefan H I

2015-11-27

The invasion of a suitable host hepatocyte by mosquito-transmitted Plasmodium sporozoites is an essential early step in successful malaria parasite infection. Yet precisely how sporozoites target their host cell and facilitate productive infection remains largely unknown. We found that the hepatocyte EphA2 receptor was critical for establishing a permissive intracellular replication compartment, the parasitophorous vacuole. Sporozoites productively infected hepatocytes with high EphA2 expression, and the deletion of EphA2 protected mice from liver infection. Lack of host EphA2 phenocopied the lack of the sporozoite proteins P52 and P36. Our data suggest that P36 engages EphA2, which is likely to be a key step in establishing the permissive replication compartment. Copyright © 2015, American Association for the Advancement of Science.

MTTE: an innovative strategy for the evaluation of targeted/exome enrichment efficiency

PubMed Central

Klonowska, Katarzyna; Handschuh, Luiza; Swiercz, Aleksandra; Figlerowicz, Marek; Kozlowski, Piotr

2016-01-01

Although currently available strategies for the preparation of exome-enriched libraries are well established, a final validation of the libraries in terms of exome enrichment efficiency prior to the sequencing step is of considerable importance. Here, we present a strategy for the evaluation of exome enrichment, i.e., the Multipoint Test for Targeted-enrichment Efficiency (MTTE), PCR-based approach utilizing multiplex ligation-dependent probe amplification with capillary electrophoresis separation. We used MTTE for the analysis of subsequent steps of the Illumina TruSeq Exome Enrichment procedure. The calculated values of enrichment-associated parameters (i.e., relative enrichment, relative clearance, overall clearance, and fold enrichment) and the comparison of MTTE results with the actual enrichment revealed the high reliability of our assay. Additionally, the MTTE assay enabled the determination of the sequence-associated features that may confer bias in the enrichment of different targets. Importantly, the MTTE is low cost method that can be easily adapted to the region of interest important for a particular project. Thus, the MTTE strategy is attractive for post-capture validation in a variety of targeted/exome enrichment NGS projects. PMID:27572310

MTTE: an innovative strategy for the evaluation of targeted/exome enrichment efficiency.

PubMed

Klonowska, Katarzyna; Handschuh, Luiza; Swiercz, Aleksandra; Figlerowicz, Marek; Kozlowski, Piotr

2016-10-11

Although currently available strategies for the preparation of exome-enriched libraries are well established, a final validation of the libraries in terms of exome enrichment efficiency prior to the sequencing step is of considerable importance. Here, we present a strategy for the evaluation of exome enrichment, i.e., the Multipoint Test for Targeted-enrichment Efficiency (MTTE), PCR-based approach utilizing multiplex ligation-dependent probe amplification with capillary electrophoresis separation. We used MTTE for the analysis of subsequent steps of the Illumina TruSeq Exome Enrichment procedure. The calculated values of enrichment-associated parameters (i.e., relative enrichment, relative clearance, overall clearance, and fold enrichment) and the comparison of MTTE results with the actual enrichment revealed the high reliability of our assay. Additionally, the MTTE assay enabled the determination of the sequence-associated features that may confer bias in the enrichment of different targets. Importantly, the MTTE is low cost method that can be easily adapted to the region of interest important for a particular project. Thus, the MTTE strategy is attractive for post-capture validation in a variety of targeted/exome enrichment NGS projects.

76 FR 35069 - Agency Information Collection Activities; Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

... precision requirements or power calculations that justify the proposed sample size, the expected response...; Proposed Collection; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on... (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery...

76 FR 20714 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

... Activities: Proposed Collection; Comment Request; Generic Clearance for the Collection of Qualitative... Collection of Qualitative Feedback on Agency Service Delivery'' to OMB for approval under the Paperwork...: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery. Abstract...

78 FR 74175 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-10

... precision requirements or power calculations that justify the proposed sample size, the expected response...: Proposed Collection; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on... Information Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback...

76 FR 24920 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-03

... precision requirements or power calculations that justify the proposed sample size, the expected response... Collection; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service... Information Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback...

77 FR 52708 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

... calculations that justify the proposed sample size, the expected response rate, methods for assessing potential...: Proposed Collection; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on... Information Collection request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback...

