Inline UV/Vis spectroscopy as PAT tool for hot-melt extrusion.

PubMed

Wesholowski, Jens; Prill, Sebastian; Berghaus, Andreas; Thommes, Markus

2018-01-11

Hot-melt extrusion on co-rotating twin screw extruders is a focused technology for the production of pharmaceuticals in the context of Quality by Design. Since it is a continuous process, the potential for minimizing product quality fluctuation is enhanced. A typical application of hot-melt extrusion is the production of solid dispersions, where an active pharmaceutical ingredient (API) is distributed within a polymer matrix carrier. For this dosage form, the product quality is related amongst others to the drug content. This can be monitored on- or inline as critical quality attribute by a process analytical technology (PAT) in order to meet the specific requirements of Quality by Design. In this study, an inline UV/Vis spectrometer from ColVisTec was implemented in an early development twin screw extruder and the performance tested in accordance to the ICH Q2 guideline. Therefore, two API (carbamazepine and theophylline) and one polymer matrix (copovidone) were considered with the main focus on the quantification of the drug load. The obtained results revealed the suitability of the implemented PAT tool to quantify the drug load in a typical range for pharmaceutical applications. The effort for data evaluation was minimal due to univariate data analysis, and in combination with a measurement frequency of 1 Hz, the system is sufficient for real-time data acquisition.

National policy on physical activity: the development of a policy audit tool.

PubMed

Bull, Fiona C; Milton, Karen; Kahlmeier, Sonja

2014-02-01

Physical inactivity is a leading risk factor for noncommunicable disease worldwide. Increasing physical activity requires large scale actions and relevant, supportive national policy across multiple sectors. The policy audit tool (PAT) was developed to provide a standardized instrument to assess national policy approaches to physical activity. A draft tool, based on earlier work, was developed and pilot-tested in 7 countries. After several rounds of revisions, the final PAT comprises 27 items and collects information on 1) government structure, 2) development and content of identified key policies across multiple sectors, 3) the experience of policy implementation at both the national and local level, and 4) a summary of the PAT completion process. PAT provides a standardized instrument for assessing progress of national policy on physical activity. Engaging a diverse international group of countries in the development helped ensure PAT has applicability across a wide range of countries and contexts. Experiences from the development of the PAT suggests that undertaking an audit of health enhancing physical activity (HEPA) policy can stimulate greater awareness of current policy opportunities and gaps, promote critical debate across sectors, and provide a catalyst for collaboration on policy level actions. The final tool is available online.

Aerospace Technologies of the 21st Century: New Technologies of Experimental Research and Simulation Held in Berlin, Germany on 8-9 June 2000

DTIC Science & Technology

2000-01-01

11. Gal-Or, B., U.S. PAT. Appl .. 08/516870/1, Aug. 18, 1995 & Isr. Pat. Appl . 113636, May 7,1995 by Gal- Or, Lichtsinder and Sherbaum.. 12. Gal-Or...B., U.S. PAT. Appl . 08/516870/2, Aug. 18, 1995 & Isr. Pat. Appl . 111265, Oct. 12,94 by Gal- Or, Lichtsinder and Sherbaum. 13. Gal-Or, B., U.S. PAT... Appl . 08/554087, Nov. 6,1995. 14. Gal-Or, B., ?Proposed Flight Testing Standards for Engine Thrust Vectoring to Maximize Kill Ra- tios, Post-Stall

Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing.

PubMed

Esmonde-White, Karen A; Cuellar, Maryann; Uerpmann, Carsten; Lenain, Bruno; Lewis, Ian R

2017-01-01

Adoption of Quality by Design (QbD) principles, regulatory support of QbD, process analytical technology (PAT), and continuous manufacturing are major factors effecting new approaches to pharmaceutical manufacturing and bioprocessing. In this review, we highlight new technology developments, data analysis models, and applications of Raman spectroscopy, which have expanded the scope of Raman spectroscopy as a process analytical technology. Emerging technologies such as transmission and enhanced reflection Raman, and new approaches to using available technologies, expand the scope of Raman spectroscopy in pharmaceutical manufacturing, and now Raman spectroscopy is successfully integrated into real-time release testing, continuous manufacturing, and statistical process control. Since the last major review of Raman as a pharmaceutical PAT in 2010, many new Raman applications in bioprocessing have emerged. Exciting reports of in situ Raman spectroscopy in bioprocesses complement a growing scientific field of biological and biomedical Raman spectroscopy. Raman spectroscopy has made a positive impact as a process analytical and control tool for pharmaceutical manufacturing and bioprocessing, with demonstrated scientific and financial benefits throughout a product's lifecycle.

An Application of X-Ray Fluorescence as Process Analytical Technology (PAT) to Monitor Particle Coating Processes.

PubMed

Nakano, Yoshio; Katakuse, Yoshimitsu; Azechi, Yasutaka

2018-06-01

An attempt to apply X-Ray Fluorescence (XRF) analysis to evaluate small particle coating process as a Process Analytical Technologies (PAT) was made. The XRF analysis was used to monitor coating level in small particle coating process with at-line manner. The small particle coating process usually consists of multiple coating processes. This study was conducted by a simple coating particles prepared by first coating of a model compound (DL-methionine) and second coating by talc on spherical microcrystalline cellulose cores. The particles with two layered coating are enough to demonstrate the small particle coating process. From the result by the small particle coating process, it was found that the XRF signal played different roles, resulting that XRF signals by first coating (layering) and second coating (mask coating) could demonstrate the extent with different mechanisms for the coating process. Furthermore, the particle coating of the different particle size has also been investigated to evaluate size effect of these coating processes. From these results, it was concluded that the XRF could be used as a PAT in monitoring particle coating processes and become powerful tool in pharmaceutical manufacturing.

Methodology Development for Assessment of Spaceport Technology Returns and Risks

NASA Technical Reports Server (NTRS)

Joglekar, Prafulla; Zapata, Edgar

2001-01-01

As part of Kennedy Space Center's (KSC's) challenge to open the space frontier, new spaceport technologies must be developed, matured and successfully transitioned to operational systems. R&D investment decisions can be considered from multiple perspectives. Near mid and far term technology horizons must be understood. Because a multitude of technology investment opportunities are available, we must identify choices that promise the greatest likelihood of significant lifecycle At the same time, the costs and risks of any choice must be well understood and balanced against its potential returns The problem is not one of simply rank- ordering projects in terms of their desirability. KSC wants to determine a portfolio of projects that simultaneously satisfies multiple goals, such as getting the biggest bang for the buck, supporting projects that may be too risky for private funding, staying within annual budget cycles without foregoing the requirements of a long term technology vision, and ensuring the development of a diversity of technologies that, support the variety of operational functions involved in space transportation. This work aims to assist in the development of in methods and techniques that support strategic technology investment decisions and ease the process of determining an optimal portfolio of spaceport R&D investments. Available literature on risks and returns to R&D is reviewed and most useful pieces are brought to the attention of the Spaceport Technology Development Office (STDO). KSC's current project management procedures are reviewed. It is found that the "one size fits all" nature of KSC's existing procedures and project selection criteria is not conducive to prudent decision-making. Directions for improving KSC's - procedures and criteria are outlined. With help of a contractor, STDO is currently developing a tool, named Change Management Analysis Tool (CMAT)/ Portfolio Analysis Tool (PAT), to assist KSC's R&D portfolio determination. A critical review of CMAT/PAT is undertaken. Directions for the improvement of this tool are provided. STDO and KSC intend to follow up on many, if not all, of the recommendations provided.

Near-infrared spectroscopy monitoring and control of the fluidized bed granulation and coating processes-A review.

PubMed

Liu, Ronghua; Li, Lian; Yin, Wenping; Xu, Dongbo; Zang, Hengchang

2017-09-15

The fluidized bed granulation and pellets coating technologies are widely used in pharmaceutical industry, because the particles made in a fluidized bed have good flowability, compressibility, and the coating thickness of pellets are homogeneous. With the popularization of process analytical technology (PAT), real-time analysis for critical quality attributes (CQA) was getting more attention. Near-infrared (NIR) spectroscopy, as a PAT tool, could realize the real-time monitoring and control during the granulating and coating processes, which could optimize the manufacturing processes. This article reviewed the application of NIR spectroscopy in CQA (moisture content, particle size and tablet/pellet thickness) monitoring during fluidized bed granulation and coating processes. Through this review, we would like to provide references for realizing automated control and intelligent production in fluidized bed granulation and pellets coating of pharmaceutical industry. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential of Near-Infrared Chemical Imaging as Process Analytical Technology Tool for Continuous Freeze-Drying.

PubMed

Brouckaert, Davinia; De Meyer, Laurens; Vanbillemont, Brecht; Van Bockstal, Pieter-Jan; Lammens, Joris; Mortier, Séverine; Corver, Jos; Vervaet, Chris; Nopens, Ingmar; De Beer, Thomas

2018-04-03

Near-infrared chemical imaging (NIR-CI) is an emerging tool for process monitoring because it combines the chemical selectivity of vibrational spectroscopy with spatial information. Whereas traditional near-infrared spectroscopy is an attractive technique for water content determination and solid-state investigation of lyophilized products, chemical imaging opens up possibilities for assessing the homogeneity of these critical quality attributes (CQAs) throughout the entire product. In this contribution, we aim to evaluate NIR-CI as a process analytical technology (PAT) tool for at-line inspection of continuously freeze-dried pharmaceutical unit doses based on spin freezing. The chemical images of freeze-dried mannitol samples were resolved via multivariate curve resolution, allowing us to visualize the distribution of mannitol solid forms throughout the entire cake. Second, a mannitol-sucrose formulation was lyophilized with variable drying times for inducing changes in water content. Analyzing the corresponding chemical images via principal component analysis, vial-to-vial variations as well as within-vial inhomogeneity in water content could be detected. Furthermore, a partial least-squares regression model was constructed for quantifying the water content in each pixel of the chemical images. It was hence concluded that NIR-CI is inherently a most promising PAT tool for continuously monitoring freeze-dried samples. Although some practicalities are still to be solved, this analytical technique could be applied in-line for CQA evaluation and for detecting the drying end point.

Direct analysis in real time mass spectrometry, a process analytical technology tool for real-time process monitoring in botanical drug manufacturing.

PubMed

Wang, Lu; Zeng, Shanshan; Chen, Teng; Qu, Haibin

2014-03-01

A promising process analytical technology (PAT) tool has been introduced for batch processes monitoring. Direct analysis in real time mass spectrometry (DART-MS), a means of rapid fingerprint analysis, was applied to a percolation process with multi-constituent substances for an anti-cancer botanical preparation. Fifteen batches were carried out, including ten normal operations and five abnormal batches with artificial variations. The obtained multivariate data were analyzed by a multi-way partial least squares (MPLS) model. Control trajectories were derived from eight normal batches, and the qualification was tested by R(2) and Q(2). Accuracy and diagnosis capability of the batch model were then validated by the remaining batches. Assisted with high performance liquid chromatography (HPLC) determination, process faults were explained by corresponding variable contributions. Furthermore, a batch level model was developed to compare and assess the model performance. The present study has demonstrated that DART-MS is very promising in process monitoring in botanical manufacturing. Compared with general PAT tools, DART-MS offers a particular account on effective compositions and can be potentially used to improve batch quality and process consistency of samples in complex matrices. Copyright © 2014 Elsevier B.V. All rights reserved.

Processing of baby food using pressure-assisted thermal sterilization (PATS) and comparison with thermal treatment

NASA Astrophysics Data System (ADS)

Wang, Yubin; Ismail, Marliya; Farid, Mohammed

2017-10-01

Currently baby food is sterilized using retort processing that gives an extended shelf life. However, this type of heat processing leads to reduction of organoleptic and nutrition value. Alternatively, the combination of pressure and heat could be used to achieve sterilization at reduced temperatures. This study investigates the potential of pressure-assisted thermal sterilization (PATS) technology for baby food sterilization. Here, baby food (apple puree), inoculated with Bacillus subtilis spores was treated using PATS at different operating temperatures, pressures and times and was compared with thermal only treatment. The results revealed that the decimal reduction time of B. subtilis in PATS treatment was lower than that of thermal only treatment. At a similar spore inactivation, the retention of ascorbic acid of PATS-treated sample was higher than that of thermally treated sample. The results indicated that PATS could be a potential technology for baby food processing while minimizing quality deterioration.

Noninvasive Spatially Offset and Transmission Raman Mapping of Breast Tissue: A Multimodal Approach toward the in Vivo Assessment of Tissue Pathology

DTIC Science & Technology

2012-04-01

in breast cancer clinical practice and research to independently develop a new technology from a concept. My learning objectives include the...o ........... ...,. of laur .........,. ~: (1) tluo .. ,.. data ..... at I(,,II,P), (1) the raw valu. ot tluo tam %. polnla 1(..,, v, Ill) OJUIJ...technology (PAT) tool for the in-line monitoring and understanding of a powder blending process. ]oumtd of Phannaceu.tical and Biumedical Antdysis, 48

Multi-scale Functional and Molecular Photoacoustic Tomography

PubMed Central

Yao, Junjie; Xia, Jun; Wang, Lihong V.

2015-01-01

Photoacoustic tomography (PAT) combines rich optical absorption contrast with the high spatial resolution of ultrasound at depths in tissue. The high scalability of PAT has enabled anatomical imaging of biological structures ranging from organelles to organs. The inherent functional and molecular imaging capabilities of PAT have further allowed it to measure important physiological parameters and track critical cellular activities. Integration of PAT with other imaging technologies provides complementary capabilities and can potentially accelerate the clinical translation of PAT. PMID:25933617

A quality by design study applied to an industrial pharmaceutical fluid bed granulation.

PubMed

Lourenço, Vera; Lochmann, Dirk; Reich, Gabriele; Menezes, José C; Herdling, Thorsten; Schewitz, Jens

2012-06-01

The pharmaceutical industry is encouraged within Quality by Design (QbD) to apply science-based manufacturing principles to assure quality not only of new but also of existing processes. This paper presents how QbD principles can be applied to an existing industrial pharmaceutical fluid bed granulation (FBG) process. A three-step approach is presented as follows: (1) implementation of Process Analytical Technology (PAT) monitoring tools at the industrial scale process, combined with multivariate data analysis (MVDA) of process and PAT data to increase the process knowledge; (2) execution of scaled-down designed experiments at a pilot scale, with adequate PAT monitoring tools, to investigate the process response to intended changes in Critical Process Parameters (CPPs); and finally (3) the definition of a process Design Space (DS) linking CPPs to Critical to Quality Attributes (CQAs), within which product quality is ensured by design, and after scale-up enabling its use at the industrial process scale. The proposed approach was developed for an existing industrial process. Through enhanced process knowledge established a significant reduction in product CQAs, variability already within quality specifications ranges was achieved by a better choice of CPPs values. The results of such step-wise development and implementation are described. Copyright © 2012 Elsevier B.V. All rights reserved.

Portfolio Analysis Tool

NASA Technical Reports Server (NTRS)

Barth, Tim; Zapata, Edgar; Benjamin, Perakath; Graul, Mike; Jones, Doug

2005-01-01

Portfolio Analysis Tool (PAT) is a Web-based, client/server computer program that helps managers of multiple projects funded by different customers to make decisions regarding investments in those projects. PAT facilitates analysis on a macroscopic level, without distraction by parochial concerns or tactical details of individual projects, so that managers decisions can reflect the broad strategy of their organization. PAT is accessible via almost any Web-browser software. Experts in specific projects can contribute to a broad database that managers can use in analyzing the costs and benefits of all projects, but do not have access for modifying criteria for analyzing projects: access for modifying criteria is limited to managers according to levels of administrative privilege. PAT affords flexibility for modifying criteria for particular "focus areas" so as to enable standardization of criteria among similar projects, thereby making it possible to improve assessments without need to rewrite computer code or to rehire experts, and thereby further reducing the cost of maintaining and upgrading computer code. Information in the PAT database and results of PAT analyses can be incorporated into a variety of ready-made or customizable tabular or graphical displays.

Patscanui: an intuitive web interface for searching patterns in DNA and protein data.

PubMed

Blin, Kai; Wohlleben, Wolfgang; Weber, Tilmann

2018-05-02

Patterns in biological sequences frequently signify interesting features in the underlying molecule. Many tools exist to search for well-known patterns. Less support is available for exploratory analysis, where no well-defined patterns are known yet. PatScanUI (https://patscan.secondarymetabolites.org/) provides a highly interactive web interface to the powerful generic pattern search tool PatScan. The complex PatScan-patterns are created in a drag-and-drop aware interface allowing researchers to do rapid prototyping of the often complicated patterns useful to identifying features of interest.

Logistics Process Analysis ToolProcess Analysis Tool

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

2008-03-31

LPAT is the resulting integrated system between ANL-developed Enhanced Logistics Intra Theater Support Tool (ELIST) sponsored by SDDC-TEA and the Fort Future Virtual Installation Tool (sponsored by CERL). The Fort Future Simulation Engine was an application written in the ANL Repast Simphony framework and used as the basis for the process Anlysis Tool (PAT) which evolved into a stand=-along tool for detailed process analysis at a location. Combined with ELIST, an inter-installation logistics component was added to enable users to define large logistical agent-based models without having to program. PAT is the evolution of an ANL-developed software system called Fortmore » Future Virtual Installation Tool (sponsored by CERL). The Fort Future Simulation Engine was an application written in the ANL Repast Simphony framework and used as the basis for the Process Analysis Tool(PAT) which evolved into a stand-alone tool for detailed process analysis at a location (sponsored by the SDDC-TEA).« less

Process analytical technologies (PAT) in freeze-drying of parenteral products.

PubMed

Patel, Sajal Manubhai; Pikal, Michael

2009-01-01

Quality by Design (QbD), aims at assuring quality by proper design and control, utilizing appropriate Process Analytical Technologies (PAT) to monitor critical process parameters during processing to ensure that the product meets the desired quality attributes. This review provides a comprehensive list of process monitoring devices that can be used to monitor critical process parameters and will focus on a critical review of the viability of the PAT schemes proposed. R&D needs in PAT for freeze-drying have also been addressed with particular emphasis on batch techniques that can be used on all the dryers independent of the dryer scale.

Biologically relevant photoacoustic imaging phantoms with tunable optical and acoustic properties

PubMed Central

Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Joshua Pfefer, T.