76 FR 45573 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-29

... Technology Research Center survey. Abstract: The information collection activity will garner qualitative.... This type of generic clearance for qualitative information will not be used for quantitative... Collection; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service...

Turbine Engine Clearance Control Systems: Current Practices and Future Directions

NASA Astrophysics Data System (ADS)

Lattime, Scott B.; Steinetz, Bruce M.

2002-09-01

Improved blade tip sealing in the high pressure compressor (HPC) and high pressure turbine (HPT) can provide dramatic reductions in specific fuel consumption (SFC), time-on-wing, compressor stall margin, and engine efficiency as well as increased payload and mission range capabilities. Maintenance costs to overhaul large commercial gas turbine engines can easily exceed 1M. Engine removal from service is primarily due to spent exhaust gas temperature (EGT) margin caused mainly by the deterioration of HPT components. Increased blade tip clearance is a major factor in hot section component degradation. As engine designs continue to push the performance envelope with fewer parts and the market drives manufacturers to increase service life, the need for advanced sealing continues to grow. A review of aero gas turbine engine HPT performance degradation and the mechanisms that promote these losses are discussed. Benefits to the HPT due to improved clearance management are identified. Past and present sealing technologies are presented along with specifications for next generation engine clearance control systems.

Differentially regulated gene expression associated with hepatitis C virus clearance.

PubMed

Grimes, Carolyn Z; Hwang, Lu-Yu; Wei, Peng; Shah, Dimpy P; Volcik, Kelly A; Brown, Eric L

2013-03-01

Human chronic hepatitis C virus (HCV) infections pose a significant public health threat, necessitating the development of novel treatments and vaccines. HCV infections range from spontaneous resolution to end-stage liver disease. Approximately 10-30% of HCV infections undergo spontaneous resolution independent of treatment by yet-to-be-defined mechanisms. These individuals test positive for anti-HCV antibodies in the absence of detectable viral serum RNA. To identify genes associated with HCV clearance, this study compared gene expression profiles between current drug users chronically infected with HCV and drug users who cleared their HCV infection. This analysis identified 91 differentially regulated (up- or downregulated by twofold or more) genes potentially associated with HCV clearance. The majority of genes identified were associated with immune function, with the remaining genes categorized either as cancer related or 'other'. Identification of factors and pathways that may influence virus clearance will be essential to the development of novel treatment strategies.

Turbine Engine Clearance Control Systems: Current Practices and Future Directions

NASA Technical Reports Server (NTRS)

Lattime, Scott B.; Steinetz, Bruce M.

2002-01-01

Improved blade tip sealing in the high pressure compressor (HPC) and high pressure turbine (HPT) can provide dramatic reductions in specific fuel consumption (SFC), time-on-wing, compressor stall margin, and engine efficiency as well as increased payload and mission range capabilities. Maintenance costs to overhaul large commercial gas turbine engines can easily exceed $1M. Engine removal from service is primarily due to spent exhaust gas temperature (EGT) margin caused mainly by the deterioration of HPT components. Increased blade tip clearance is a major factor in hot section component degradation. As engine designs continue to push the performance envelope with fewer parts and the market drives manufacturers to increase service life, the need for advanced sealing continues to grow. A review of aero gas turbine engine HPT performance degradation and the mechanisms that promote these losses are discussed. Benefits to the HPT due to improved clearance management are identified. Past and present sealing technologies are presented along with specifications for next generation engine clearance control systems.

The effects of selected air pollutants on clearance of titanic oxide particles from the lungs of rats.

PubMed

Ferin, J; Leach, L J

1975-09-01

A procedure utilizing the lung clearance kinetics of titanic oxide (TiO2) particles was used to determine the effects of inhaled sulphur dioxide (SO2) and nitrogen oxides (NO x) on particle clearance. The procedure is reproducible and mainly tests clearance mechanisms involving alveolar macrophages and the mucociliary transport system at the alveolobronchial clearance pathway. At low SO2 or NOx exposures enhanced particle clearance was observed. Lung clearance was depressed at 15 and 24 ppm of NO2 after 22 exposures as well as at 20 ppm of SO2 after 11 exposures, and also at 1 ppm of SO2 after 25 exposures. Dose-response curves for the SO2 and NOx exposures showed differences explainable by the routes by which these gases reach the alveolar macrophages.

Repeated swim impairs serotonin clearance via a corticosterone-sensitive mechanism: organic cation transporter 3, the smoking gun.

PubMed

Baganz, Nicole; Horton, Rebecca; Martin, Kathryn; Holmes, Andrew; Daws, Lynette C

2010-11-10

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with increased extracellular serotonin (5-HT) in limbic brain regions. The mechanism through which this occurs remains unclear. One way could be via HPA axis-dependent impairment of serotonin transporter (SERT) function, the high-affinity uptake mechanism for 5-HT. Consistent with this idea, we found that 5-HT clearance rate in hippocampus was dramatically reduced in mice exposed to repeated swim, a stimulus known to activate the HPA axis. However, this phenomenon also occurred in mice lacking SERT, ruling out SERT as a mechanism. The organic cation transporter 3 (OCT3) is emerging as an important regulator of brain 5-HT. Moreover, corticosterone, which is released upon HPA axis activation, blocks 5-HT uptake by OCT3. Repeated swim produced a persistent elevation in plasma corticosterone, and, consistent with prolonged blockade by corticosterone, we found that OCT3 expression and function were reduced in these mice. Importantly, this effect of repeated swim to reduce 5-HT clearance rate was corticosterone dependent, as evidenced by its absence in adrenalectomized mice, in which plasma corticosterone levels were essentially undetectable. Behaviorally, mice subjected to repeated swim spent less time immobile in the tail suspension test than control mice, but responded similarly to SERT- and norepinephrine transporter-selective antidepressants. Together, these results show that reduced 5-HT clearance following HPA axis activation is likely mediated, at least in part, by the corticosterone-sensitive OCT3, and that drugs developed to selectively target OCT3 (unlike corticosterone) may be candidates for the development of novel antidepressant medications.

Effects of Speed and Visual-Target Distance on Toe Trajectory During the Swing Phase of Treadmill Walking

NASA Technical Reports Server (NTRS)

Miller, Christopher A.; Feiveson, Al; Bloomberg, Jacob J.

2007-01-01

Toe trajectory during swing phase is a precise motor control task that can provide insights into the sensorimotor control of the legs. The purpose of this study was to determine changes in vertical toe trajectory during treadmill walking due to changes in walking speed and target distance. For each trial, subjects walked on a treadmill at one of five speeds while performing a dynamic visual acuity task at either a far or near target distance (five speeds two targets distances = ten trials). Toe clearance decreased with increasing speed, and the vertical toe peak just before heel strike increased with increasing speed, regardless of target distance. The vertical toe peak just after toe-off was lower during near-target visual acuity tasks than during far-target tasks, but was not affected by speed. The ankle of the swing leg appeared to be the main joint angle that significantly affected all three toe trajectory events. The foot angle of the swing leg significantly affected toe clearance and the toe peak just before heel strike. These results will be used to enhance the analysis of lower limb kinematics during the sensorimotor treadmill testing, where differing speeds and/or visual target distances may be used.

Synthetic lipoprotein as nano-material vehicle in the targeted drug delivery.

PubMed

Zhang, Xueqin; Huang, Gangliang

2017-12-01

High-density lipoprotein (HDL) and low-density lipoprotein (LDL), as human endogenous lipoprotein particles, have low toxicity, high selectivity, and good safety. They can avoid the recognition and clearance of human reticuloendothelial system. These synthetic lipoproteins (sLPs) have been attracted extensive attention as the nanovectors for tumor-targeted drug and gene delivery. Herein, recent advances in the field of anticancer based on these two lipid proteins and recombinant lipoproteins (rLPs) as target delivery vectors were analyzed and discussed.

Tear clearance and ocular symptoms in patients treated with preservative-free prostaglandins.