2016-01-01

Abstract. Established medical imaging technologies such as magnetic resonance imaging and computed tomography rely on well-validated tissue-simulating phantoms for standardized testing of device image quality. The availability of high-quality phantoms for optical-acoustic diagnostics such as photoacoustic tomography (PAT) will facilitate standardization and clinical translation of these emerging approaches. Materials used in prior PAT phantoms do not provide a suitable combination of long-term stability and realistic acoustic and optical properties. Therefore, we have investigated the use of custom polyvinyl chloride plastisol (PVCP) formulations for imaging phantoms and identified a dual-plasticizer approach that provides biologically relevant ranges of relevant properties. Speed of sound and acoustic attenuation were determined over a frequency range of 4 to 9 MHz and optical absorption and scattering over a wavelength range of 400 to 1100 nm. We present characterization of several PVCP formulations, including one designed to mimic breast tissue. This material is used to construct a phantom comprised of an array of cylindrical, hemoglobin-filled inclusions for evaluation of penetration depth. Measurements with a custom near-infrared PAT imager provide quantitative and qualitative comparisons of phantom and tissue images. Results indicate that our PVCP material is uniquely suitable for PAT system image quality evaluation and may provide a practical tool for device validation and intercomparison. PMID:26886681

Developing the Thai Siriraj Psoriatic Arthritis Screening Tool and validating the Thai Psoriasis Epidemiology Screening Tool and the Early Arthritis for Psoriatic Patients questionnaire.

PubMed

Chiowchanwisawakit, Praveena; Wattanamongkolsil, Luksame; Srinonprasert, Varalak; Petcharat, Chonachan; Siriwanarangsun, Palanan; Katchamart, Wanruchada

2016-10-01

To validate the Thai language version of the Psoriasis Epidemiology Screening Tool (PEST) and the Early Arthritis for Psoriatic Patients Questionnaire (EARP), as well as also to develop a new tool for screening psoriatic arthritis (PsA) among psoriasis (Ps) patients. This was a cross-sectional study. Ps patients visiting the psoriasis clinic at Siriraj Hospital were recruited. They completed the EARP and PEST. Full musculoskeletal history, examination, and radiography were evaluated. PsA was diagnosed by a rheumatologist's evaluation and fulfillment of the classification criteria for psoriatic arthritis. Receiver operator characteristic (ROC) curves, sensitivity, and specificity were used to evaluate the performances of the tools. The Siriraj Psoriatic Arthritis Screening Tool (SiPAT) contained questions most relevant to peripheral arthritis, axial inflammation, and enthesitis, selected from multivariate analysis. Of a total of 159 patients, the prevalence of PsA was 78.6 %. The ROC curve analyses of Thai EARP, PEST, and SiPAT were 0.90 (95 % CI 0.84, 0.96), 0.85 (0.78, 0.92), and 0.89 (0.83, 0.95), respectively. The sensitivities of SiPAT, Thai EARP, and PEST were 91.0, 83.0, and 72.0 %, respectively, while the specificities were 69.0, 79.3, and 89.7 %, respectively. All screening questionnaires showed good diagnostic performances. SiPAT could be considered as a screening tool with its desirable properties: higher sensitivity and taking less time. Thai PEST and EARP could possibly be sequentially administered for people with a positive test from SiPAT to reduce the number of false positives.

Contrast-enhanced photoacoustic tomography of human joints

NASA Astrophysics Data System (ADS)

Tian, Chao; Keswani, Rahul K.; Gandikota, Girish; Rosania, Gus R.; Wang, Xueding

2016-03-01

Photoacoustic tomography (PAT) provides a unique tool to diagnose inflammatory arthritis. However, the specificity and sensitivity of PAT based on endogenous contrasts is limited. The development of contrast enhanced PAT imaging modalities in combination with small molecule contrast agents could lead to improvements in diagnosis and treatment of joint disease. Accordingly, we adapted and tested a PAT clinical imaging system for imaging the human joints, in combination with a novel PAT contrast agent derived from an FDA-approved small molecule drug. Imaging results based on a photoacoustic and ultrasound (PA/US) dual-modality system revealed that this contrast-enhanced PAT imaging system may offer additional information beyond single-modality PA or US imaging system, for the imaging, diagnosis and assessment of inflammatory arthritis.

iPat: intelligent prediction and association tool for genomic research.

PubMed

Chen, Chunpeng James; Zhang, Zhiwu

2018-06-01

The ultimate goal of genomic research is to effectively predict phenotypes from genotypes so that medical management can improve human health and molecular breeding can increase agricultural production. Genomic prediction or selection (GS) plays a complementary role to genome-wide association studies (GWAS), which is the primary method to identify genes underlying phenotypes. Unfortunately, most computing tools cannot perform data analyses for both GWAS and GS. Furthermore, the majority of these tools are executed through a command-line interface (CLI), which requires programming skills. Non-programmers struggle to use them efficiently because of the steep learning curves and zero tolerance for data formats and mistakes when inputting keywords and parameters. To address these problems, this study developed a software package, named the Intelligent Prediction and Association Tool (iPat), with a user-friendly graphical user interface. With iPat, GWAS or GS can be performed using a pointing device to simply drag and/or click on graphical elements to specify input data files, choose input parameters and select analytical models. Models available to users include those implemented in third party CLI packages such as GAPIT, PLINK, FarmCPU, BLINK, rrBLUP and BGLR. Users can choose any data format and conduct analyses with any of these packages. File conversions are automatically conducted for specified input data and selected packages. A GWAS-assisted genomic prediction method was implemented to perform genomic prediction using any GWAS method such as FarmCPU. iPat was written in Java for adaptation to multiple operating systems including Windows, Mac and Linux. The iPat executable file, user manual, tutorials and example datasets are freely available at http://zzlab.net/iPat. zhiwu.zhang@wsu.edu.

In-line Fourier-transform infrared spectroscopy as a versatile process analytical technology for preparative protein chromatography.

PubMed

Großhans, Steffen; Rüdt, Matthias; Sanden, Adrian; Brestrich, Nina; Morgenstern, Josefine; Heissler, Stefan; Hubbuch, Jürgen

2018-04-27

Fourier-transform infrared spectroscopy (FTIR) is a well-established spectroscopic method in the analysis of small molecules and protein secondary structure. However, FTIR is not commonly applied for in-line monitoring of protein chromatography. Here, the potential of in-line FTIR as a process analytical technology (PAT) in downstream processing was investigated in three case studies addressing the limits of currently applied spectroscopic PAT methods. A first case study exploited the secondary structural differences of monoclonal antibodies (mAbs) and lysozyme to selectively quantify the two proteins with partial least squares regression (PLS) giving root mean square errors of cross validation (RMSECV) of 2.42 g/l and 1.67 g/l, respectively. The corresponding Q 2 values are 0.92 and, respectively, 0.99, indicating robust models in the calibration range. Second, a process separating lysozyme and PEGylated lysozyme species was monitored giving an estimate of the PEGylation degree of currently eluting species with RMSECV of 2.35 g/l for lysozyme and 1.24 g/l for PEG with Q 2 of 0.96 and 0.94, respectively. Finally, Triton X-100 was added to a feed of lysozyme as a typical process-related impurity. It was shown that the species could be selectively quantified from the FTIR 3D field without PLS calibration. In summary, the proposed PAT tool has the potential to be used as a versatile option for monitoring protein chromatography. It may help to achieve a more complete implementation of the PAT initiative by mitigating limitations of currently used techniques. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Non-Invasive Detection of Risk for Emotion Provoked Myocardial Ischemia

PubMed Central

Burg, Matthew M.; Graeber, Brendon; Vashist, Aseem; Collins, Dorothea; Earley, Christine; Liu, Joyce; Lampert, Rachel; Soufer, Robert

2009-01-01

Objectives To test an easily administered, noninvasive technology to identify vulnerability to mental stress ischemia. Background Myocardial ischemia provoked by emotional stress (MSI) in patients with stable coronary artery disease (CAD) predicts major adverse cardiac events. A clinically useful tool to risk stratify patients on this factor is not available. Methods Patients with documented CAD (n=68) underwent single photon emission computed tomography (SPECT) myocardial perfusion imaging concurrent with pulse wave amplitude assessment by peripheral arterial tonometry (PAT) during a mental stress protocol of sequential rest and anger stress periods. Heart rate and blood pressure were assessed, and blood was drawn for catecholamine assay, during rest and stress. MSI was defined by the presence of a new perfusion defect during anger stress (n=26) and the ratio of stress to rest PAT response was calculated. Results Patients with MSI had a significantly lower PAT ratio than those without MSI (0.76 ± 0.04 vs. 0.91 ± 0.05, p=0.03). An ROC curve for optimum sensitivity/specificity of PAT ratio as an index of MSI produced a sensitivity of 0.62 and a specificity of 0.63. Among patients taking angiotensin converter enzyme (ACE) inhibitors, the sensitivity and specificity of the test increased to 0.86 and 0.73 (respectively); 90% of patients without MSI were correctly identified. Conclusions PAT in concert with ACE inhibition may provide a useful approach to assess risk for MSI. Future studies should help determine how best to utilize this approach for risk assessment in the clinical setting. PMID:18941131

CMS Configuration Editor: GUI based application for user analysis job

NASA Astrophysics Data System (ADS)

de Cosa, A.

2011-12-01

We present the user interface and the software architecture of the Configuration Editor for the CMS experiment. The analysis workflow is organized in a modular way integrated within the CMS framework that organizes in a flexible way user analysis code. The Python scripting language is adopted to define the job configuration that drives the analysis workflow. It could be a challenging task for users, especially for newcomers, to develop analysis jobs managing the configuration of many required modules. For this reason a graphical tool has been conceived in order to edit and inspect configuration files. A set of common analysis tools defined in the CMS Physics Analysis Toolkit (PAT) can be steered and configured using the Config Editor. A user-defined analysis workflow can be produced starting from a standard configuration file, applying and configuring PAT tools according to the specific user requirements. CMS users can adopt this tool, the Config Editor, to create their analysis visualizing in real time which are the effects of their actions. They can visualize the structure of their configuration, look at the modules included in the workflow, inspect the dependences existing among the modules and check the data flow. They can visualize at which values parameters are set and change them according to what is required by their analysis task. The integration of common tools in the GUI needed to adopt an object-oriented structure in the Python definition of the PAT tools and the definition of a layer of abstraction from which all PAT tools inherit.

Combining microwave resonance technology to multivariate data analysis as a novel PAT tool to improve process understanding in fluid bed granulation.

PubMed

Lourenço, Vera; Herdling, Thorsten; Reich, Gabriele; Menezes, José C; Lochmann, Dirk

2011-08-01

A set of 192 fluid bed granulation batches at industrial scale were in-line monitored using microwave resonance technology (MRT) to determine moisture, temperature and density of the granules. Multivariate data analysis techniques such as multiway partial least squares (PLS), multiway principal component analysis (PCA) and multivariate batch control charts were applied onto collected batch data sets. The combination of all these techniques, along with off-line particle size measurements, led to significantly increased process understanding. A seasonality effect could be put into evidence that impacted further processing through its influence on the final granule size. Moreover, it was demonstrated by means of a PLS that a relation between the particle size and the MRT measurements can be quantitatively defined, highlighting a potential ability of the MRT sensor to predict information about the final granule size. This study has contributed to improve a fluid bed granulation process, and the process knowledge obtained shows that the product quality can be built in process design, following Quality by Design (QbD) and Process Analytical Technology (PAT) principles. Copyright © 2011. Published by Elsevier B.V.

Induced lexico-syntactic patterns improve information extraction from online medical forums.

PubMed

Gupta, Sonal; MacLean, Diana L; Heer, Jeffrey; Manning, Christopher D

2014-01-01

To reliably extract two entity types, symptoms and conditions (SCs), and drugs and treatments (DTs), from patient-authored text (PAT) by learning lexico-syntactic patterns from data annotated with seed dictionaries. Despite the increasing quantity of PAT (eg, online discussion threads), tools for identifying medical entities in PAT are limited. When applied to PAT, existing tools either fail to identify specific entity types or perform poorly. Identification of SC and DT terms in PAT would enable exploration of efficacy and side effects for not only pharmaceutical drugs, but also for home remedies and components of daily care. We use SC and DT term dictionaries compiled from online sources to label several discussion forums from MedHelp (http://www.medhelp.org). We then iteratively induce lexico-syntactic patterns corresponding strongly to each entity type to extract new SC and DT terms. Our system is able to extract symptom descriptions and treatments absent from our original dictionaries, such as 'LADA', 'stabbing pain', and 'cinnamon pills'. Our system extracts DT terms with 58-70% F1 score and SC terms with 66-76% F1 score on two forums from MedHelp. We show improvements over MetaMap, OBA, a conditional random field-based classifier, and a previous pattern learning approach. Our entity extractor based on lexico-syntactic patterns is a successful and preferable technique for identifying specific entity types in PAT. To the best of our knowledge, this is the first paper to extract SC and DT entities from PAT. We exhibit learning of informal terms often used in PAT but missing from typical dictionaries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Knowledge management in a waste based biorefinery in the QbD paradigm.

PubMed

Rathore, Anurag S; Chopda, Viki R; Gomes, James

2016-09-01

Shifting resource base from fossil feedstock to renewable raw materials for production of chemical products has opened up an area of novel applications of industrial biotechnology-based process tools. This review aims to provide a concise and focused discussion on recent advances in knowledge management to facilitate efficient and optimal operation of a biorefinery. Application of quality by design (QbD) and process analytical technology (PAT) as tools for knowledge creation and management at different levels has been highlighted. Role of process integration, government policies, knowledge exchange through collaboration, and use of databases and computational tools have also been touched upon. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi-parameter flow cytometry as a process analytical technology (PAT) approach for the assessment of bacterial ghost production.

PubMed

Langemann, Timo; Mayr, Ulrike Beate; Meitz, Andrea; Lubitz, Werner; Herwig, Christoph

2016-01-01

Flow cytometry (FCM) is a tool for the analysis of single-cell properties in a cell suspension. In this contribution, we present an improved FCM method for the assessment of E-lysis in Enterobacteriaceae. The result of the E-lysis process is empty bacterial envelopes-called bacterial ghosts (BGs)-that constitute potential products in the pharmaceutical field. BGs have reduced light scattering properties when compared with intact cells. In combination with viability information obtained from staining samples with the membrane potential-sensitive fluorescent dye bis-(1,3-dibutylarbituric acid) trimethine oxonol (DiBAC4(3)), the presented method allows to differentiate between populations of viable cells, dead cells, and BGs. Using a second fluorescent dye RH414 as a membrane marker, non-cellular background was excluded from the data which greatly improved the quality of the results. Using true volumetric absolute counting, the FCM data correlated well with cell count data obtained from colony-forming units (CFU) for viable populations. Applicability of the method to several Enterobacteriaceae (different Escherichia coli strains, Salmonella typhimurium, Shigella flexneri 2a) could be shown. The method was validated as a resilient process analytical technology (PAT) tool for the assessment of E-lysis and for particle counting during 20-l batch processes for the production of Escherichia coli Nissle 1917 BGs.

Reliability testing of a portfolio assessment tool for postgraduate family medicine training in South Africa

PubMed Central

Mash, Bob; Derese, Anselme

2013-01-01

Abstract Background Competency-based education and the validity and reliability of workplace-based assessment of postgraduate trainees have received increasing attention worldwide. Family medicine was recognised as a speciality in South Africa six years ago and a satisfactory portfolio of learning is a prerequisite to sit the national exit exam. A massive scaling up of the number of family physicians is needed in order to meet the health needs of the country. Aim The aim of this study was to develop a reliable, robust and feasible portfolio assessment tool (PAT) for South Africa. Methods Six raters each rated nine portfolios from the Stellenbosch University programme, using the PAT, to test for inter-rater reliability. This rating was repeated three months later to determine test–retest reliability. Following initial analysis and feedback the PAT was modified and the inter-rater reliability again assessed on nine new portfolios. An acceptable intra-class correlation was considered to be > 0.80. Results The total score was found to be reliable, with a coefficient of 0.92. For test–retest reliability, the difference in mean total score was 1.7%, which was not statistically significant. Amongst the subsections, only assessment of the educational meetings and the logbook showed reliability coefficients > 0.80. Conclusion This was the first attempt to develop a reliable, robust and feasible national portfolio assessment tool to assess postgraduate family medicine training in the South African context. The tool was reliable for the total score, but the low reliability of several sections in the PAT helped us to develop 12 recommendations regarding the use of the portfolio, the design of the PAT and the training of raters.

Towards better process understanding: chemometrics and multivariate measurements in manufacturing of solid dosage forms.

PubMed

Matero, Sanni; van Den Berg, Frans; Poutiainen, Sami; Rantanen, Jukka; Pajander, Jari

2013-05-01

The manufacturing of tablets involves many unit operations that possess multivariate and complex characteristics. The interactions between the material characteristics and process related variation are presently not comprehensively analyzed due to univariate detection methods. As a consequence, current best practice to control a typical process is to not allow process-related factors to vary i.e. lock the production parameters. The problem related to the lack of sufficient process understanding is still there: the variation within process and material properties is an intrinsic feature and cannot be compensated for with constant process parameters. Instead, a more comprehensive approach based on the use of multivariate tools for investigating processes should be applied. In the pharmaceutical field these methods are referred to as Process Analytical Technology (PAT) tools that aim to achieve a thorough understanding and control over the production process. PAT includes the frames for measurement as well as data analyzes and controlling for in-depth understanding, leading to more consistent and safer drug products with less batch rejections. In the optimal situation, by applying these techniques, destructive end-product testing could be avoided. In this paper the most prominent multivariate data analysis measuring tools within tablet manufacturing and basic research on operations are reviewed. Copyright © 2013 Wiley Periodicals, Inc.

Applicability of near-infrared spectroscopy in the monitoring of film coating and curing process of the prolonged release coated pellets.

PubMed

Korasa, Klemen; Hudovornik, Grega; Vrečer, Franc

2016-10-10

Although process analytical technology (PAT) guidance has been introduced to the pharmaceutical industry just a decade ago, this innovative approach has already become an important part of efficient pharmaceutical development, manufacturing, and quality assurance. PAT tools are especially important in technologically complex operations which require strict control of critical process parameters and have significant effect on final product quality. Manufacturing of prolonged release film coated pellets is definitely one of such processes. The aim of the present work was to study the applicability of the at-line near-infrared spectroscopy (NIR) approach in the monitoring of pellet film coating and curing steps. Film coated pellets were manufactured by coating the active ingredient containing pellets with film coating based on polymethacrylate polymers (Eudragit® RS/RL). The NIR proved as a useful tool for the monitoring of the curing process since it was able to determine the extent of the curing and hence predict drug release rate by using partial least square (PLS) model. However, such approach also showed a number of limitations, such as low reliability and high susceptibility to pellet moisture content, and was thus not able to predict drug release from pellets with high moisture content. On the other hand, the at-line NIR was capable to predict the thickness of Eudragit® RS/RL film coating in a wide range (up to 40μm) with good accuracy even in the pellets with high moisture content. To sum up, high applicability of the at-line NIR in the monitoring of the prolonged release pellets production was demonstrated in the present study. The present findings may contribute to more efficient and reliable PAT solutions in the manufacturing of prolonged release dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of in line monitored fluid bed granulation process parameters on the stability of Ethinylestradiol.