PubMed

Giménez-Gómez, R; García-Catalán, M R; Gallardo-Galera, J M

2013-03-01

To assess the effects on dry eye symptoms and tear dynamics of switching from a prostaglandin with a preservative to a preservative-free prostaglandin. Fourteen patients (N=28 eyes) with open-angle glaucoma and dry eye symptons, treated with preserved latanoprost, travoprost or bimatoprost were included in this uncontrolled prospective study. Ocular symptoms were analysed using a validated ocular surface disease questionnaire and ocular signs were assessed with tear clearance, Schirmer and tear function index test (TFI=Schirmer/clearance). Patients were assigned to preservative-free tafluprost treatment, and measurements were repeated 4 weeks after change of medication. Wilcoxon test and Spearman correlation coefficient were used in the statistical analysis. No statistically significant difference in intraocular pressure (IOP) was observed after switching to tafluprost. Mean IOP at baseline was 20.4 mmHg (SD2.2) and after 4 weeks 19.9 mmHg (SD2.6), (P>.05). The mean questionnaire score significantly decreased from 9.7 (SD3.7) at baseline to 5.4 (SD2.7) after one month (P<.001). No significant differences in tear clearance, Schirmer or TFI were found (P>.05). At baseline, tear clearance=0.13 (SD0.07), Schirmer=10.7 mm (SD6) and TFI=80 (48-156). After 4 weeks, tear clearance=0.1(SD0.07), Schirmer=9.5 mm (3.9) and TFI=104 (48-216). A significant association between questionnaire score and tear clearance after 4 weeks was observed (Spearman coefficient=0.62; P=.014). Switching from preservative prostaglandin with a preservative to preservative-free tafluprost treatment improves dry eye symptoms and suggests an improvement in TFI. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

10 CFR 706.13 - Clearance of counsel.

Code of Federal Regulations, 2012 CFR

2012-01-01

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10 CFR 706.13 - Clearance of counsel.

Code of Federal Regulations, 2010 CFR

2010-01-01

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10 CFR 706.13 - Clearance of counsel.

Code of Federal Regulations, 2013 CFR

2013-01-01

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10 CFR 706.13 - Clearance of counsel.

Code of Federal Regulations, 2011 CFR

2011-01-01

... DEPARTMENT OF ENERGY SECURITY POLICIES AND PRACTICES RELATING TO LABOR-MANAGEMENT RELATIONS Security Policies... even though the record is to be unclassified. Clearance of counsel makes possible their participation in any closed discussions needed preparatory to making an unclassified record. Each party is...

10 CFR 706.13 - Clearance of counsel.

Code of Federal Regulations, 2014 CFR

2014-01-01

... DEPARTMENT OF ENERGY SECURITY POLICIES AND PRACTICES RELATING TO LABOR-MANAGEMENT RELATIONS Security Policies... even though the record is to be unclassified. Clearance of counsel makes possible their participation in any closed discussions needed preparatory to making an unclassified record. Each party is...

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CF6 jet engine diagnostics program. High pressure turbine roundness/clearance investigation

NASA Technical Reports Server (NTRS)

Howard, W. D.; Fasching, W. A.

1982-01-01

The effects of high pressure turbine clearance changes on engine and module performance was evaluated in addition to the measurement of CF6-50C high pressure turbine Stage 1 tip clearance and stator out-of-roundness during steady-state and transient operation. The results indicated a good correlation of the analytical model of round engine clearance response with measured data. The stator out-of-roundness measurements verified that the analytical technique for predicting the distortion effects of mechanical loads is accurate, whereas the technique for calculating the effects of certain circumferential thermal gradients requires some modifications. A potential for improvement in roundness was established in the order of 0.38 mm (0.015 in.), equivalent to 0.86 percent turbine efficiency which translates to a cruise SFC improvement of 0.36 percent. The HP turbine Stage 1 tip clearance performance derivative was established as 0.44 mm (17 mils) per percent of turbine efficiency at take-off power, somewhat smaller, therefore, more sensitive than predicted from previous investigations.

Rotor tip clearance effects on overall and blade-element performance of axial-flow transonic fan stage

NASA Technical Reports Server (NTRS)

Moore, R. D.