PubMed

Roßteuscher-Carl, Katrin; Fricke, Sabine; Hacker, Michael C; Schulz-Siegmund, Michaela

2015-12-30

Ethinylestradiol (EE) as a highly active and low dosed compound is prone to oxidative degradation. The stability of the drug substance is therefore a critical parameter that has to be considered during drug formulation. Beside the stability of the drug substance, granule particle size and moisture are critical quality attributes (CQA) of the fluid bed granulation process which influence the tableting ability of the resulting granules. Both CQA should therefore be monitored during the production process by process analytic technology (PAT) according to ICH Q8. This work focusses on the effects of drying conditions on the stability of EE in a fluid-bed granulation process. We quantified EE degradation products 6-alpha-hydroxy-EE, 6-beta-hydroxy-EE, 9(11)-dehydro-EE and 6-oxo-EE during long time storage and accelerated conditions. PAT-tools that monitor granule particle size (Spatial filtering technology) and granule moisture (Microwave resonance technology) were applied and compared with off-line methods. We found a relevant influence of residual granule moisture and thermic stress applied during granulation on the storage stability of EE, whereas no degradation was found immediately after processing. Hence we conclude that drying parameters have a relevant influence on long term EE stability. Copyright © 2015 Elsevier B.V. All rights reserved.

Bridging the gap between PAT concepts and implementation: An integrated software platform for fermentation.

PubMed

Chopda, Viki R; Gomes, James; Rathore, Anurag S

2016-01-01

Bioreactor control significantly impacts both the amount and quality of the product being manufactured. The complexity of the control strategy that is implemented increases with reactor size, which may vary from thousands to tens of thousands of litres in commercial manufacturing. The Process Analytical Technology (PAT) initiative has highlighted the need for having robust monitoring tools and effective control schemes that are capable of taking real time information about the critical quality attributes (CQA) and the critical process parameters (CPP) and executing immediate response as soon as a deviation occurs. However, the limited flexibility that present commercial software packages offer creates a hurdle. Visual programming environments have gradually emerged as potential alternatives to the available text based languages. This paper showcases development of an integrated programme using a visual programming environment for a Sartorius BIOSTAT® B Plus 5L bioreactor through which various peripheral devices are interfaced. The proposed programme facilitates real-time access to data and allows for execution of control actions to follow the desired trajectory. Major benefits of such integrated software system include: (i) improved real time monitoring and control; (ii) reduced variability; (iii) improved performance; (iv) reduced operator-training time; (v) enhanced knowledge management; and (vi) easier PAT implementation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Implementing PAT with Standards

NASA Astrophysics Data System (ADS)

Chandramohan, Laakshmana Sabari; Doolla, Suryanarayana; Khaparde, S. A.

2016-02-01

Perform Achieve Trade (PAT) is a market-based incentive mechanism to promote energy efficiency. The purpose of this work is to address the challenges inherent to inconsistent representation of business processes, and interoperability issues in PAT like cap-and-trade mechanisms especially when scaled. Studies by various agencies have highlighted that as the mechanism evolves including more industrial sectors and industries in its ambit, implementation will become more challenging. This paper analyses the major needs of PAT (namely tracking, monitoring, auditing & verifying energy-saving reports, and providing technical support & guidance to stakeholders); and how the aforesaid reasons affect them. Though current technologies can handle these challenges to an extent, standardization activities for implementation have been scanty for PAT and this work attempts to evolve them. The inconsistent modification of business processes, rules, and procedures across stakeholders, and interoperability among heterogeneous systems are addressed. This paper proposes the adoption of specifically two standards into PAT, namely Business Process Model and Notation for maintaining consistency in business process modelling, and Common Information Model (IEC 61970, 61968, 62325 combined) for information exchange. Detailed architecture and organization of these adoptions are reported. The work can be used by PAT implementing agencies, stakeholders, and standardization bodies.

Structural and functional photoacoustic molecular tomography aided by emerging contrast agents

PubMed Central

Nie, Liming

2015-01-01

Photoacoustic tomography (PAT) can offer structural, functional and molecular contrasts at scalable observation level. By ultrasonically overcoming the strong optical scattering, this imaging technology can reach centimeters penetration depth while retaining high spatial resolution in biological tissue. Recent extensive research has been focused on developing new contrast agents to improve the imaging sensitivity, specificity and efficiency. These emerging materials have substantially accelerated PAT applications in signal sensing, functional imaging, biomarker labeling and therapy monitoring etc. Here, the potentials of different optical probes as PAT contrast agents were elucidated. We first describe the instrumental embodiments and the measured functional parameters, then focus on emerging contrast agent-based PAT applications, and finally discuss the challenges and prospects. PMID:24967718

First Autonomous Recording of in situ Dissolved Oxygen from Free-ranging Fish

NASA Astrophysics Data System (ADS)

Coffey, D.; Holland, K.

2016-02-01

Biologging technology has enhanced our understanding of the ecology of marine animals and has been central to identifying how oceanographic conditions drive patterns in their distribution and behavior. Among these environmental influences, there is increasing recognition of the impact of dissolved oxygen on the distribution of marine animals. Understanding of the impact of oxygen on vertical and horizontal movements would be advanced by contemporaneous in situ measurements of dissolved oxygen from animal-borne sensors instead of relying on environmental data that may not have appropriate spatial or temporal resolution. Here we demonstrate the capabilities of dissolved oxygen pop-up satellite archival tags (DO-PATs) by presenting the results from calibration experiments and trial deployments of two prototype tags on bluntnose sixgill sharks (Hexanchus griseus). The DO-PATs provided fast, accurate, and stable measurements in calibration trials and demonstrated high correlation with vertical profiles obtained via traditional ship-borne oceanographic instruments. Deployments on bluntnose sixgill sharks recorded oxygen saturations as low as 9.4% and effectively captured the oceanography of the region when compared with World Ocean Atlas 2013 values. This is the first study to use an animal-borne device to autonomously measure and record in situ dissolved oxygen saturation from non-air-breathing marine animals. The DO-PATs maintained consistency over time and yielded measurements equivalent to industry standards for environmental sampling. Acquiring contemporaneous in situ measurements of dissolved oxygen saturation alongside temperature and depth data will greatly improve our ability to investigate the spatial ecology of marine animals and make informed predictions of the impacts of global climate change. The information returned from DO-PATs is relevant not only to the study of the ecology of marine animals but will also become a useful new tool for investigating the physical structure of the oceans.

Headspace solid-phase microextraction (HS-SPME) combined with GC-MS as a process analytical technology (PAT) tool for monitoring the cultivation of C. tetani.

PubMed

Ghader, Masoud; Shokoufi, Nader; Es-Haghi, Ali; Kargosha, Kazem

2018-04-15

Vaccine production is a biological process in which variation in time and output is inevitable. Thus, the application of Process Analytical Technologies (PAT) will be important in this regard. Headspace solid - phase microextraction (HS-SPME) coupled with GC-MS can be used as a PAT for process monitoring. This method is suitable to chemical profiling of volatile organic compounds (VOCs) emitted from microorganisms. Tetanus is a lethal disease caused by Clostridium tetani (C. tetani) bacterium and vaccination is an ultimate way to prevent this disease. In this paper, SPME fiber was used for the investigation of VOCs emerging from C. tetani during cultivation. Different types of VOCs such as sulfur-containing compounds were identified and some of them were selected as biomarkers for bioreactor monitoring during vaccine production. In the second step, the portable dynamic air sampling (PDAS) device was used as an interface for sampling VOCs by SPME fibers. The sampling procedure was optimized by face-centered central composite design (FC-CCD). The optimized sampling time and inlet gas flow rates were 10 min and 2 m L s -1 , respectively. PDAS was mounted in exhausted gas line of bioreactor and 42 samples of VOCs were prepared by SPME fibers in 7 days during incubation. Simultaneously, pH and optical density (OD) were evaluated to cultivation process which showed good correlations with the identified VOCs (>80%). This method could be used for VOCs sampling from off-gas of a bioreactor to monitoring of the cultivation process. Copyright © 2018. Published by Elsevier B.V.

Use of in-die powder densification parameters in the implementation of process analytical technologies for tablet production on industrial scale.

PubMed

Cespi, Marco; Perinelli, Diego R; Casettari, Luca; Bonacucina, Giulia; Caporicci, Giuseppe; Rendina, Filippo; Palmieri, Giovanni F

2014-12-30

The use of process analytical technologies (PAT) to ensure final product quality is by now a well established practice in pharmaceutical industry. To date, most of the efforts in this field have focused on development of analytical methods using spectroscopic techniques (i.e., NIR, Raman, etc.). This work evaluated the possibility of using the parameters derived from the processing of in-line raw compaction data (the forces and displacement of the punches) as a PAT tool for controlling the tableting process. To reach this goal, two commercially available formulations were used, changing the quantitative composition and compressing them on a fully instrumented rotary pressing machine. The Heckel yield pressure and the compaction energies, together with the tablets hardness and compaction pressure, were selected and evaluated as discriminating parameters in all the prepared formulations. The apparent yield pressure, as shown in the obtained results, has the necessary sensitivity to be effectively included in a PAT strategy to monitor the tableting process. Additional investigations were performed to understand the criticalities and the mechanisms beyond this performing parameter and the associated implications. Specifically, it was discovered that the efficiency of the apparent yield pressure depends on the nominal drug title, the drug densification mechanism and the error in pycnometric density. In this study, the potential of using some parameters derived from the compaction raw data has been demonstrated to be an attractive alternative and complementary method to the well established spectroscopic techniques to monitor and control the tableting process. The compaction data monitoring method is also easy to set up and very cost effective. Copyright © 2014 Elsevier B.V. All rights reserved.

In-line monitoring of pellet coating thickness growth by means of visual imaging.

PubMed

Oman Kadunc, Nika; Sibanc, Rok; Dreu, Rok; Likar, Boštjan; Tomaževič, Dejan

2014-08-15

Coating thickness is the most important attribute of coated pharmaceutical pellets as it directly affects release profiles and stability of the drug. Quality control of the coating process of pharmaceutical pellets is thus of utmost importance for assuring the desired end product characteristics. A visual imaging technique is presented and examined as a process analytic technology (PAT) tool for noninvasive continuous in-line and real time monitoring of coating thickness of pharmaceutical pellets during the coating process. Images of pellets were acquired during the coating process through an observation window of a Wurster coating apparatus. Image analysis methods were developed for fast and accurate determination of pellets' coating thickness during a coating process. The accuracy of the results for pellet coating thickness growth obtained in real time was evaluated through comparison with an off-line reference method and a good agreement was found. Information about the inter-pellet coating uniformity was gained from further statistical analysis of the measured pellet size distributions. Accuracy and performance analysis of the proposed method showed that visual imaging is feasible as a PAT tool for in-line and real time monitoring of the coating process of pharmaceutical pellets. Copyright © 2014 Elsevier B.V. All rights reserved.

Process Analytical Technology (PAT): batch-to-batch reproducibility of fermentation processes by robust process operational design and control.

PubMed

Gnoth, S; Jenzsch, M; Simutis, R; Lübbert, A

2007-10-31

The Process Analytical Technology (PAT) initiative of the FDA is a reaction on the increasing discrepancy between current possibilities in process supervision and control of pharmaceutical production processes and its current application in industrial manufacturing processes. With rigid approval practices based on standard operational procedures, adaptations of production reactors towards the state of the art were more or less inhibited for long years. Now PAT paves the way for continuous process and product improvements through improved process supervision based on knowledge-based data analysis, "Quality-by-Design"-concepts, and, finally, through feedback control. Examples of up-to-date implementations of this concept are presented. They are taken from one key group of processes in recombinant pharmaceutical protein manufacturing, the cultivations of genetically modified Escherichia coli bacteria.

Gold nanoparticles as a contrast agent for in vivo tumor imaging with photoacoustic tomography

NASA Astrophysics Data System (ADS)

Zhang, Q.; Iwakuma, N.; Sharma, P.; Moudgil, B. M.; Wu, C.; McNeill, J.; Jiang, H.; Grobmyer, S. R.

2009-09-01

Photoacoustic tomography (PAT) is a rapidly emerging non-invasive imaging technology that integrates the merits of high optical contrast with high ultrasound resolution. The ability to quantitatively and non-invasively image nanoparticles has important implications for the development of nanoparticles as in vivo cancer diagnostic and therapeutic agents. In this study, the ability of systemically administered poly(ethylene glycol)-coated (PEGylated) gold nanoparticles as a contrast agent for in vivo tumor imaging with PAT has been evaluated. We demonstrate that gold nanoparticles (20 and 50 nm) have high photoacoustic contrast as compared to mouse tissue ex vivo. Gold nanoparticles can be visualized in mice in vivo following subcutaneous administration using PAT. Following intravenous administration of PEGylated gold nanoparticles to tumor-bearing mice, accumulation of gold nanoparticles in tumors can be effectively imaged with PAT. With gold nanoparticles as a contrast agent, PAT has important potential applications in the image guided therapy of superficial tumors such as breast cancer, melanoma and Merkel cell carcinoma.

Linear-array-based photoacoustic tomography for label-free high-throughput detection and quantification of circulating melanoma tumor cell clusters

NASA Astrophysics Data System (ADS)

Hai, Pengfei; Zhou, Yong; Zhang, Ruiying; Ma, Jun; Li, Yang; Wang, Lihong V.

2017-03-01

Circulating tumor cell (CTC) clusters arise from multicellular grouping in the primary tumor and elevate the metastatic potential by 23 to 50 fold compared to single CTCs. High throughout detection and quantification of CTC clusters is critical for understanding the tumor metastasis process and improving cancer therapy. In this work, we report a linear-array-based photoacoustic tomography (LA-PAT) system capable of label-free high-throughput CTC cluster detection and quantification in vivo. LA-PAT detects CTC clusters and quantifies the number of cells in them based on the contrast-to-noise ratios (CNRs) of photoacoustic signals. The feasibility of LA-PAT was first demonstrated by imaging CTC clusters ex vivo. LA-PAT detected CTC clusters in the blood-filled microtubes and computed the number of cells in the clusters. The size distribution of the CTC clusters measured by LA-PAT agreed well with that obtained by optical microscopy. We demonstrated the ability of LA-PAT to detect and quantify CTC clusters in vivo by imaging injected CTC clusters in rat tail veins. LA-PAT detected CTC clusters immediately after injection as well as when they were circulating in the rat bloodstreams. Similarly, the numbers of cells in the clusters were computed based on the CNRs of the photoacoustic signals. The data showed that larger CTC clusters disappear faster than the smaller ones. The results prove the potential of LA-PAT as a promising tool for both preclinical tumor metastasis studies and clinical cancer therapy evaluation.

Match of psychosocial risk and psychosocial care in families of a child with cancer.

PubMed

Sint Nicolaas, S M; Schepers, S A; van den Bergh, E M M; de Boer, Y; Streng, I; van Dijk-Lokkart, E M; Grootenhuis, M A; Verhaak, C M

2017-12-01

The Psychosocial Assessment Tool (PAT) was developed to screen for psychosocial risk, aimed to be supportive in directing psychosocial care to families of a child with cancer. This study aimed to determine (i) the match between PAT risk score and provided psychosocial care with healthcare professionals blind to outcome of PAT assessment, and (ii) the match between PAT risk score and team risk estimation. Eighty-three families of children with cancer from four pediatric oncology centers in the Netherlands participated (59% response rate). The PAT and team risk estimation was assessed at diagnosis (M = 40.2 days, SD = 14.1 days), and the content of provided psychosocial care in the 5-month period thereafter resulting in basic or specialized care. According to the PAT, 65% of families were defined as having low (universal), 30% medium (targeted), and 5% high (clinical) risk for developing psychosocial problems. Thirty percent of patients from universal group got basic psychosocial care, 63% got specialized care, and 7% did not get any care. Fourteen percent of the families at risk got basic care, 86% got specialized care. Team risk estimations and PAT risk scores matched with 58% of the families. This study showed that families at risk, based on standardized risk assessment with the PAT, received more specialized care than families without risk. However, still 14% of the families with high risks only received basic care, and 63% of the families with standard risk got specialized care. Standardized risk assessment can be used as part of comprehensive care delivery, complementing the team. © 2017 Wiley Periodicals, Inc.

Photoacoustic Tomography

NASA Astrophysics Data System (ADS)

Wang, Lihong V.

Photoacoustic tomography (PAT) refers to imaging that is based on the photoacoustic effect. Although the photoacoustic effect as a physical phenomenon was first reported on by Alexander Graham Bell in 1880 [1], PAT as an imaging technology was developed only after the advent of ultrasonic transducers, computers, and lasers [2-31]. A review on biomedical photoacoustics is available [32]. The motivation for PAT is to combine optical-absorption contrast with ultrasonic spatial resolution for deep imaging in the optical quasi-diffusive or diffusive regime. In PAT, the tissue is irradiated by usually a short-pulsed laser beam to achieve a thermal and acoustic impulse response (Fig. 19.1). Locally absorbed light is converted into heat, which is further converted to a pressure rise via thermo-elastic expansion. The initial pressure rise - determined by the local optical absorption coefficient (μ â ), fluence (ψ) and other thermal and mechanical properties - propagates as an ultrasonic wave, which is referred to as a photoacoustic wave.

Pressure-assisted thermal sterilization of soup

NASA Astrophysics Data System (ADS)

Shibeshi, Kidane; Farid, Mohammed M.

2010-12-01

The overall efficiency of an existing scale-up pressure-assisted thermal sterilization (PATS) unit was investigated with regards to inactivation of Geobacillus stearothermophilus spores suspended in pumpkin soup. The PATS unit is a double pipe heat exchanger in which the soup is pumped into its inner high pressure tube and constrained by two high pressure valves, while steam is continuously passed through the annular region to heat the content. The technology is based on pressure generation by thermal expansion of the liquid in an enclosure. In this work, the addition of an air line to push the treated liquid food out of the existing PATS unit has improved the overall quality of the treated samples, as evidenced by achieving higher log reduction of the spores. Compared with thermal processing, the application of PATS shows the potential for lowering the thermal treatment temperature, offering improved food quality.

Back to basics: The effects of block vs. interleaved trial administration on pro- and anti-saccade performance

PubMed Central

Zeligman, Liran; Zivotofsky, Ari Z.

2017-01-01

The pro and anti-saccade task (PAT) is a widely used tool in the study of overt and covert attention with promising potential role in neurocognitive and psychiatric assessment. However, specific PAT protocols can vary significantly between labs, potentially resulting in large variations in findings across studies. In light of recent calls towards a standardization of PAT the current study's objective was to systematically and purposely evaluate the effects of block vs. interleaved administration—a fundamental consideration—on PAT measures in a within subject design. Additionally, this study evaluated whether measures of a Posner-type cueing paradigm parallels measures of the PAT paradigm. As hypothesized, results indicate that PAT performance is highly susceptible to administration mode. Interleaved mode resulted in larger error rates not only for anti (blocks: M = 22%; interleaved: M = 42%) but also for pro-saccades (blocks: M = 5%; interleaved: M = 12%). This difference between block and interleaved administration was significantly larger in anti-saccades compared to pro-saccades and cannot be attributed to a 'speed/accuracy tradeoff'. Interleaved mode produced larger pro and anti-saccade differences in error rates while block administration produced larger latency differences. Results question the reflexive nature of pro-saccades, suggesting they are not purely reflexive. These results were further discussed and compared to previous studies that included within subject data of blocks and interleaved trials. PMID:28222173

Implementation of transmission NIR as a PAT tool for monitoring drug transformation during HME processing.

PubMed

Islam, Muhammad T; Scoutaris, Nikolaos; Maniruzzaman, Mohammed; Moradiya, Hiren G; Halsey, Sheelagh A; Bradley, Michael S A; Chowdhry, Babur Z; Snowden, Martin J; Douroumis, Dennis

2015-10-01

The aim of the work reported herein was to implement process analytical technology (PAT) tools during hot melt extrusion (HME) in order to obtain a better understanding of the relationship between HME processing parameters and the extruded formulations. For the first time two in-line NIR probes (transmission and reflectance) have been coupled with HME to monitor the extrusion of the water insoluble drug indomethacin (IND) in the presence of Soluplus (SOL) or Kollidon VA64 hydrophilic polymers. In-line extrusion monitoring of sheets, produced via a specially designed die, was conducted at various drug/polymer ratios and processing parameters. Characterisation of the extruded transparent sheets was also undertaken by using DSC, XRPD and Raman mapping. Analysis of the experimental findings revealed the production of molecular solutions where IND is homogeneously blended (ascertained by Raman mapping) in the polymer matrices, as it acts as a plasticizer for both hydrophilic polymers. PCA analysis of the recorded NIR signals showed that the screw speed used in HME affects the recorded spectra but not the homogeneity of the embedded drug in the polymer sheets. The IND/VA64 and IND/SOL extruded sheets displayed rapid dissolution rates with 80% and 30% of the IND being released, respectively within the first 20min. Copyright © 2015 Elsevier B.V. All rights reserved.

Monitoring chemical reactions by low-field benchtop NMR at 45 MHz: pros and cons.

PubMed

Silva Elipe, Maria Victoria; Milburn, Robert R

2016-06-01

Monitoring chemical reactions is the key to controlling chemical processes where NMR can provide support. High-field NMR gives detailed structural information on chemical compounds and reactions; however, it is expensive and complex to operate. Conversely, low-field NMR instruments are simple and relatively inexpensive alternatives. While low-field NMR does not provide the detailed information as the high-field instruments as a result of their smaller chemical shift dispersion and the complex secondary coupling, it remains of practical value as a process analytical technology (PAT) tool and is complimentary to other established methods, such as ReactIR and Raman spectroscopy. We have tested a picoSpin-45 (currently under ThermoFisher Scientific) benchtop NMR instrument to monitor three types of reactions by 1D (1) H NMR: a Fischer esterification, a Suzuki cross-coupling, and the formation of an oxime. The Fischer esterification is a relatively simple reaction run at high concentration and served as proof of concept. The Suzuki coupling is an example of a more complex, commonly used reaction involving overlapping signals. Finally, the oxime formation involved a reaction in two phases that cannot be monitored by other PAT tools. Here, we discuss the pros and cons of monitoring these reactions at a low-field of 45 MHz by 1D (1) H NMR. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Pulsed laser diode photoacoustic tomography (PLD-PAT) system for fast in vivo imaging of small animal brain

NASA Astrophysics Data System (ADS)

Upputuri, Paul Kumar; Kalva, Sandeep Kumar; Moothanchery, Mohesh; Pramanik, Manojit

2017-03-01

In recent years, high-repetition rate pulsed laser diode (PLD) was used as an alternative to the Nd:YAG lasers for photoacoustic tomography (PAT). The use of PLD makes the overall PAT system, a low-cost, portable, and high frame rate imaging tool for preclinical applications. In this work, we will present a portable in vivo pulsed laser diode based photoacoustic tomography (PLD-PAT) system. The PLD is integrated inside a circular scanning geometry. The PLD can provide near-infrared ( 803 nm) pulses with pulse duration 136 ns, and pulse energy 1.4 mJ / pulse at 7 kHz repetition rate. The system will be demonstrated for in vivo fast imaging of small animal brain. To enhance the contrast of brain imaging, experiments will be carried out using contrast agents which have strong absorption around laser excitation wavelength. This low-cost, portable small animal brain imaging system could be very useful for brain tumor imaging and therapy.

Assessment of family psychosocial functioning in survivors of pediatric cancer using the PAT2.0.

PubMed

Gilleland, Jordan; Reed-Knight, Bonney; Brand, Sarah; Griffin, Anya; Wasilewski-Masker, Karen; Meacham, Lillian; Mertens, Ann

2013-09-01

This study aimed to examine clinical validity and utility of a screening measure for familial psychosocial risk, the Psychosocial Assessment Tool 2.0 (PAT2.0), among pediatric cancer survivors participating in long-term survivorship care. Caregivers (N=79) completed the PAT2.0 during their child's survivorship appointment. Caregivers also reported on family engagement in outpatient mental health treatment. Medical records were reviewed for treatment history and oncology provider initiated psychology consults. The internal consistency of the PAT2.0 total score in this survivorship sample was strong. Psychology was consulted by the oncology provider to see 53% of participant families, and families seen by psychology had significantly higher PAT2.0 total scores than families without psychology consults. PAT2.0 total scores and corresponding subscales were higher for patients, parents, and siblings enrolled in outpatient mental health services since treatment completion. Results were consistent with psychosocial risk categories presented within the Pediatric Psychosocial Preventative Health Model. Fifty-one percent of families presenting for survivorship care scored in the "universal" category, 34% scored in the "targeted" category, and 15% scored in the "clinical" category. Data indicate that the overall proportions of families experiencing "universal", "targeted", and "clinical" levels of familial distress may be constant from the time of diagnosis into survivorship care. Overall, the PAT2.0 demonstrated strong psychometric properties among survivors of pediatric cancer and shows promise as a psychosocial screening measure to facilitate more effective family support in survivorship care. Copyright © 2013 John Wiley & Sons, Ltd.

76 FR 31339 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-31

... extension of the currently approved tool for the collection of ambulatory care clinical performance measure...: Medicare Demonstration Ambulatory Care Quality Measure Performance Assessment Tool (``PAT''); Use: This... based system. This system will also provide a platform for developing tools to collect clinical quality...

In-line UV spectroscopy for the quantification of low-dose active ingredients during the manufacturing of pharmaceutical semi-solid and liquid formulations.

PubMed

Bostijn, N; Hellings, M; Van Der Veen, M; Vervaet, C; De Beer, T

2018-07-12

UltraViolet (UV) spectroscopy was evaluated as an innovative Process Analytical Technology (PAT) - tool for the in-line and real-time quantitative determination of low-dosed active pharmaceutical ingredients (APIs) in a semi-solid (gel) and a liquid (suspension) pharmaceutical formulation during their batch production process. The performance of this new PAT-tool (i.e., UV spectroscopy) was compared with an already more established PAT-method based on Raman spectroscopy. In-line UV measurements were carried out with an immersion probe while for the Raman measurements a non-contact PhAT probe was used. For both studied formulations, an in-line API quantification model was developed and validated per spectroscopic technique. The known API concentrations (Y) were correlated with the corresponding in-line collected preprocessed spectra (X) through a Partial Least Squares (PLS) regression. Each developed quantification method was validated by calculating the accuracy profile on the basis of the validation experiments. Furthermore, the measurement uncertainty was determined based on the data generated for the determination of the accuracy profiles. From the accuracy profile of the UV- and Raman-based quantification method for the gel, it was concluded that at the target API concentration of 2% (w/w), 95 out of 100 future routine measurements given by the Raman method will not deviate more than 10% (relative error) from the true API concentration, whereas for the UV method the acceptance limits of 10% were exceeded. For the liquid formulation, the Raman method was not able to quantify the API in the low-dosed suspension (0.09% (w/w) API). In contrast, the in-line UV method was able to adequately quantify the API in the suspension. This study demonstrated that UV spectroscopy can be adopted as a novel in-line PAT-technique for low-dose quantification purposes in pharmaceutical processes. Important is that none of the two spectroscopic techniques was superior to the other for both formulations: the Raman method was more accurate in quantifying the API in the gel (2% (w/w) API), while the UV method performed better for API quantification in the suspension (0.09% (w/w) API). Copyright © 2018 Elsevier B.V. All rights reserved.

Research on application of several tracking detectors in APT system

NASA Astrophysics Data System (ADS)

Liu, Zhi

2005-01-01

APT system is the key technology in free space optical communication system, and acquisition and tracking detector is the key component in PAT system. There are several candidate detectors that can be used in PAT system, such as CCD, QAPD and CMOS Imager etc. The characteristics of these detectors are quite different, i.e., the structures and the working schemes. This paper gives thoroughly compare of the usage and working principle of CCD and CMOS imager, and discusses the key parameters like tracking error, noise analyses, power analyses etc. Conclusion is given at the end of this paper that CMOS imager is a good candidate detector for PAT system in free space optical communication system.

Microalgal process-monitoring based on high-selectivity spectroscopy tools: status and future perspectives.

PubMed

Podevin, Michael; Fotidis, Ioannis A; Angelidaki, Irini

2018-08-01

Microalgae are well known for their ability to accumulate lipids intracellularly, which can be used for biofuels and mitigate CO 2 emissions. However, due to economic challenges, microalgae bioprocesses have maneuvered towards the simultaneous production of food, feed, fuel, and various high-value chemicals in a biorefinery concept. On-line and in-line monitoring of macromolecules such as lipids, proteins, carbohydrates, and high-value pigments will be more critical to maintain product quality and consistency for downstream processing in a biorefinery to maintain and valorize these markets. The main contribution of this review is to present current and prospective advances of on-line and in-line process analytical technology (PAT), with high-selectivity - the capability of monitoring several analytes simultaneously - in the interest of improving product quality, productivity, and process automation of a microalgal biorefinery. The high-selectivity PAT under consideration are mid-infrared (MIR), near-infrared (NIR), and Raman vibrational spectroscopies. The current review contains a critical assessment of these technologies in the context of recent advances in software and hardware in order to move microalgae production towards process automation through multivariate process control (MVPC) and software sensors trained on "big data". The paper will also include a comprehensive overview of off-line implementations of vibrational spectroscopy in microalgal research as it pertains to spectral interpretation and process automation to aid and motivate development.

A Process Analytical Technology (PAT) approach to control a new API manufacturing process: development, validation and implementation.

PubMed

Schaefer, Cédric; Clicq, David; Lecomte, Clémence; Merschaert, Alain; Norrant, Edith; Fotiadu, Frédéric

2014-03-01

Pharmaceutical companies are progressively adopting and introducing Process Analytical Technology (PAT) and Quality-by-Design (QbD) concepts promoted by the regulatory agencies, aiming the building of the quality directly into the product by combining thorough scientific understanding and quality risk management. An analytical method based on near infrared (NIR) spectroscopy was developed as a PAT tool to control on-line an API (active pharmaceutical ingredient) manufacturing crystallization step during which the API and residual solvent contents need to be precisely determined to reach the predefined seeding point. An original methodology based on the QbD principles was designed to conduct the development and validation of the NIR method and to ensure that it is fitted for its intended use. On this basis, Partial least squares (PLS) models were developed and optimized using chemometrics methods. The method was fully validated according to the ICH Q2(R1) guideline and using the accuracy profile approach. The dosing ranges were evaluated to 9.0-12.0% w/w for the API and 0.18-1.50% w/w for the residual methanol. As by nature the variability of the sampling method and the reference method are included in the variability obtained for the NIR method during the validation phase, a real-time process monitoring exercise was performed to prove its fit for purpose. The implementation of this in-process control (IPC) method on the industrial plant from the launch of the new API synthesis process will enable automatic control of the final crystallization step in order to ensure a predefined quality level of the API. In addition, several valuable benefits are expected including reduction of the process time, suppression of a rather difficult sampling and tedious off-line analyses. © 2013 Published by Elsevier B.V.

Using PAT to accelerate the transition to continuous API manufacturing.

PubMed

Gouveia, Francisca F; Rahbek, Jesper P; Mortensen, Asmus R; Pedersen, Mette T; Felizardo, Pedro M; Bro, Rasmus; Mealy, Michael J

2017-01-01

Significant improvements can be realized by converting conventional batch processes into continuous ones. The main drivers include reduction of cost and waste, increased safety, and simpler scale-up and tech transfer activities. Re-designing the process layout offers the opportunity to incorporate a set of process analytical technologies (PAT) embraced in the Quality-by-Design (QbD) framework. These tools are used for process state estimation, providing enhanced understanding of the underlying variability in the process impacting quality and yield. This work describes a road map for identifying the best technology to speed-up the development of continuous processes while providing the basis for developing analytical methods for monitoring and controlling the continuous full-scale reaction. The suitability of in-line Raman, FT-infrared (FT-IR), and near-infrared (NIR) spectroscopy for real-time process monitoring was investigated in the production of 1-bromo-2-iodobenzene. The synthesis consists of three consecutive reaction steps including the formation of an unstable diazonium salt intermediate, which is critical to secure high yield and avoid formation of by-products. All spectroscopic methods were able to capture critical information related to the accumulation of the intermediate with very similar accuracy. NIR spectroscopy proved to be satisfactory in terms of performance, ease of installation, full-scale transferability, and stability to very adverse process conditions. As such, in-line NIR was selected to monitor the continuous full-scale production. The quantitative method was developed against theoretical concentration values of the intermediate since representative sampling for off-line reference analysis cannot be achieved. The rapid and reliable analytical system allowed the following: speeding up the design of the continuous process and a better understanding of the manufacturing requirements to ensure optimal yield and avoid unreacted raw materials and by-products in the continuous reactor effluent. Graphical Abstract Using PAT to accelerate the transition to continuous API manufacturing.

Portable Automated Test Station: Using Engineering-Design Partnerships to Replace Obsolete Test Systems

DTIC Science & Technology

2015-04-01

troubleshooting avionics system faults while the aircraft is on the ground. The core component of the PATS-30, the ruggedized laptop, is no longer sustainable...as well as trouble shooting avionics system faults while the aircraft is on the ground. The PATS-70 utilizes up-to-date, sustainable technology for...Operational Flight Program (OFP) software loading and diagnostic avionics system testing and includes additional TPSs to enhance its capability

Combining two open source tools for neural computation (BioPatRec and Netlab) improves movement classification for prosthetic control.

PubMed

Prahm, Cosima; Eckstein, Korbinian; Ortiz-Catalan, Max; Dorffner, Georg; Kaniusas, Eugenijus; Aszmann, Oskar C

2016-08-31

Controlling a myoelectric prosthesis for upper limbs is increasingly challenging for the user as more electrodes and joints become available. Motion classification based on pattern recognition with a multi-electrode array allows multiple joints to be controlled simultaneously. Previous pattern recognition studies are difficult to compare, because individual research groups use their own data sets. To resolve this shortcoming and to facilitate comparisons, open access data sets were analysed using components of BioPatRec and Netlab pattern recognition models. Performances of the artificial neural networks, linear models, and training program components were compared. Evaluation took place within the BioPatRec environment, a Matlab-based open source platform that provides feature extraction, processing and motion classification algorithms for prosthetic control. The algorithms were applied to myoelectric signals for individual and simultaneous classification of movements, with the aim of finding the best performing algorithm and network model. Evaluation criteria included classification accuracy and training time. Results in both the linear and the artificial neural network models demonstrated that Netlab's implementation using scaled conjugate training algorithm reached significantly higher accuracies than BioPatRec. It is concluded that the best movement classification performance would be achieved through integrating Netlab training algorithms in the BioPatRec environment so that future prosthesis training can be shortened and control made more reliable. Netlab was therefore included into the newest release of BioPatRec (v4.0).

Temporal and spatial variation in personal ambient temperatures for outdoor working populations in the southeastern USA

NASA Astrophysics Data System (ADS)

Sugg, Margaret M.; Fuhrmann, Christopher M.; Runkle, Jennifer D.

2018-05-01

Excessive ambient temperature exposure can result in significant morbidity and mortality, especially among vulnerable occupational groups like outdoor workers. Average temperatures in the USA are projected to increase in frequency and intensity, placing future worker populations at greater risk for unhealthy levels of exposure. Unlike previous research focused on aggregate-level temperature exposures from in situ weather station data, this study will measure location-based personal ambient temperatures (PAT) at the individual-level by piloting the use of wearable sensor technology. A total of 66 outdoor workers in three geographically and climatologically diverse regions in the Southeast USA were continuously sampled during the workday for a 1-week period throughout July 11 to August 8 2016. Results indicate significant worker variation in temperature exposure within and between study locations; with PAT characterized by less pronounced variability as workers moved between indoor and outdoor environments. Developed land covers, a factor often associated with higher temperatures, were poorly correlated with PAT. Future analysis should focus on a worker's physiological response to PAT and mapping of spatial patterns of PAT for a larger worker population to produce innovative and targeted heat prevention programs.

Real-time determination of critical quality attributes using near-infrared spectroscopy: a contribution for Process Analytical Technology (PAT).

PubMed

Rosas, Juan G; Blanco, Marcel; González, Josep M; Alcalà, Manel

2012-08-15

Process Analytical Technology (PAT) is playing a central role in current regulations on pharmaceutical production processes. Proper understanding of all operations and variables connecting the raw materials to end products is one of the keys to ensuring quality of the products and continuous improvement in their production. Near infrared spectroscopy (NIRS) has been successfully used to develop faster and non-invasive quantitative methods for real-time predicting critical quality attributes (CQA) of pharmaceutical granulates (API content, pH, moisture, flowability, angle of repose and particle size). NIR spectra have been acquired from the bin blender after granulation process in a non-classified area without the need of sample withdrawal. The methodology used for data acquisition, calibration modelling and method application in this context is relatively inexpensive and can be easily implemented by most pharmaceutical laboratories. For this purpose, Partial Least-Squares (PLS) algorithm was used to calculate multivariate calibration models, that provided acceptable Root Mean Square Error of Predictions (RMSEP) values (RMSEP(API)=1.0 mg/g; RMSEP(pH)=0.1; RMSEP(Moisture)=0.1%; RMSEP(Flowability)=0.6 g/s; RMSEP(Angle of repose)=1.7° and RMSEP(Particle size)=2.5%) that allowed the application for routine analyses of production batches. The proposed method affords quality assessment of end products and the determination of important parameters with a view to understanding production processes used by the pharmaceutical industry. As shown here, the NIRS technique is a highly suitable tool for Process Analytical Technologies. Copyright © 2012 Elsevier B.V. All rights reserved.