1982-01-01

The effects of tip clearance on the overall and blade-element performance of an axial-flow transonic fan stage are presented. The 50-centimeter-diameter fan was tested at four tip clearances (nonrotating) from 0.061 to 0.178 centimeter. The calculated radial growth of the blades was 0.040 centimeter at design conditions. The decrease in overall stage performance with increasing clearance is attributed to the loss in rotor performance. For the rotor the effects of clearance on performance parameters extended to about 70 percent of blade span from the tip. The stage still margin based on an assumed operating line decreased from 15.3 to 0 percent as the clearance increased from 0.061 to 0.178 centimeter.

Turbine blade tip clearance measurement using a skewed dual-beam fiber optic sensor

NASA Astrophysics Data System (ADS)

Ye, De-chao; Duan, Fa-jie; Guo, Hao-tian; Li, Yangzong; Wang, Kai

2012-08-01

Optimization and active control of the tip clearance of turbine blades has been identified as a key to improve fuel efficiency, reduce emission, and increase service life of the engine. However, reliable and real-time tip clearance measurement is difficult due to the adverse environmental conditions that are typically found in a turbine. We describe a dual-beam fiber optic measurement system that can measure the tip timing and tip clearance simultaneously. Because the tip timing information is used to calculate the tip clearance, the method is insensitive to the signal intensity variation caused by fluctuations in environmental conditions such as light source instability, contamination, and blade tip imperfection. The system was calibrated and tested using experimental rotors. The test results indicated a high resolution of 4.5 μm and measurement accuracy of ±20 μm over the rotation speed range of 2000 to 10,000 rpm.

Dual roles for hepatic lectin receptors in the clearance of chilled platelets

PubMed Central

Rumjantseva, Viktoria; Grewal, Prabhjit K.; Wandall, Hans H.; Josefsson, Emma C.; Sørensen, Anne Louise; Larson, Göran; Marth, Jamey D.; Hartwig, John H.; Hoffmeister, Karin M.

2015-01-01

Chilling rapidly (<4 h) clusters Glycoprotein - (GP)Ib receptors on blood platelets, and ß2-integrins of hepatic macrophages bind ßGlcNAc residues in the clusters leading to rapid clearance of acutely chilled platelets following transfusion. Although capping the ßGlcNAc moieties by galactosylation prevents clearance, this strategy is ineffective after prolonged (>24 h) refrigeration. We report here that prolonged refrigeration increases the density/concentration of exposed galactose residues such that hepatocytes become increasingly involved in the removal of platelets using their Ashwell-Morell receptors. Macrophages always rapidly remove a large fraction of transfused platelets (~40%). With platelet cooling, hepatocyte-dependent clearance further diminishes their recoveries following transfusion. PMID:19783995

Development of a Novel System to Measure a Clearance of a Passenger Platform

NASA Astrophysics Data System (ADS)

Shimizu, M.; Oizumi, J.; Matsuoka, R.; Takeda, H.; Okukura, H.; Ooya, A.; Koike, A.

2016-06-01

Clearances of a passenger platform at a railway station should be appropriately maintained for safety of both trains and passengers. In most Japanese railways clearances between a platform and a train car is measured precisely once or twice a year. Because current measurement systems operate on a track, the closure of the track is unavoidable. Since the procedure of the closure of a track is time-consuming and bothersome, we decided to develop a new system to measure clearances without the closure of a track. A new system is required to work on a platform and the required measurement accuracy is less than several millimetres. We have adopted a 3D laser scanner and stop-and-go operation for a new system. The current systems on a track measure clearances continuously at walking speed, while our system on a platform measures clearances at approximately ten metres intervals. The scanner controlled by a PC acquires a set of point data at each measuring station. Edge points of the platform, top and side points of two rails are detected from the acquired point data. Finally clearances of the platform are calculated by using the detected feature points of the platform and the rails. The results of an experiment using a prototype of our system show that the measurement accuracy by our system would be satisfactory, but our system would take more time than the current systems. Since our system requires no closure of a track, we conclude that our system would be convenient and effective.

Histaminergic regulation of natural killer cell-mediated clearance of tumour cells in mice.