Photoacoustic tomography guided diffuse optical tomography for small-animal model

NASA Astrophysics Data System (ADS)

Wang, Yihan; Gao, Feng; Wan, Wenbo; Zhang, Yan; Li, Jiao

2015-03-01

Diffuse optical tomography (DOT) is a biomedical imaging technology for noninvasive visualization of spatial variation about the optical properties of tissue, which can be applied to in vivo small-animal disease model. However, traditional DOT suffers low spatial resolution due to tissue scattering. To overcome this intrinsic shortcoming, multi-modal approaches that incorporate DOT with other imaging techniques have been intensively investigated, where a priori information provided by the other modalities is normally used to reasonably regularize the inverse problem of DOT. Nevertheless, these approaches usually consider the anatomical structure, which is different from the optical structure. Photoacoustic tomography (PAT) is an emerging imaging modality that is particularly useful for visualizing lightabsorbing structures embedded in soft tissue with higher spatial resolution compared with pure optical imaging. Thus, we present a PAT-guided DOT approach, to obtain the location a priori information of optical structure provided by PAT first, and then guide DOT to reconstruct the optical parameters quantitatively. The results of reconstruction of phantom experiments demonstrate that both quantification and spatial resolution of DOT could be highly improved by the regularization of feasible-region information provided by PAT.

A Review of PAT Strategies in Secondary Solid Oral Dosage Manufacturing of Small Molecules.

PubMed

Laske, Stephan; Paudel, Amrit; Scheibelhofer, Otto

2017-03-01

Pharmaceutical solid oral dosage product manufacturing is a well-established, yet revolutionizing area. To this end, process analytical technology (PAT) involves interdisciplinary and multivariate (chemical, physical, microbiological, and mathematical) methods for material (e.g., materials, intermediates, products) and process (e.g., temperature, pressure, throughput, etc.) analysis. This supports rational process modeling and enhanced control strategies for improved product quality and process efficiency. Therefore, it is often difficult to orient and find the relevant, integrated aspects of the current state-of-the-art. Especially, the link between fundamental research, in terms of sensor and control system development, to the application both in laboratory and manufacturing scale, is difficult to comprehend. This review compiles a nonexhaustive overview on current approaches from the recognized academia and industrial practices of PAT, including screening, selection, and final implementations in solid oral dosage manufacturing, through a wide diversity of use cases. Finally, the authors attempt to extract a common consensus toward developing PAT application guidance for different unit operations of drug product manufacturing. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

PAT: From Western solid dosage forms to Chinese materia medica preparations using NIR-CI.

PubMed

Zhou, Luwei; Xu, Manfei; Wu, Zhisheng; Shi, Xinyuan; Qiao, Yanjiang

2016-01-01

Near-infrared chemical imaging (NIR-CI) is an emerging technology that combines traditional near-infrared spectroscopy with chemical imaging. Therefore, NIR-CI can extract spectral information from pharmaceutical products and simultaneously visualize the spatial distribution of chemical components. The rapid and non-destructive features of NIR-CI make it an attractive process analytical technology (PAT) for identifying and monitoring critical control parameters during the pharmaceutical manufacturing process. This review mainly focuses on the pharmaceutical applications of NIR-CI in each unit operation during the manufacturing processes, from the Western solid dosage forms to the Chinese materia medica preparations. Finally, future applications of chemical imaging in the pharmaceutical industry are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

Set-up of a pump as turbine use in micro-pumped hydro energy storage: a case of study in Froyennes Belgium

NASA Astrophysics Data System (ADS)

Morabito, A.; Steimes, J.; Bontems, O.; Zohbi, G. Al; Hendrick, P.

2017-04-01

Its maturity makes pumped hydro energy storage (PHES) the most used technology in energy storage. Micro-hydro plants (<100 kW) are globally emerging due to further increases in the share of renewable electricity production such as wind and solar power. This paper presents the design of a micro-PHES developed in Froyennes, Belgium, using a pump as turbine (PaT) coupled with a variable frequency driver (VFD). The methods adopted for the selection of the most suitable pump for pumping and reverse mode are compared and discussed. Controlling and monitoring the PaT performances represent a compulsory design phase in the analysis feasibility of PaT coupled with VFD in micro PHES plant. This study aims at answering technical research aspects of µ-PHES site used with reversible pumps.

Review of the High Performance Antiproton Trap (HiPAT) Experiment

NASA Technical Reports Server (NTRS)

Martin, James J.; Lewis, Raymond A.; Pearson, J. Boise; Sims, W. Herb; Chakrabarti, Suman; Fant, Wallace E.; McDonald, Stan

2003-01-01

Many space propulsion concepts exist that use matter-antimatter reactions. Current antiproton production rates are enough to conduct proof-of-principle evaluation of these concepts. One enabling technology for such experiments is portable storage of low energy antiprotons, to transport antiprotons to experimental facilities. To address this need, HiPAT is being developed, with a design goal of containing 10(exp 12) particles for up to 18 days. HiPAT is a Penning-Malmberg trap with a 4 Tesla superconductor, 20kV electrodes, radio frequency (RF) network, and 10(exp -13) Torr vacuum. 'Normal' matter is being used to evaluate the system. An electron beam ionizes background gas in situ, and particle beams are captured dynamically. The experiment examines ion storage lifetimes, RF plasma diagnostics, charge exchange with background gases, and dynamic ion beam capture.

Unlocking interpretation in near infrared multivariate calibrations by orthogonal partial least squares.

PubMed

Stenlund, Hans; Johansson, Erik; Gottfries, Johan; Trygg, Johan

2009-01-01

Near infrared spectroscopy (NIR) was developed primarily for applications such as the quantitative determination of nutrients in the agricultural and food industries. Examples include the determination of water, protein, and fat within complex samples such as grain and milk. Because of its useful properties, NIR analysis has spread to other areas such as chemistry and pharmaceutical production. NIR spectra consist of infrared overtones and combinations thereof, making interpretation of the results complicated. It can be very difficult to assign peaks to known constituents in the sample. Thus, multivariate analysis (MVA) has been crucial in translating spectral data into information, mainly for predictive purposes. Orthogonal partial least squares (OPLS), a new MVA method, has prediction and modeling properties similar to those of other MVA techniques, e.g., partial least squares (PLS), a method with a long history of use for the analysis of NIR data. OPLS provides an intrinsic algorithmic improvement for the interpretation of NIR data. In this report, four sets of NIR data were analyzed to demonstrate the improved interpretation provided by OPLS. The first two sets included simulated data to demonstrate the overall principles; the third set comprised a statistically replicated design of experiments (DoE), to demonstrate how instrumental difference could be accurately visualized and correctly attributed to Wood's anomaly phenomena; the fourth set was chosen to challenge the MVA by using data relating to powder mixing, a crucial step in the pharmaceutical industry prior to tabletting. Improved interpretation by OPLS was demonstrated for all four examples, as compared to alternative MVA approaches. It is expected that OPLS will be used mostly in applications where improved interpretation is crucial; one such area is process analytical technology (PAT). PAT involves fewer independent samples, i.e., batches, than would be associated with agricultural applications; in addition, the Food and Drug Administration (FDA) demands "process understanding" in PAT. Both these issues make OPLS the ideal tool for a multitude of NIR calibrations. In conclusion, OPLS leads to better interpretation of spectrometry data (e.g., NIR) and improved understanding facilitates cross-scientific communication. Such improved knowledge will decrease risk, with respect to both accuracy and precision, when using NIR for PAT applications.

In-line moisture monitoring in fluidized bed granulation using a novel multi-resonance microwave sensor.

PubMed

Peters, Johanna; Bartscher, Kathrin; Döscher, Claas; Taute, Wolfgang; Höft, Michael; Knöchel, Reinhard; Breitkreutz, Jörg

2017-08-01

Microwave resonance technology (MRT) is known as a process analytical technology (PAT) tool for moisture measurements in fluid-bed granulation. It offers a great potential for wet granulation processes even where the suitability of near-infrared (NIR) spectroscopy is limited, e.g. colored granules, large variations in bulk density. However, previous sensor systems operating around a single resonance frequency showed limitations above approx. 7.5% granule moisture. This paper describes the application of a novel sensor working with four resonance frequencies. In-line data of all four resonance frequencies were collected and further processed. Based on calculation of density-independent microwave moisture values multiple linear regression (MLR) models using Karl-Fischer titration (KF) as well as loss on drying (LOD) as reference methods were build. Rapid, reliable in-process moisture control (RMSEP≤0.5%) even at higher moisture contents was achieved. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Jacobs, R

The Physics and Advanced Technologies (PAT) Directorate was created in July 2000 by Bruce Tarter, Director of Lawrence Livermore National Laboratory (LLNL). The Director called for the new organization to execute and support programs that apply cutting-edge physics and advanced technology to develop integrated solutions to problems in national security, fusion energy, information science, health care, and other national grand challenges. When I was appointed a year later as the PAT Directorate's first Associate Director, I initiated a strategic planning project to develop a vision, mission, and long-term goals for the Directorate. We adopted the goal of becoming a leadermore » in frontier physics and technology for twenty-first-century national security missions: Stockpile Stewardship, homeland security, energy independence, and the exploration of space. Our mission is to: (1) Help ensure the scientific excellence and vitality of the major LLNL programs through its leadership role in performing basic and applied multidisciplinary research and development with programmatic impact, and by recruiting and retaining science and technology leaders; (2) Create future opportunities and directions for LLNL and its major programs by growing new program areas and cutting-edge capabilities that are synergistic with, and supportive of, its national security mission; (3) Provide a direct conduit to the academic and high-tech industrial sectors for LLNL and its national security programs, through which the Laboratory gains access to frontier science and technology, and can impact the science and technology communities; (4) Leverage unique Laboratory capabilities, to advance the state universe. This inaugural PAT Annual Report begins a series that will chronicle our progress towards fulfilling this mission. I believe the report demonstrates that the PAT Directorate has a strong base of capabilities and accomplishments on which to build in meeting its goals. Some of the highlights include: (1) Leadership of the Laboratory's Physical Data Research Program that provides fundamental physics information for the Stockpile Stewardship Program. (2) Development of the handheld Microbead Immunoassay Dipstick System that will allow relatively untrained first-responders to run sophisticated onsite diagnostics for pathogens, including those associated with biowarfare agents, by using a simple, one-step measurement. (3) Major advances in target design for inertial fusion energy research using both laser and ion-beam drivers. (4) Development of the Advanced Technology Kill Vehicle concept for use as a high-performance interceptor in a broad range of missile defense programs. Over the course of the past decade, the Laboratory has seen its major program evolve from weapons research, development, and testing, to Stockpile Stewardship. Today, the country's national security priorities are changing rapidly: nuclear security is becoming a broader set of missions, and the Laboratory is being asked to contribute to a range of new mission areas from countering bioterrorism to ensuring information security. As we embark on the twenty-first century, the new PAT Directorate is poised to help lead the Laboratory's response to the country's changing national security needs.« less

Development of Process Analytical Technology (PAT) methods for controlled release pellet coating.

PubMed

Avalle, P; Pollitt, M J; Bradley, K; Cooper, B; Pearce, G; Djemai, A; Fitzpatrick, S

2014-07-01

This work focused on the control of the manufacturing process for a controlled release (CR) pellet product, within a Quality by Design (QbD) framework. The manufacturing process was Wurster coating: firstly layering active pharmaceutical ingredient (API) onto sugar pellet cores and secondly a controlled release (CR) coating. For each of these two steps, development of a Process Analytical Technology (PAT) method is discussed and also a novel application of automated microscopy as the reference method. Ultimately, PAT methods should link to product performance and the two key Critical Quality Attributes (CQAs) for this CR product are assay and release rate, linked to the API and CR coating steps respectively. In this work, the link between near infra-red (NIR) spectra and those attributes was explored by chemometrics over the course of the coating process in a pilot scale industrial environment. Correlations were built between the NIR spectra and coating weight (for API amount), CR coating thickness and dissolution performance. These correlations allow the coating process to be monitored at-line and so better control of the product performance in line with QbD requirements. Copyright © 2014 Elsevier B.V. All rights reserved.

In line NIR quantification of film thickness on pharmaceutical pellets during a fluid bed coating process.

PubMed

Lee, Min-Jeong; Seo, Da-Young; Lee, Hea-Eun; Wang, In-Chun; Kim, Woo-Sik; Jeong, Myung-Yung; Choi, Guang J

2011-01-17

Along with the risk-based approach, process analytical technology (PAT) has emerged as one of the key elements to fully implement QbD (quality-by-design). Near-infrared (NIR) spectroscopy has been extensively applied as an in-line/on-line analytical tool in biomedical and chemical industries. In this study, the film thickness on pharmaceutical pellets was examined for quantification using in-line NIR spectroscopy during a fluid-bed coating process. A precise monitoring of coating thickness and its prediction with a suitable control strategy is crucial to the quality assurance of solid dosage forms including dissolution characteristics. Pellets of a test formulation were manufactured and coated in a fluid-bed by spraying a hydroxypropyl methylcellulose (HPMC) coating solution. NIR spectra were acquired via a fiber-optic probe during the coating process, followed by multivariate analysis utilizing partial least squares (PLS) calibration models. The actual coating thickness of pellets was measured by two separate methods, confocal laser scanning microscopy (CLSM) and laser diffraction particle size analysis (LD-PSA). Both characterization methods gave superb correlation results, and all determination coefficient (R(2)) values exceeded 0.995. In addition, a prediction coating experiment for 70min demonstrated that the end-point can be accurately designated via NIR in-line monitoring with appropriate calibration models. In conclusion, our approach combining in-line NIR monitoring with CLSM and LD-PSA can be applied as an effective PAT tool for fluid-bed pellet coating processes. Copyright © 2010 Elsevier B.V. All rights reserved.

The effect of process parameters on audible acoustic emissions from high-shear granulation.

PubMed

Hansuld, Erin M; Briens, Lauren; Sayani, Amyn; McCann, Joe A B

2013-02-01

Product quality in high-shear granulation is easily compromised by minor changes in raw material properties or process conditions. It is desired to develop a process analytical technology (PAT) that can monitor the process in real-time and provide feedback for quality control. In this work, the application of audible acoustic emissions (AAEs) as a PAT tool was investigated. A condenser microphone was placed at the top of the air exhaust on a PMA-10 high-shear granulator to collect AAEs for a design of experiment (DOE) varying impeller speed, total binder volume and spray rate. The results showed the 10 Hz total power spectral densities (TPSDs) between 20 and 250 Hz were significantly affected by the changes in process conditions. Impeller speed and spray rate were shown to have statistically significant effects on granulation wetting, and impeller speed and total binder volume were significant in terms of process end-point. The DOE results were confirmed by a multivariate PLS model of the TPSDs. The scores plot showed separation based on impeller speed in the first component and spray rate in the second component. The findings support the use of AAEs to monitor changes in process conditions in real-time and achieve consistent product quality.

OLEM Performance Assessment Information

EPA Pesticide Factsheets

This asset includes a variety of data sets that measure the performance of Office of Land and Emergency Management (OLEM) programs in support of the Office of the Chief Financial Officer's Annual Commitment System (ACS) and Performance Evaluation Reporting System (PERS). Information is drawn from OLEM's ACRES, RCRAInfo, CERCLIS/SEMS, ICIS, and LUST4 systems, as well as input manually by authorized individuals in OLEM's program offices. Information is reviewed by OLEM program staff prior to being pushed to ACS and entered into PERS. This data asset also pulls in certain performance information input directly by Regional Office staff into ACS. Information is managed by the Performance Assessment Tool (PAT) and displayed in the PAT Dashboard.Information in this asset include:--Government Performance and Results Act (GPRA) of 1993: Measures reported for Innovations, Partnerships and Communications Office (IPCO), the Office of Brownfields and Land Revitalization (OBLR), the Office of Emergency Management (OEM), the Office of Resource Conservation and Recovery (ORCR), the Office of Superfund Remediation and Technology Innovation (OSRTI), and the Office of Underground Storage Tanks (OUST).-- Performance and Environmental Results System (PERS): Includes OLEM's information on performance results and baselines for the EPA Annual Plan and Budget.--Key Performance Indicators: OLEM has identified five KPIs that are tracked annually.--Integrated Cleanup Initiative: A pilot pe

Searching RNA motifs and their intermolecular contacts with constraint networks.

PubMed

Thébault, P; de Givry, S; Schiex, T; Gaspin, C

2006-09-01

Searching RNA gene occurrences in genomic sequences is a task whose importance has been renewed by the recent discovery of numerous functional RNA, often interacting with other ligands. Even if several programs exist for RNA motif search, none exists that can represent and solve the problem of searching for occurrences of RNA motifs in interaction with other molecules. We present a constraint network formulation of this problem. RNA are represented as structured motifs that can occur on more than one sequence and which are related together by possible hybridization. The implemented tool MilPat is used to search for several sRNA families in genomic sequences. Results show that MilPat allows to efficiently search for interacting motifs in large genomic sequences and offers a simple and extensible framework to solve such problems. New and known sRNA are identified as H/ACA candidates in Methanocaldococcus jannaschii. http://carlit.toulouse.inra.fr/MilPaT/MilPat.pl.

Increases in efficiency and enhancements to the Mars Observer non-stored commanding process

NASA Technical Reports Server (NTRS)

Brooks, Robert N., Jr.; Torgerson, J. Leigh

1994-01-01

The Mars Observer team was, until the untimely loss of the spacecraft on August 21, 1993, performing flight operations with greater efficiency and speed than any previous JPL mission of its size. This level of through-put was made possible by a mission operations system which was composed of skilled personnel using sophisticated sequencing and commanding tools. During cruise flight operations, however, it was realized by the project that this commanding level was not going to be sufficient to support the activities planned for mapping operations. The project had committed to providing the science instrument principle investigators with a much higher level of commanding during mapping. Thus, the project began taking steps to enhance the capabilities of the flight team. One mechanism used by project management was a tool available from total quality management (TQM). This tool is known as a process action team (PAT). The Mars Observer PAT was tasked to increase the capacity of the flight team's nonstored commanding process by fifty percent with no increase in staffing and a minimal increase in risk. The outcome of this effort was, in fact, to increase the capacity by a factor of 2.5 rather than the desired fifty percent and actually reduce risk. The majority of these improvements came from the automation of the existing command process. These results required very few changes to the existing mission operations system. Rather, the PAT was able to take advantage of automation capabilities inherent in the existing system and make changes to the existing flight team procedures.