PubMed

Asea, A; Hermodsson, S; Hellstrand, K

1996-01-01

Treatment of Swiss albino mice with histamine enhanced the clearance of natural killer (NK)-cell sensitive YAC-1 lymphoma and B16/F10 melanoma cells from lung tissue in vivo, but did not affect the elimination of NK-cell-insensitive P815 mastocytoma cells. The effect of histamine was apparently mediated by H2-type histamine receptors (H2R) since it was blocked by ranitidine, and H2R antagonist. Histamine did not affect clearance of tumour cells in animals depleted of NK cells in vivo by treatment with antibodies to asialo-GM1 or NK1.1. The effect of histamine was time-dependent: pretreatment with histamine for 3 h significantly augmented the clearance of YAC-1 cells, whereas, pretreatment with histamine for 5 min was ineffective. Histamine potentiated the anti-tumour properties of NK-cell activators such as interleukin-2 (IL-2) or interferon-alpha (IFN-alpha) in vivo. None of these lymphokines significantly affected the clearance of YAC-1 cells unless animals were concomitantly treated with histamine. Treatment with ranitidine alone reduced the in vivo clearance of YAC-1 cells from lungs but did not affect the clearance of NK-cell-insensitive P815 cells. Effects of ranitidine on NK-cell function in vivo were not shared by a chemical control to ranitidine, AH20239AA, thus indicating that the inhibition of NK-cells results from H2R antagonism rather than non-specific toxicity. It is concluded that histaminergic mechanisms may be involved in the regulation of NK cell function in vivo.

Physiological and Microfluorometric Studies of Reduction and Clearance of Retinal in Bleached Rod Photoreceptors

PubMed Central

Tsina, Efthymia; Chen, Chunhe; Koutalos, Yiannis; Ala-Laurila, Petri; Tsacopoulos, Marco; Wiggert, Barbara; Crouch, Rosalie K.; Cornwall, M. Carter

2004-01-01

The visual cycle comprises a sequence of reactions that regenerate the visual pigment in photoreceptors during dark adaptation, starting with the reduction of all-trans retinal to all-trans retinol and its clearance from photoreceptors. We have followed the reduction of retinal and clearance of retinol within bleached outer segments of red rods isolated from salamander retina by measuring its intrinsic fluorescence. Following exposure to a bright light (bleach), increasing fluorescence intensity was observed to propagate along the outer segments in a direction from the proximal region adjacent to the inner segment toward the distal tip. Peak retinol fluorescence was achieved after ∼30 min, after which it declined very slowly. Clearance of retinol fluorescence is considerably accelerated by the presence of the exogenous lipophilic substances IRBP (interphotoreceptor retinoid binding protein) and serum albumin. We have used simultaneous fluorometric and electrophysiological measurements to compare the rate of reduction of all-trans retinal to all-trans retinol to the rate of recovery of flash response amplitude in these cells in the presence and absence of IRBP. We find that flash response recovery in rods is modestly accelerated in the presence of extracellular IRBP. These results suggest such substances may participate in the clearance of retinoids from rod photoreceptors, and that this clearance, at least in rods, may facilitate dark adaptation by accelerating the clearance of photoproducts of bleaching. PMID:15452202

Methodological uncertainty in quantitative prediction of human hepatic clearance from in vitro experimental systems.

PubMed

Hallifax, D; Houston, J B

2009-03-01

Mechanistic prediction of unbound drug clearance from human hepatic microsomes and hepatocytes correlates with in vivo clearance but is both systematically low (10 - 20 % of in vivo clearance) and highly variable, based on detailed assessments of published studies. Metabolic capacity (Vmax) of commercially available human hepatic microsomes and cryopreserved hepatocytes is log-normally distributed within wide (30 - 150-fold) ranges; Km is also log-normally distributed and effectively independent of Vmax, implying considerable variability in intrinsic clearance. Despite wide overlap, average capacity is 2 - 20-fold (dependent on P450 enzyme) greater in microsomes than hepatocytes, when both are normalised (scaled to whole liver). The in vitro ranges contrast with relatively narrow ranges of clearance among clinical studies. The high in vitro variation probably reflects unresolved phenotypical variability among liver donors and practicalities in processing of human liver into in vitro systems. A significant contribution from the latter is supported by evidence of low reproducibility (several fold) of activity in cryopreserved hepatocytes and microsomes prepared from the same cells, between separate occasions of thawing of cells from the same liver. The large uncertainty which exists in human hepatic in vitro systems appears to dominate the overall uncertainty of in vitro-in vivo extrapolation, including uncertainties within scaling, modelling and drug dependent effects. As such, any notion of quantitative prediction of clearance appears severely challenged.