Oracle Applications Patch Administration Tool (PAT) Beta Version

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

2002-01-04

PAT is a Patch Administration Tool that provides analysis, tracking, and management of Oracle Application patches. This includes capabilities as outlined below: Patch Analysis & Management Tool Outline of capabilities: Administration Patch Data Maintenance -- track Oracle Application patches applied to what database instance & machine Patch Analysis capture text files (readme.txt and driver files) form comparison detail report comparison detail PL/SQL package comparison detail SQL scripts detail JSP module comparison detail Parse and load the current applptch.txt (10.7) or load patch data from Oracle Application database patch tables (11i) Display Analysis -- Compare patch to be applied with currentmore » Oracle Application installed Appl_top code versions Patch Detail Module comparison detail Analyze and display one Oracle Application module patch. Patch Management -- automatic queue and execution of patches Administration Parameter maintenance -- setting for directory structure of Oracle Application appl_top Validation data maintenance -- machine names and instances to patch Operation Patch Data Maintenance Schedule a patch (queue for later execution) Run a patch (queue for immediate execution) Review the patch logs Patch Management Reports« less

Demonstration of Plasma Arc Environmental Technology Applications for the Demilitrization of DOD Stockpiles

NASA Technical Reports Server (NTRS)

Smith, Ed; Dee, P. E.; Zaghloul, Hany; Filius, Krag; Rivers, Tim

2000-01-01

Since 1989 the US Army Construction Engineering Research Laboratories (USACERL) have been active participants in the research and development towards establishing Plasma Arc Technology (PAT) as an efficient, economical, and safe hazardous waste immobilization tool. A plasma torch capable of generating high temperatures makes this technology a viable and powerful tool for the thermal destruction of various military industrial waste streams into an innocuous ceramic material no longer requiring hazardous waste landfill disposal. The emerging plasma environmental thermal treatment process has been used to safely and efficiently meet the waste disposal needs for various demilitarized components disposal needs, such as: (1) pyrotechnic smoke assemblies, (2) thermal batteries, (3) proximity fuses, (4) cartridge actuated devices (CADs), and (5) propellant actuated devices (PADs). MSE Technology Applications, Inc., (MSE) has proposed and fabricated a Mobile Plasma Treatment System to be a technology demonstrator for pilotscale mobile plasma waste processing. The system is capable of providing small-scale waste remediation services, and conducting waste stream applicability demonstrations. The Mobile Plasma Treatment System's innovative concept provides the flexibility to treat waste streams at numerous sites and sites with only a limited quantity of waste, yet too hazardous to transport to a regional fixed facility. The system was designed to be operated as skid mounted modules; consisting of a furnace module, controls module, offgas module, and ancillary systems module. All system components have been integrated to be operated from a single control station with both semi-continuous feeding and batch slag-pouring capability.

Demonstration of Plasma Arc Environmental Technology Applications for the Demilitarization of DOD Stockpiles

NASA Technical Reports Server (NTRS)

Smith, Ed; Zaghloul, Hany; Filius, Krag; Rivers, Tim

2000-01-01

Since 1989 the U.S. Army Construction Engineering Research Laboratories (USACERL) have been active participants in the research and development toward establishing Plasma Arc Technology (PAT) as an efficient, economical, and safe hazardous waste immobilization tool. A plasma torch capable of generating high temperatures makes this technology a viable and powerful tool for the thermal destruction of various military industrial waste streams into an innocuous ceramic material no longer requiring hazardous waste landfill (Class 1) disposal. The emerging pl asma environmental thermal treatment process, has been used to safely and efficiently meet the waste disposal needs for various demilitarized components disposal needs, such as: pyrotechnic smoke assemblies, thermal batteries, proximity fuses, cartridge actuated devices (CAD's), and propellant actuated devices (PAD's). MSE Technology Applications, Inc., (MSE) has proposed and fabricated a Mobile Plasma Treatment System to be a technology demonstrator for pilot-scale mobile plasma waste processing. The system is capable of providing small-scale waste remediation services, and conducting waste stream applicability demonstrations. The Mobile Plasma Treatment System's innovative concept provides the flexibility to treat waste streams at numerous sites and sites with only a limited quantity of waste, yet too hazardous to transport to a regional fixed facility. The system was designed to be operated as skid mounted modules; consisting of a furnace module, controls module, offgas module, and ancillary systems module. All system components have been integrated to be operated from a single control station with both semi-continuous feeding and batch slag-pouring capability.

Strategic funding priorities in the pharmaceutical sciences allied to Quality by Design (QbD) and Process Analytical Technology (PAT).

PubMed

Aksu, Buket; De Beer, Thomas; Folestad, Staffan; Ketolainen, Jarkko; Lindén, Hans; Lopes, Joao Almeida; de Matas, Marcel; Oostra, Wim; Rantanen, Jukka; Weimer, Marco

2012-09-29

Substantial changes in Pharmaceutical R&D strategy are required to address existing issues of low productivity, imminent patent expirations and pressures on pricing. Moves towards personalized healthcare and increasing diversity in the nature of portfolios including the rise of biopharmaceuticals however have the potential to provide considerable challenges to the establishment of cost effective and robust supply chains. To guarantee product quality and surety of supply for essential medicines it is necessary that manufacturing science keeps pace with advances in pharmaceutical R&D. In this position paper, the EUFEPS QbD and PAT Sciences network make recommendations that European industry, academia and health agencies focus attention on delivering step changes in science and technology in a number of key themes. These subject areas, all underpinned by the sciences allied to QbD and PAT, include product design and development for personalized healthcare, continuous-processing in pharmaceutical product manufacture, quantitative quality risk assessment for pharmaceutical development including life cycle management and the downstream processing of biopharmaceutical products. Plans are being established to gain commitment for inclusion of these themes into future funding priorities for the Innovative Medicines Initiative (IMI). Copyright © 2012 Elsevier B.V. All rights reserved.

Unveiling the geography of historical patents in the United States from 1836 to 1975

PubMed Central

Petralia, Sergio; Balland, Pierre-Alexandre; Rigby, David L.

2016-01-01

It is clear that technology is a key driver of economic growth. Much less clear is where new technologies are produced and how the geography of U.S. invention has changed over the last two hundred years. Patent data report the geography, history, and technological characteristics of invention. However, those data have only recently become available in digital form and at the present time there exists no comprehensive dataset on the geography of knowledge production in the United States prior to 1975. The database presented in this paper unveils the geography of historical patents granted by the United States Patent and Trademark Office (USPTO) from 1836 to 1975. This historical dataset, HistPat, is constructed using digitalized records of original patent documents that are publicly available. We describe a methodological procedure that allows recovery of geographical information on patents from the digital records. HistPat can be used in different disciplines ranging from geography, economics, history, network science, and science and technology studies. Additionally, it is easily merged with post-1975 USPTO digital patent data to extend it until today. PMID:27576103

In-line and real-time process monitoring of a freeze drying process using Raman and NIR spectroscopy as complementary process analytical technology (PAT) tools.

PubMed

De Beer, T R M; Vercruysse, P; Burggraeve, A; Quinten, T; Ouyang, J; Zhang, X; Vervaet, C; Remon, J P; Baeyens, W R G

2009-09-01

The aim of the present study was to examine the complementary properties of Raman and near infrared (NIR) spectroscopy as PAT tools for the fast, noninvasive, nondestructive and in-line process monitoring of a freeze drying process. Therefore, Raman and NIR probes were built in the freeze dryer chamber, allowing simultaneous process monitoring. A 5% (w/v) mannitol solution was used as model for freeze drying. Raman and NIR spectra were continuously collected during freeze drying (one Raman and NIR spectrum/min) and the spectra were analyzed using principal component analysis (PCA) and multivariate curve resolution (MCR). Raman spectroscopy was able to supply information about (i) the mannitol solid state throughout the entire process, (ii) the endpoint of freezing (endpoint of mannitol crystallization), and (iii) several physical and chemical phenomena occurring during the process (onset of ice nucleation, onset of mannitol crystallization). NIR spectroscopy proved to be a more sensitive tool to monitor the critical aspects during drying: (i) endpoint of ice sublimation and (ii) monitoring the release of hydrate water during storage. Furthermore, via NIR spectroscopy some Raman observations were confirmed: start of ice nucleation, end of mannitol crystallization and solid state characteristics of the end product. When Raman and NIR monitoring were performed on the same vial, the Raman signal was saturated during the freezing step caused by reflected NIR light reaching the Raman detector. Therefore, NIR and Raman measurements were done on a different vial. Also the importance of the position of the probes (Raman probe above the vial and NIR probe at the bottom of the sidewall of the vial) in order to obtain all required critical information is outlined. Combining Raman and NIR spectroscopy for the simultaneous monitoring of freeze drying allows monitoring almost all critical freeze drying process aspects. Both techniques do not only complement each other, they also provided mutual confirmation of specific conclusions.

X-PAT: a multiplatform patient referral data management system for small healthcare institution requirements.

PubMed

Masseroli, Marco; Marchente, Mario

2008-07-01

We present X-PAT, a platform-independent software prototype that is able to manage patient referral multimedia data in an intranet network scenario according to the specific control procedures of a healthcare institution. It is a self-developed storage framework based on a file system, implemented in eXtensible Markup Language (XML) and PHP Hypertext Preprocessor Language, and addressed to the requirements of limited-dimension healthcare entities (small hospitals, private medical centers, outpatient clinics, and laboratories). In X-PAT, healthcare data descriptions, stored in a novel Referral Base Management System (RBMS) according to Health Level 7 Clinical Document Architecture Release 2 (CDA R2) standard, can be easily applied to the specific data and organizational procedures of a particular healthcare working environment thanks also to the use of standard clinical terminology. Managed data, centralized on a server, are structured in the RBMS schema using a flexible patient record and CDA healthcare referral document structures based on XML technology. A novel search engine allows defining and performing queries on stored data, whose rapid execution is ensured by expandable RBMS indexing structures. Healthcare personnel can interface the X-PAT system, according to applied state-of-the-art privacy and security measures, through friendly and intuitive Web pages that facilitate user acceptance.

Strategic framework for education and training in Quality by Design (QbD) and process analytical technology (PAT).

PubMed

de Matas, Marcel; De Beer, Thomas; Folestad, Staffan; Ketolainen, Jarkko; Lindén, Hans; Lopes, João Almeida; Oostra, Wim; Weimer, Marco; Öhrngren, Per; Rantanen, Jukka

2016-07-30

The regulatory and technical landscape of the pharmaceutical field is rapidly evolving from one focused predominantly on development of small molecules, using well established manufacturing technologies towards an environment in which biologicals and complex modalities are being developed using advanced science and technology coupled with the application of modern Quality by Design (QbD) principles. In order that Europe keeps pace with these changes and sustains its position as major player in the development and commercialization of medicines, it is essential that measures are put in place to maintain a highly skilled workforce. A number of challenges however exist to equipping academic, industrial and health agency staff with the requisite knowledge, skills and experience to develop the next generation of medicines. In this regard, the EUFEPS QbD and PAT Sciences Network has proposed a structured framework for education, training and continued professional development, which comprises a number of pillars covering the fundamental principles of modern pharmaceutical development including the underpinning aspects of science, engineering and technology innovation. The framework is not prescriptive and is not aimed at describing specific course content in detail. It should however be used as a point of reference for those institutions delivering pharmaceutical based educational courses, to ensure that the necessary skills, knowledge and experience for successful pharmaceutical development are maintained. A positive start has been made and a number of examples of formal higher education courses and short training programs containing elements of this framework have been described. The ultimate vision for this framework however, is to see widespread adoption and proliferation of this curriculum with it forming the backbone of QbD and PAT science based skills development. Copyright © 2016 Elsevier B.V. All rights reserved.

Review of the High Performance Antiproton Trap (HiPAT) Experiment at the Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Pearson, J. B.; Sims, Herb; Martin, James; Chakrabarti, Suman; Lewis, Raymond; Fant, Wallace

2003-01-01

The significant energy density of matter-antimatter annihilation is attractive to the designers of future space propulsion systems, with the potential to offer a highly compact source of power. Many propulsion concepts exist that could take advantage of matter-antimatter reactions, and current antiproton production rates are sufficient to support basic proof-of-principle evaluation of technology associated with antimatter- derived propulsion. One enabling technology for such experiments is portable storage of low energy antiprotons, allowing antiprotons to be trapped, stored, and transported for use at an experimental facility. To address this need, the Marshall Space Flight Center's Propulsion Research Center is developing a storage system referred to as the High Performance Antiproton Trap (HiPAT) with a design goal of containing 10(exp 12) particles for up to 18 days. The HiPAT makes use of an electromagnetic system (Penning- Malmberg design) consisting of a 4 Telsa superconductor, high voltage electrode structure, radio frequency (RF) network, and ultra high vacuum system. To evaluate the system normal matter sources (both electron guns and ion sources) are used to generate charged particles. The electron beams ionize gas within the trapping region producing ions in situ, whereas the ion sources produce the particles external to the trapping region and required dynamic capture. A wide range of experiments has been performed examining factors such as ion storage lifetimes, effect of RF energy on storage lifetime, and ability to routinely perform dynamic ion capture. Current efforts have been focused on improving the FW rotating wall system to permit longer storage times and non-destructive diagnostics of stored ions. Typical particle detection is performed by extracting trapped ions from HiPAT and destructively colliding them with a micro-channel plate detector (providing number and energy information). This improved RF system has been used to detect various plasma modes for both electron and ion plasmas in the two traps at MSFC, including axial, cyclotron, and diocotron modes. New diagnostics are also being added to HiPAT to measure the axial density distribution of the trapped cloud to match measured RF plasma modes to plasma conditions.

Energy-based culture medium design for biomanufacturing optimization: A case study in monoclonal antibody production by GS-NS0 cells.

PubMed

Quiroga-Campano, Ana L; Panoskaltsis, Nicki; Mantalaris, Athanasios

2018-03-02

Demand for high-value biologics, a rapidly growing pipeline, and pressure from competition, time-to-market and regulators, necessitate novel biomanufacturing approaches, including Quality by Design (QbD) principles and Process Analytical Technologies (PAT), to facilitate accelerated, efficient and effective process development platforms that ensure consistent product quality and reduced lot-to-lot variability. Herein, QbD and PAT principles were incorporated within an innovative in vitro-in silico integrated framework for upstream process development (UPD). The central component of the UPD framework is a mathematical model that predicts dynamic nutrient uptake and average intracellular ATP content, based on biochemical reaction networks, to quantify and characterize energy metabolism and its adaptive response, metabolic shifts, to maintain ATP homeostasis. The accuracy and flexibility of the model depends on critical cell type/product/clone-specific parameters, which are experimentally estimated. The integrated in vitro-in silico platform and the model's predictive capacity reduced burden, time and expense of experimentation resulting in optimal medium design compared to commercially available culture media (80% amino acid reduction) and a fed-batch feeding strategy that increased productivity by 129%. The framework represents a flexible and efficient tool that transforms, improves and accelerates conventional process development in biomanufacturing with wide applications, including stem cell-based therapies. Copyright © 2018. Published by Elsevier Inc.

Role of gibberellins in parthenocarpic fruit development induced by the genetic system pat-3/pat-4 in tomato.

PubMed

Fos, Mariano; Proaño, Karina; Nuez, Fernando; García-Martínez, José L.

2001-04-01

The role of gibberellins (GAs) in the induction of parthenocarpic fruit-set and growth by the pat-3/pat-4 genetic system in tomato (Lycopersicon esculentum Mill.) was investigated using wild type (WT; Cuarenteno) and a near-isogenic line derived from the German line RP75/59 (the source of pat-3/pat-4 parthenocarpy). Unpollinated WT ovaries degenerated but GA3 application induced parthenocarpic fruit growth. On the contrary, parthenocarpic growth of pat-3/pat-4 fruits, which occurs in the absence of pollination and hormone treatment, was not affected by applied GA3. Unpollinated pat-3/pat-4 fruit growth was negated by paclobutrazol, an inhibitor of ent-kaurene oxidase, and this inhibitory effect was negated by GA3. The quantification of the main GAs of the early 13-hydroxylation pathway (GA1, GA8, GA19, GA20, GA29 and GA44) in unpollinated ovaries at 3 developmental stages (flower bud, FB; pre-anthesis, PR; and anthesis, AN), by gas chromatography-selected ion monitoring, showed that the concentration of most of them was higher in pat-3/pat-4 than in WT ovaries at PR and AN stages. The concentration of GA1, suggested previously to be the active GA in tomate, was 2-4 times higher. Unpollinated pat-3/pat-4 ovaries at FB, PR and AN stages also contained relatively high amounts (5-12 ng g-1) of GA3, a GA found at less than 0.5 ng g-1 in WT ovaries. It is concluded that the mutations pat-3/pat-4 may induce natural facultative parthenocarpy capacity in tomato by increasing the concentration of GA1 and GA3 in the ovaries before pollination.

Multi-modality photoacoustic tomography, ultrasound, and light sheet microscopy for volumetric tumor margin detection

NASA Astrophysics Data System (ADS)

Sangha, Gurneet S.; Hu, Bihe; Bolus, Daniel; Wang, Mei; Skidmore, Shelby J.; Sholl, Andrew B.; Brown, J. Quincy; Goergen, Craig J.

2018-02-01

Current methods for breast tumor margin detection are invasive, time consuming, and typically result in a reoperative rate of over 25%. This marks a clear clinical need to develop improved tools to intraoperatively differentiate negative versus positive tumor margins. Here, we utilize photoacoustic tomography (PAT), ultrasound (US), and inverted Selective Plane Illumination Microscopy (iSPIM) to assess breast tumor margins in eight human breast biopsies. Our PAT/US system consists of a tunable Nd:YAG laser (NT 300, EKSPLA) coupled with a 40MHz central frequency US probe (Vevo2100, FUJIFILM Visual Sonics). This system allows for the delivery of 10Hz, 5ns pulses with fluence of 40mJ/cm2 to the tissue with PAT and US axial resolutions of 125μm and 40μm, respectively. For this study, we used a linear stepper motor to acquire volumetric PAT/US images of the breast biopsies using 1100nm light to identify bloodrich "tumor" regions and 1210nm light to identify lipid-rich "healthy" regions. iSPIM (Applied Scientific Instrumentation) is an advanced microscopy technique with lateral resolution of 1.5μm and axial resolution of 7μm. We used 488nm laser excitation and acridine orange as a general comprehensive histology stain. Our results show that PAT/US can be used to identify lipid-rich regions, dense areas of arterioles and arteries, and other internal structures such as ducts. iSPIM images correlate well with histopathology slides and can verify nuclear features, cell type and density, stromal features, and microcalcifications. Together, this multimodality approach has the potential to improve tumor margin detection with a high degree of sensitivity and specificity.

Using virtual environment technology for preadapting astronauts to the novel sensory conditions of microgravity

NASA Technical Reports Server (NTRS)

Duncan, K. M.; Harm, D. L.; Crosier, W. G.; Worthington, J. W.

1993-01-01

A unique training device is being developed at the Johnson Space Center Neurosciences Laboratory to help reduce or eliminate Space Motion Sickness (SMS) and spatial orientation disturbances that occur during spaceflight. The Device for Orientation and Motion Environments Preflight Adaptation Trainer (DOME PAT) uses virtual reality technology to simulate some sensory rearrangements experienced by astronauts in microgravity. By exposing a crew member to this novel environment preflight, it is expected that he/she will become partially adapted, and thereby suffer fewer symptoms inflight. The DOME PAT is a 3.7 m spherical dome, within which a 170 by 100 deg field of view computer-generated visual database is projected. The visual database currently in use depicts the interior of a Shuttle spacelab. The trainee uses a six degree-of-freedom, isometric force hand controller to navigate through the virtual environment. Alternatively, the trainee can be 'moved' about within the virtual environment by the instructor, or can look about within the environment by wearing a restraint that controls scene motion in response to head movements. The computer system is comprised of four personal computers that provide the real time control and user interface, and two Silicon Graphics computers that generate the graphical images. The image generator computers use custom algorithms to compensate for spherical image distortion, while maintaining a video update rate of 30 Hz. The DOME PAT is the first such system known to employ virtual reality technology to reduce the untoward effects of the sensory rearrangement associated with exposure to microgravity, and it does so in a very cost-effective manner.

A regional fight against Chagas disease: lessons learned from a successful collaborative partnership.

PubMed

Salerno, Rosina; Salvatella, Roberto; Issa, Julie; Anzola, Maria Carolina

2015-01-01

To identify the intangible elements that characterize the successful effort to fight Chagas disease in the Americas, determine how they contributed to the overall success of the partnership, and learn lessons from the experience that could be applied to other programs. This study was based on the Partnership Assessment Tool (PAT) developed by the Nuffield Institute for Health ("the Institute") at the University of Leeds (London). The PAT draws heavily on scientific literature and the extensive experience of sociologists and health experts working for the Institute. The Pan American Health Organization (PAHO) modified the tool slightly to adapt it to its needs and provide a general structure for the study. The six key principles of the PAT framework were applied in the design of the research questionnaires. The findings show that a successful collaboration requires a clear objective; a good-quality pool of data; and comprehensive qualitative and quantitative knowledge of the problem, its dimensions, and its impact. The collaboration was elaborated from a common idea and a shared, quantified plan based on data gathered by independent scientists plus a strategy with explicit milestones. The clarity of purpose allowed for an improved synergy of efforts and made it possible to resolve differences in opinions and approaches. PAHO's experience with effective collaborations such as the joint initiative to fight Chagas disease provides a rich knowledge base for analysis of the advantages, limitations, and paradigms of community involvement, collaborative practices, and partnerships.

37 CFR 102.34 - Specific exemptions.

Code of Federal Regulations, 2012 CFR

2012-07-01

.../DEPT-14; (D) Attorneys and Agents Registered to Practice Before the Office—COMMERCE/PAT-TM-1; (E... OF COMMERCE ADMINISTRATION DISCLOSURE OF GOVERNMENT INFORMATION Privacy Act § 102.34 Specific... are within this exemption are: COMMERCE/PAT-TM-6, COMMERCE/PAT-TM-7, COMMERCE/PAT-TM-8, COMMERCE/PAT...

37 CFR 102.34 - Specific exemptions.

Code of Federal Regulations, 2013 CFR

2013-07-01

.../DEPT-14; (D) Attorneys and Agents Registered to Practice Before the Office—COMMERCE/PAT-TM-1; (E... OF COMMERCE ADMINISTRATION DISCLOSURE OF GOVERNMENT INFORMATION Privacy Act § 102.34 Specific... are within this exemption are: COMMERCE/PAT-TM-6, COMMERCE/PAT-TM-7, COMMERCE/PAT-TM-8, COMMERCE/PAT...

The Use of a Block Diagram Simulation Language for Rapid Model Prototyping

NASA Technical Reports Server (NTRS)

Whitlow, Johnathan E.; Engrand, Peter

1996-01-01

The research performed this summer was a continuation of work performed during the 1995 NASA/ASEE Summer Fellowship. The focus of the work was to expand previously generated predictive models for liquid oxygen (LOX) loading into the external fuel tank of the shuttle. The models which were developed using a block diagram simulation language known as VisSim, were evaluated on numerous shuttle flights and found to well in most cases. Once the models were refined and validated, the predictive methods were integrated into the existing Rockwell software propulsion advisory tool (PAT). Although time was not sufficient to completely integrate the models developed into PAT, the ability to predict flows and pressures in the orbiter section and graphically display the results was accomplished.

Process analytical technology (PAT) in insect and mammalian cell culture processes: dielectric spectroscopy and focused beam reflectance measurement (FBRM).

PubMed

Druzinec, Damir; Weiss, Katja; Elseberg, Christiane; Salzig, Denise; Kraume, Matthias; Pörtner, Ralf; Czermak, Peter

2014-01-01

Modern bioprocesses demand for a careful definition of the critical process parameters (CPPs) already during the early stages of process development in order to ensure high-quality products and satisfactory yields. In this context, online monitoring tools can be applied to recognize unfavorable changes of CPPs during the production processes and to allow for early interventions in order to prevent losses of production batches due to quality issues. Process analytical technologies such as the dielectric spectroscopy or focused beam reflectance measurement (FBRM) are possible online monitoring tools, which can be applied to monitor cell growth as well as morphological changes. Since the dielectric spectroscopy only captures cells with intact cell membranes, even information about dead cells with ruptured or leaking cell membranes can be derived. The following chapter describes the application of dielectric spectroscopy on various virus-infected and non-infected cell lines with respect to adherent as well as suspension cultures in common stirred tank reactors. The adherent mammalian cell lines Vero (African green monkey kidney cells) and hMSC-TERT (telomerase-immortalized human mesenchymal stem cells) are thereby cultured on microcarrier, which provide the required growth surface and allow the cultivation of these cells even in dynamic culture systems. In turn, the insect-derived cell lines S2 and Sf21 are used as examples for cells typically cultured in suspension. Moreover, the FBRM technology as a further monitoring tool for cell culture applications has been included in this chapter using the example of Drosophila S2 insect cells.

A Peer-Assisted Teaching Scheme to Improve Units with Critically Low Student Satisfaction: Opportunities and Challenges

ERIC Educational Resources Information Center

Carbone, Angela

2014-01-01

This paper outlines a peer-assisted teaching scheme (PATS) which was piloted in the Faculty of Information Technology at Monash University, Australia to address the low student satisfaction with the quality of information and communication technology units. Positive results from the pilot scheme led to a trial of the scheme in other disciplines.…

In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process.

PubMed

Nagy, Brigitta; Farkas, Attila; Gyürkés, Martin; Komaromy-Hiller, Szofia; Démuth, Balázs; Szabó, Bence; Nusser, Dávid; Borbás, Enikő; Marosi, György; Nagy, Zsombor Kristóf

2017-09-15

The integration of Process Analytical Technology (PAT) initiative into the continuous production of pharmaceuticals is indispensable for reliable production. The present paper reports the implementation of in-line Raman spectroscopy in a continuous blending and tableting process of a three-component model pharmaceutical system, containing caffeine as model active pharmaceutical ingredient (API), glucose as model excipient and magnesium stearate as lubricant. The real-time analysis of API content, blend homogeneity, and tablet content uniformity was performed using a Partial Least Squares (PLS) quantitative method. The in-line Raman spectroscopic monitoring showed that the continuous blender was capable of producing blends with high homogeneity, and technological malfunctions can be detected by the proposed PAT method. The Raman spectroscopy-based feedback control of the API feeder was also established, creating a 'Process Analytically Controlled Technology' (PACT), which guarantees the required API content in the produced blend. This is, to the best of the authors' knowledge, the first ever application of Raman-spectroscopy in continuous blending and the first Raman-based feedback control in the formulation technology of solid pharmaceuticals. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of a Simple Patched Conic Trajectory Code to Commercially Available Software

NASA Technical Reports Server (NTRS)

AndersonPark, Brooke M.; Wright, Henry S.

2007-01-01

Often in spaceflight proposal development, mission designers must eva luate numerous trajectories as different design factors are investiga ted. Although there are numerous commercial software packages availab le to help develop and analyze trajectories, most take a significant amount of time to develop the trajectory itself, which isn't effectiv e when working on proposals. Thus a new code, PatCon, which is both q uick and easy to use, was developed to aid mission designers to condu ct trade studies on launch and arrival times for any given target pla net. The code is able to run quick analyses, due to the incorporation of the patched conic approximation, to determine the trajectory. PatCon provides a simple but accurate approximation of the four body moti on problem that would be needed to solve any planetary trajectory. P atCon has been compared to a patched conic test case for verification, with limited validation or comparison with other COTS software. This paper describes the patched conic technique and its implementation i n PatCon. A description of the results and comparison of PatCon to ot her more evolved codes such as AGI#s Satellite Tool Kit and JAQAR As trodynamics# Swingby Calculator is provided. The results will include percent differences in values such as C3 numbers, and Vinfinity at a rrival, and other more subjective results such as the time it takes to build the simulation, and actual calculation time.

Bayesian parameter estimation in spectral quantitative photoacoustic tomography

NASA Astrophysics Data System (ADS)

Pulkkinen, Aki; Cox, Ben T.; Arridge, Simon R.; Kaipio, Jari P.; Tarvainen, Tanja

2016-03-01

Photoacoustic tomography (PAT) is an imaging technique combining strong contrast of optical imaging to high spatial resolution of ultrasound imaging. These strengths are achieved via photoacoustic effect, where a spatial absorption of light pulse is converted into a measurable propagating ultrasound wave. The method is seen as a potential tool for small animal imaging, pre-clinical investigations, study of blood vessels and vasculature, as well as for cancer imaging. The goal in PAT is to form an image of the absorbed optical energy density field via acoustic inverse problem approaches from the measured ultrasound data. Quantitative PAT (QPAT) proceeds from these images and forms quantitative estimates of the optical properties of the target. This optical inverse problem of QPAT is illposed. To alleviate the issue, spectral QPAT (SQPAT) utilizes PAT data formed at multiple optical wavelengths simultaneously with optical parameter models of tissue to form quantitative estimates of the parameters of interest. In this work, the inverse problem of SQPAT is investigated. Light propagation is modelled using the diffusion equation. Optical absorption is described with chromophore concentration weighted sum of known chromophore absorption spectra. Scattering is described by Mie scattering theory with an exponential power law. In the inverse problem, the spatially varying unknown parameters of interest are the chromophore concentrations, the Mie scattering parameters (power law factor and the exponent), and Gruneisen parameter. The inverse problem is approached with a Bayesian method. It is numerically demonstrated, that estimation of all parameters of interest is possible with the approach.

PepPat, a pattern-based oligopeptide homology search method and the identification of a novel tachykinin-like peptide.

PubMed

Jiang, Ying; Gao, Ge; Fang, Gang; Gustafson, Eric L; Laverty, Maureen; Yin, Yanbin; Zhang, Yong; Luo, Jingchu; Greene, Jonathan R; Bayne, Marvin L; Hedrick, Joseph A; Murgolo, Nicholas J

2003-05-01

PepPat, a hybrid method that combines pattern matching with similarity scoring, is described. We also report PepPat's application in the identification of a novel tachykinin-like peptide. PepPat takes as input a query peptide and a user-specified regular expression pattern within the peptide. It first performs a database pattern match and then ranks candidates on the basis of their similarity to the query peptide. PepPat calculates similarity over the pattern spanning region, enhancing PepPat's sensitivity for short query peptides. PepPat can also search for a user-specified number of occurrences of a repeated pattern within the target sequence. We illustrate PepPat's application in short peptide ligand mining. As a validation example, we report the identification of a novel tachykinin-like peptide, C14TKL-1, and show it is an NK1 (neuokinin receptor 1) agonist whose message is widely expressed in human periphery. PepPat is offered online at: http://peppat.cbi.pku.edu.cn.

Antioxidative and antigenotoxic effect of vitamin E against patulin cytotoxicity and genotoxicity in HepG2 cells.

PubMed

Ayed-Boussema, Imen; Abassi, Haila; Bouaziz, Chayma; Hlima, Wiem Ben; Ayed, Yosra; Bacha, Hassen

2013-06-01

Patulin (PAT) is a mycotoxin produced in fruits, mainly in apples, by certain species of Penicillium, Aspergillus, and Byssochlamys. It has been shown that PAT is cytotoxic, genotoxic, and mutagenic in different cell types. Several studies incriminate the oxidative stress as a mechanism of PAT-mediated toxicity. In this context, our aim was to investigate the protective role of Vitamin E (Vit E), an antioxidant agent, against PAT induced cytotoxicity and genotoxicity in cultured HepG2 cells. The obtained results showed that addition of Vit E in cells treated with PAT significantly reduce cell mortality induced by this toxin. In the same conditions, Vit E decreased the intracellular level of ROS, reduced PAT induced p53 expression, and reversed PAT induced DNA damage. In addition, Vit E prevented significantly the percentage of chromosome aberrations induced by PAT in HepG2 cells in a concentration dependant manner. These results suggest that Vit E, an exogenous antioxidant agent, plays an important role in defense against PAT-induced cytotoxicity and genotoxicity, which confirms the involvement of oxidative stress in the induction of DNA damage by PAT in HepG2 cells. Copyright © 2011 Wiley Periodicals, Inc.

Planned Experiments on the Princeton Advanced Test Stand

NASA Astrophysics Data System (ADS)

Stepanov, A.; Gilson, E. P.; Grisham, L.; Kaganovich, I.; Davidson, R. C.

2010-11-01

The Princeton Advanced Test Stand (PATS) device is an experimental facility based on the STS-100 high voltage test stand transferred from LBNL. It consists of a multicusp RF ion source, a pulsed extraction system capable of forming high-perveance 100keV ion beams, and a large six-foot-long vacuum with convenient access for beam diagnostics. This results in a flexible system for studying high perveance ion beams relevant to NDCX-I/II, including experiments on beam neutralization by ferroelectric plasma sources (FEPS) being developed at PPPL. Research on PATS will concern the basic physics of beam-plasma interactions, such as the effects of volume neutralization on beam emittance, as well as optimizing technology of the FEPS. PATS combines the advantage of an ion beam source and a large-volume plasma source in a chamber with ample access for diagnostics, resulting in a robust setup for investigating and improving relevant aspects of neutralized drift. There are also plans for running the ion source with strongly electro-negative gases such as chlorine, making it possible to extract positive or negative ion beams.

Moisture and drug solid-state monitoring during a continuous drying process using empirical and mass balance models.

PubMed

Fonteyne, Margot; Gildemyn, Delphine; Peeters, Elisabeth; Mortier, Séverine Thérèse F C; Vercruysse, Jurgen; Gernaey, Krist V; Vervaet, Chris; Remon, Jean Paul; Nopens, Ingmar; De Beer, Thomas

2014-08-01

Classically, the end point detection during fluid bed drying has been performed using indirect parameters, such as the product temperature or the humidity of the outlet drying air. This paper aims at comparing those classic methods to both in-line moisture and solid-state determination by means of Process Analytical Technology (PAT) tools (Raman and NIR spectroscopy) and a mass balance approach. The six-segmented fluid bed drying system being part of a fully continuous from-powder-to-tablet production line (ConsiGma™-25) was used for this study. A theophylline:lactose:PVP (30:67.5:2.5) blend was chosen as model formulation. For the development of the NIR-based moisture determination model, 15 calibration experiments in the fluid bed dryer were performed. Six test experiments were conducted afterwards, and the product was monitored in-line with NIR and Raman spectroscopy during drying. The results (drying endpoint and residual moisture) obtained via the NIR-based moisture determination model, the classical approach by means of indirect parameters and the mass balance model were then compared. Our conclusion is that the PAT-based method is most suited for use in a production set-up. Secondly, the different size fractions of the dried granules obtained during different experiments (fines, yield and oversized granules) were compared separately, revealing differences in both solid state of theophylline and moisture content between the different granule size fractions. Copyright © 2014 Elsevier B.V. All rights reserved.

Combined multi-modal photoacoustic tomography, optical coherence tomography (OCT) and OCT angiography system with an articulated probe for in vivo human skin structure and vasculature imaging

PubMed Central

Liu, Mengyang; Chen, Zhe; Zabihian, Behrooz; Sinz, Christoph; Zhang, Edward; Beard, Paul C.; Ginner, Laurin; Hoover, Erich; Minneman, Micheal P.; Leitgeb, Rainer A.; Kittler, Harald; Drexler, Wolfgang

2016-01-01

Cutaneous blood flow accounts for approximately 5% of cardiac output in human and plays a key role in a number of a physiological and pathological processes. We show for the first time a multi-modal photoacoustic tomography (PAT), optical coherence tomography (OCT) and OCT angiography system with an articulated probe to extract human cutaneous vasculature in vivo in various skin regions. OCT angiography supplements the microvasculature which PAT alone is unable to provide. Co-registered volumes for vessel network is further embedded in the morphologic image provided by OCT. This multi-modal system is therefore demonstrated as a valuable tool for comprehensive non-invasive human skin vasculature and morphology imaging in vivo. PMID:27699106

6-gingerol prevents patulin-induced genotoxicity in HepG2 cells.

PubMed

Yang, Guang; Zhong, Laifu; Jiang, Liping; Geng, Chengyan; Cao, Jun; Sun, Xiance; Liu, Xiaofang; Chen, Min; Ma, Yufang

2011-10-01

Patulin (PAT) is a mycotoxin produced by several Penicillium, Aspergillus and Byssochlamys species. Since PAT is a potent genotoxic compound, and PAT contamination is common in fruits and fruit products, the search for newer, better agents for protection against genotoxicity of PAT is required. In this study, the chemoprotective effect of 6-gingerol against PAT-induced genotoxicity in HepG2 cells was investigated. The comet assay and micronucleus test (MNT) were used to monitor genotoxic effects. To further elucidate the underlying mechanisms, the intracellular generation of reactive oxygen species (ROS) and level of reduced glutathione (GSH) were tested. In addition, the level of oxidative DNA damage was evaluated by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG). The results showed that 6-gingerol significantly reduced the DNA strand breaks and micronuclei formation caused by PAT. Moreover, 6-gingerol effectively suppressed PAT-induced intracellular ROS formation and 8-OHdG level. The GSH depletion induced by PAT in HepG2 cells was also attenuated by 6-gingerol pretreatment. These findings suggest that 6-gingerol has a strong protective ability against the genotoxicity caused by PAT, and the antioxidant activity of 6-gingerol may play an important part in attenuating the genotoxicity of PAT. Copyright © 2011 John Wiley & Sons, Ltd.

Detection of wheat powdery mildew by differentiating background factors using hyperspectral imaging

USDA-ARS?s Scientific Manuscript database

Accurate assessment of crop disease severities is the key for precision application of pesticides to prevent disease infestation. In-situ hyperspectral imaging technology can provide high-resolution imagery with spectra for rapid identification of crop disease and determining disease infestation pat...