Osmotic diuresis-induced hypernatremia: better explained by solute-free water clearance or electrolyte-free water clearance?

PubMed

Popli, Subhash; Tzamaloukas, Antonios H; Ing, Todd S

2014-01-01

Hypernatremia may result from inadequate water intake, excessive water loss or a combination of the two. Osmotic diuresis leads to losses of both solute and water. The relationship between solute and water losses determines the resulting changes in serum osmolality and sodium concentration. Total solute loss is routinely higher than loss of water in osmotic diuresis. Theoretically, then, decreases in serum osmolality (and serum sodium concentration) should follow. In clinical situations of osmotic diuresis, however, reduction in osmolality can take place, but not reduction in serum sodium concentration. It is of note that serum sodium concentration changes are related to urinary losses of sodium and potassium but not to the loss of total solute. In osmotic diuresis, the combined loss of sodium and potassium per liter of urine is lower than the concurrent serum sodium level. Consequently, hypernatremia can ensue. A patient who presented with osmotic diuresis and hypernatremia is described here. In this patient, we have shown that electrolyte-free water clearance is a better index of the effect of osmotic diuresis on serum sodium concentration than the classic solute-free water clearance.

High Temperature Investigations into an Active Turbine Blade Tip Clearance Control Concept

NASA Technical Reports Server (NTRS)

Taylor, Shawn; Steinetz, Bruce M.; Oswald, Jay J.

2007-01-01

System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA s Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

High Temperature Investigations into an Active Turbine Blade Tip Clearance Control Concept

NASA Technical Reports Server (NTRS)

Taylor, Shawn C.; Steinetz, Bruce; Oswald, Jay J.

2008-01-01

System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA s Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

76 FR 14948 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

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Railway clearance intrusion detection method with binocular stereo vision

NASA Astrophysics Data System (ADS)

Zhou, Xingfang; Guo, Baoqing; Wei, Wei

2018-03-01

In the stage of railway construction and operation, objects intruding railway clearance greatly threaten the safety of railway operation. Real-time intrusion detection is of great importance. For the shortcomings of depth insensitive and shadow interference of single image method, an intrusion detection method with binocular stereo vision is proposed to reconstruct the 3D scene for locating the objects and judging clearance intrusion. The binocular cameras are calibrated with Zhang Zhengyou's method. In order to improve the 3D reconstruction speed, a suspicious region is firstly determined by background difference method of a single camera's image sequences. The image rectification, stereo matching and 3D reconstruction process are only executed when there is a suspicious region. A transformation matrix from Camera Coordinate System(CCS) to Track Coordinate System(TCS) is computed with gauge constant and used to transfer the 3D point clouds into the TCS, then the 3D point clouds are used to calculate the object position and intrusion in TCS. The experiments in railway scene show that the position precision is better than 10mm. It is an effective way for clearance intrusion detection and can satisfy the requirement of railway application.

The provision of clearances accuracy in piston - cylinder mating

NASA Astrophysics Data System (ADS)

Glukhov, V. I.; Shalay, V. V.

2017-08-01

The paper is aimed at increasing the quality of the pumping equipment in oil and gas industry. The main purpose of the study is to stabilize maximum values of productivity and durability of the pumping equipment based on the selective assembly of the cylinder-piston kinematic mating by optimization criterion. It is shown that the minimum clearance in the piston-cylinder mating is formed by maximum material dimensions. It is proved that maximum material dimensions are characterized by their own laws of distribution within the tolerance limits for the diameters of the cylinder internal mirror and the outer cylindrical surface of the piston. At that, their dispersion zones should be divided into size groups with a group tolerance equal to half the tolerance for the minimum clearance. The techniques for measuring the material dimensions - the smallest cylinder diameter and the largest piston diameter according to the envelope condition - are developed for sorting them into size groups. Reliable control of the dimensions precision ensures optimal minimum clearances of the piston-cylinder mating in all the size groups of the pumping equipment, necessary for increasing the equipment productivity and durability during the production, operation and repair processes.