Nanotechnology Characterization Laboratory Unveils New Technical Services for Drug Developers | Frederick National Laboratory for Cancer Research

Cancer.gov

FREDERICK, Md. -- Drug developers now have access to a shared analytical technology, developed and provided by the Frederick National Laboratory for Cancer Research, that helps fine-tune nanomedicine formulations and overcomes a key hurdle on the pat

The Grade 3 Provincial Achievement Tests: In Need of Revamping?

ERIC Educational Resources Information Center

Roessingh, Hetty

2012-01-01

This article advances an argument for retaining but revamping the grade 3 Provincial Achievement Tests (PATs). Alberta's demographic landscape is rapidly changing to include significant numbers of English language learners who are still in the early stages of developing English language proficiency at grade 3. Online tools are used to generate…

The role of pericardial adipose tissue in the heart of obese minipigs.

PubMed

Wang, Chia-Yu; Li, Sin-Jin; Wu, Twin-Way; Lin, Han-Jen; Chen, Jyun-Wei; Mersmann, Harry J; Ding, Shih-Torng; Chen, Ching-Yi

2018-04-23

Pericardial adipose tissue (PAT) volume is highly associated with the presence and severity of cardiometabolic diseases, but the underlying mechanism is unknown. We previously demonstrated that a high-fat diet (HFD) induced metabolic dysregulation, cardiac fibrosis and accumulation of more PAT in minipigs. This study used our obese minipig model to investigate the characteristics of PAT and omental visceral fat (VAT) induced by a HFD, and the potential link between PAT and HFD-related myocardial fibrosis. Five-month-old Lee-Sung minipigs were made obese by feeding a HFD for 6 months. The HFD induced dyslipidemia, cardiac fibrosis and more fat accumulation in the visceral and pericardial depots. The HFD changes the fatty acid composition in the adipose tissue by decreasing the portion of linoleic acid in the VAT and PAT. No arachidonic acid was detected in the VAT and PAT of control pigs, whereas it existed in the same tissues of obese pigs fed the HFD. Compared with the control pigs, elevated levels of malondialdehyde and TNFα were exhibited in the plasma and PAT of obese pigs. HFD induced greater size of adipocytes in VAT and PAT. Higher levels of GH, leptin, OPG, PDGF, resistin, SAA and TGFβ were observed in obese pig PAT compared to VAT. This study demonstrated the similarities and dissimilarities between PAT and VAT under HFD stimulus. In addition, this study suggested that alteration in PAT contributed to the myocardial damage. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

The cytoplasmic mRNA degradation factor Pat1 is required for rRNA processing

PubMed Central

Muppavarapu, Mridula; Huch, Susanne; Nissan, Tracy

2016-01-01

ABSTRACT Pat1 is a key cytoplasmic mRNA degradation factor, the loss of which severely increases mRNA half-lives. Several recent studies have shown that Pat1 can enter the nucleus and can shuttle between the nucleus and the cytoplasm. As a result, many nuclear roles have been proposed for Pat1. In this study, we analyzed four previously suggested nuclear roles of Pat1 and show that Pat1 is not required for efficient pre-mRNA splicing or pre-mRNA decay in yeast. However, lack of Pat1 results in accumulation of pre-rRNA processing intermediates. Intriguingly, we identified a novel genetic relationship between Pat1 and the rRNA decay machinery, specifically the exosome and the TRAMP complex. While the pre-rRNA processing intermediates that accumulate in the pat1 deletion mutant are, at least to some extent, recognized as aberrant by the rRNA degradation machinery, it is unlikely that these accumulations are the cause of their synthetic sick relationship. Here, we show that the dysregulation of the levels of mRNAs related to ribosome biogenesis could be the cause of the accumulation of the pre-rRNA processing intermediates. Although our results support a role for Pat1 in transcription, they nevertheless suggest that the primary cause of the dysregulated mRNA levels is most likely due to Pat1's role in mRNA decapping and mRNA degradation. PMID:26918764

The cytoplasmic mRNA degradation factor Pat1 is required for rRNA processing.

PubMed

Muppavarapu, Mridula; Huch, Susanne; Nissan, Tracy

2016-01-01

Pat1 is a key cytoplasmic mRNA degradation factor, the loss of which severely increases mRNA half-lives. Several recent studies have shown that Pat1 can enter the nucleus and can shuttle between the nucleus and the cytoplasm. As a result, many nuclear roles have been proposed for Pat1. In this study, we analyzed four previously suggested nuclear roles of Pat1 and show that Pat1 is not required for efficient pre-mRNA splicing or pre-mRNA decay in yeast. However, lack of Pat1 results in accumulation of pre-rRNA processing intermediates. Intriguingly, we identified a novel genetic relationship between Pat1 and the rRNA decay machinery, specifically the exosome and the TRAMP complex. While the pre-rRNA processing intermediates that accumulate in the pat1 deletion mutant are, at least to some extent, recognized as aberrant by the rRNA degradation machinery, it is unlikely that these accumulations are the cause of their synthetic sick relationship. Here, we show that the dysregulation of the levels of mRNAs related to ribosome biogenesis could be the cause of the accumulation of the pre-rRNA processing intermediates. Although our results support a role for Pat1 in transcription, they nevertheless suggest that the primary cause of the dysregulated mRNA levels is most likely due to Pat1's role in mRNA decapping and mRNA degradation.

Real-time imaging as an emerging process analytical technology tool for monitoring of fluid bed coating process.

PubMed

Naidu, Venkata Ramana; Deshpande, Rucha S; Syed, Moinuddin R; Wakte, Pravin S

2018-07-01

A direct imaging system (Eyecon TM ) was used as a Process Analytical Technology (PAT) tool to monitor fluid bed coating process. Eyecon TM generated real-time onscreen images, particle size and shape information of two identically manufactured laboratory-scale batches. Eyecon TM has accuracy of measuring the particle size increase of ±1 μm on particles in the size range of 50-3000 μm. Eyecon TM captured data every 2 s during the entire process. The moving average of D90 particle size values recorded by Eyecon TM were calculated for every 30 min to calculate the radial coating thickness of coated particles. After the completion of coating process, the radial coating thickness was found to be 11.3 and 9.11 μm, with a standard deviation of ±0.68 and 1.8 μm for Batch 1 and Batch 2, respectively. The coating thickness was also correlated with percent weight build-up by gel permeation chromatography (GPC) and dissolution. GPC indicated weight build-up of 10.6% and 9.27% for Batch 1 and Batch 2, respectively. In conclusion, weight build-up of 10% can also be correlated with 10 ± 2 μm increase in the coating thickness of pellets, indicating the potential applicability of real-time imaging as an endpoint determination tool for fluid bed coating process.

Quality-by-Design (QbD): An integrated process analytical technology (PAT) approach for a dynamic pharmaceutical co-precipitation process characterization and process design space development.

PubMed

Wu, Huiquan; White, Maury; Khan, Mansoor A

2011-02-28

The aim of this work was to develop an integrated process analytical technology (PAT) approach for a dynamic pharmaceutical co-precipitation process characterization and design space development. A dynamic co-precipitation process by gradually introducing water to the ternary system of naproxen-Eudragit L100-alcohol was monitored at real-time in situ via Lasentec FBRM and PVM. 3D map of count-time-chord length revealed three distinguishable process stages: incubation, transition, and steady-state. The effects of high risk process variables (slurry temperature, stirring rate, and water addition rate) on both derived co-precipitation process rates and final chord-length-distribution were evaluated systematically using a 3(3) full factorial design. Critical process variables were identified via ANOVA for both transition and steady state. General linear models (GLM) were then used for parameter estimation for each critical variable. Clear trends about effects of each critical variable during transition and steady state were found by GLM and were interpreted using fundamental process principles and Nyvlt's transfer model. Neural network models were able to link process variables with response variables at transition and steady state with R(2) of 0.88-0.98. PVM images evidenced nucleation and crystal growth. Contour plots illustrated design space via critical process variables' ranges. It demonstrated the utility of integrated PAT approach for QbD development. Published by Elsevier B.V.

Determination of patulin in fruit juices using HPLC-DAD and GC-MSD techniques.

PubMed

Moukas, Athanasios; Panagiotopoulou, Vasiliki; Markaki, Panagiota

2008-08-15

A high performance liquid chromatography with a diode-array detector (HPLC-DAD) and a gas chromatography with a mass spectrometer (GC-MSD) are described for the determination of patulin (PAT) in apple juice. The limits of detection (DL) and quantification (QL) for the HPLC-DAD and GC-MSD method were found to be (DL=0.23μgkg(-1) QL=1.2μgkg(-1)) and (DL=5.8μgkg(-1) and QL=13.8μgkg(-1)), respectively. The recovery factors for HPLC-DAD and GC-MSD were found to be 99.5% (RSD%=0.73) and 41% (RSD%=10.03), respectively. The HPLC-DAD method was used to determine the occurrence of PAT in 90 samples of fruit juices. Results revealed the presence of PAT in 100% of the samples examined. The mean values of PAT in concentrated fruit juices and in the commercial fruit juices collected from the Greek market were found to be 10.54μg PAT kg(-1) and 5.57μg PAT kg(-1) juice, respectively. The most contaminated samples were four concentrated juices ranging from 18.10μg PAT kg(-1) to 36.8μg PAT kg(-1) juice. The daily exposure to patulin for the consumers of all ages in Greece, is ranging from 0.008μg PAT kg(-1) bw to 0.1μg PAT kg(-1) bw if the daily intake of fruit juices is from 0.1 to 0.5kg. With the exception to the most contaminated sample, the daily exposure due to the samples examined, is below the provisional maximum tolerable daily intake for PAT (0.4μg PAT kg(-1) bw). Copyright © 2008 Elsevier Ltd. All rights reserved.

Rapid determination of major bioactive isoflavonoid compounds during the extraction process of kudzu (Pueraria lobata) by near-infrared transmission spectroscopy.

PubMed

Wang, Pei; Zhang, Hui; Yang, Hailong; Nie, Lei; Zang, Hengchang

2015-02-25

Near-infrared (NIR) spectroscopy has been developed into an indispensable tool for both academic research and industrial quality control in a wide field of applications. The feasibility of NIR spectroscopy to monitor the concentration of puerarin, daidzin, daidzein and total isoflavonoid (TIF) during the extraction process of kudzu (Pueraria lobata) was verified in this work. NIR spectra were collected in transmission mode and pretreated with smoothing and derivative. Partial least square regression (PLSR) was used to establish calibration models. Three different variable selection methods, including correlation coefficient method, interval partial least squares (iPLS), and successive projections algorithm (SPA) were performed and compared with models based on all of the variables. The results showed that the approach was very efficient and environmentally friendly for rapid determination of the four quality indices (QIs) in the kudzu extraction process. This method established may have the potential to be used as a process analytical technological (PAT) tool in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

Multi-parameters monitoring during traditional Chinese medicine concentration process with near infrared spectroscopy and chemometrics

NASA Astrophysics Data System (ADS)

Liu, Ronghua; Sun, Qiaofeng; Hu, Tian; Li, Lian; Nie, Lei; Wang, Jiayue; Zhou, Wanhui; Zang, Hengchang

2018-03-01

As a powerful process analytical technology (PAT) tool, near infrared (NIR) spectroscopy has been widely used in real-time monitoring. In this study, NIR spectroscopy was applied to monitor multi-parameters of traditional Chinese medicine (TCM) Shenzhiling oral liquid during the concentration process to guarantee the quality of products. Five lab scale batches were employed to construct quantitative models to determine five chemical ingredients and physical change (samples density) during concentration process. The paeoniflorin, albiflorin, liquiritin and samples density were modeled by partial least square regression (PLSR), while the content of the glycyrrhizic acid and cinnamic acid were modeled by support vector machine regression (SVMR). Standard normal variate (SNV) and/or Savitzkye-Golay (SG) smoothing with derivative methods were adopted for spectra pretreatment. Variable selection methods including correlation coefficient (CC), competitive adaptive reweighted sampling (CARS) and interval partial least squares regression (iPLS) were performed for optimizing the models. The results indicated that NIR spectroscopy was an effective tool to successfully monitoring the concentration process of Shenzhiling oral liquid.

Delivery of paclitaxel from cobalt–chromium alloy surfaces without polymeric carriers

PubMed Central

Mani, Gopinath; Macias, Celia E.; Feldman, Marc D.; Marton, Denes; Oh, Sunho; Agrawal, C. Mauli

2014-01-01

Polymer-based carriers are commonly used to deliver drugs from stents. However, adverse responses to polymer coatings have raised serious concerns. This research is focused on delivering drugs from stents without using polymers or any carriers. Paclitaxel (PAT), an anti-restenotic drug, has strong adhesion towards a variety of material surfaces. In this study, we have utilized such natural adhesion property of PAT to attach these molecules directly to cobalt–chromium (Co–Cr) alloy, an ultra-thin stent strut material. Four different groups of drug coated specimens were prepared by directly adding PAT to Co–Cr alloy surfaces: Group-A (PAT coated, unheated, and ethanol cleaned); Group-B (PAT coated, heat treated, and ethanol cleaned); Group-C (PAT coated, unheated, and not ethanol cleaned); and Group-D (PAT coated, heat treated and not ethanol cleaned). In vitro drug release of these specimens was investigated using high performance liquid chromatography. Groups A and B showed sustained PAT release for up to 56 days. A simple ethanol cleaning procedure after PAT deposition can remove the loosely bound drug crystals from the alloy surfaces and thereby allowing the remaining strongly bound drug molecules to be released at a sustained rate. The heat treatment after PAT coating further improved the stability of PAT on Co–Cr alloy and allowed the drug to be delivered at a much slower rate, especially during the initial 7 days. The specimens which were not cleaned in ethanol, Groups C and D, showed burst release. PAT coated Co–Cr alloy specimens were thoroughly characterized using scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. These techniques were collectively useful in studying the morphology, distribution, and attachment of PAT molecules on Co–Cr alloy surfaces. Thus, this study suggests the potential for delivering paclitaxel from Co–Cr alloy surfaces without using any carriers. PMID:20398928

Patulin and its dietary intake by fruit juice consumption in Iran.

PubMed

Rahimi, Ebrahim; Rezapoor Jeiran, Masoome

2015-01-01

A survey was conducted to determine levels and dietary intake of patulin (PAT) from fruit juices consumed in Iran. PAT content was determined using high performance liquid chromatography-diode array detection in 161 samples of fruit juices including apple, pineapple, pear, peach, pomegranate and white and red grape juices. Results revealed the presence of PAT in 16.1% of the samples examined, ranging from 5 to 190.7 µg/kg. Average and median PAT content in positive samples was 34.5 and 18.5 µg/kg, respectively. PAT concentration in 2.5% of the samples was higher than the maximum limit as set by European regulations for PAT in fruit products (50 µg/kg). Estimated daily intake of PAT by fruit juice was 16.4, 45.9 and 74.6 ng/kg bw/day for Iranian adults, children and babies, respectively. The results of this study showed that PAT does not seem to be a problem in fruit-based drinks commercialised in Iran, except for apple juice.

Introducing uncertainty analysis of nucleation and crystal growth models in Process Analytical Technology (PAT) system design of crystallization processes.

PubMed

Samad, Noor Asma Fazli Abdul; Sin, Gürkan; Gernaey, Krist V; Gani, Rafiqul

2013-11-01

This paper presents the application of uncertainty and sensitivity analysis as part of a systematic model-based process monitoring and control (PAT) system design framework for crystallization processes. For the uncertainty analysis, the Monte Carlo procedure is used to propagate input uncertainty, while for sensitivity analysis, global methods including the standardized regression coefficients (SRC) and Morris screening are used to identify the most significant parameters. The potassium dihydrogen phosphate (KDP) crystallization process is used as a case study, both in open-loop and closed-loop operation. In the uncertainty analysis, the impact on the predicted output of uncertain parameters related to the nucleation and the crystal growth model has been investigated for both a one- and two-dimensional crystal size distribution (CSD). The open-loop results show that the input uncertainties lead to significant uncertainties on the CSD, with appearance of a secondary peak due to secondary nucleation for both cases. The sensitivity analysis indicated that the most important parameters affecting the CSDs are nucleation order and growth order constants. In the proposed PAT system design (closed-loop), the target CSD variability was successfully reduced compared to the open-loop case, also when considering uncertainty in nucleation and crystal growth model parameters. The latter forms a strong indication of the robustness of the proposed PAT system design in achieving the target CSD and encourages its transfer to full-scale implementation. Copyright © 2013 Elsevier B.V. All rights reserved.

Improving parent-child interactions for families of children with developmental disabilities.

PubMed

Harrold, M; Lutzker, J R; Campbell, R V; Touchette, P E

1992-06-01

Child Management Training (CMT) involves compliance training with a focus on consistent use of antecedents and consequences. Planned Activities Training (PAT) focuses on teaching parents to plan for and engage in activities with their children. A multiple probe design counterbalancing PAT and CMT showed that PAT and CMT were about equally effective in improving mother-child interactions in four families with children with developmental disabilities. Responses to a social validation questionnaire indicated that parents were satisfied with the services received, and that PAT was the slightly preferred treatment. Prior research demonstrated that PAT enhanced the results of CMT. The practical advantages of PAT over CMT are discussed.

Patulin is a cultivar-dependent aggressiveness factor favouring the colonization of apples by Penicillium expansum.

PubMed

Snini, Selma P; Tannous, Joanna; Heuillard, Pauline; Bailly, Sylviane; Lippi, Yannick; Zehraoui, Enric; Barreau, Christian; Oswald, Isabelle P; Puel, Olivier

2016-08-01

The blue mould decay of apples is caused by Penicillium expansum and is associated with contamination by patulin, a worldwide regulated mycotoxin. Recently, a cluster of 15 genes (patA-patO) involved in patulin biosynthesis was identified in P. expansum. blast analysis revealed that patL encodes a Cys6 zinc finger regulatory factor. The deletion of patL caused a drastic decrease in the expression of all pat genes, leading to an absence of patulin production. Pathogenicity studies performed on 13 apple varieties indicated that the PeΔpatL strain could still infect apples, but the intensity of symptoms was weaker compared with the wild-type strain. A lower growth rate was observed in the PeΔpatL strain when this strain was grown on nine of the 13 apple varieties tested. In the complemented PeΔpatL:patL strain, the ability to grow normally in apple and the production of patulin were restored. Our results clearly demonstrate that patulin is not indispensable in the initiation of the disease, but acts as a cultivar-dependent aggressiveness factor for P. expansum. This conclusion was strengthened by the fact that the addition of patulin to apple infected by the PeΔpatL mutant restored the normal fungal colonization in apple. © 2015 BSPP AND JOHN WILEY & SONS LTD.

Molecular cloning and characterization of oocyte-specific Pat1a in Rana rugosa frogs.

PubMed

Nakamura, Yoriko; Iwasaki, Takehiro; Umei, Yosuke; Saotome, Kazuhiro; Nakajima, Yukiko; Kitahara, Shoichi; Uno, Yoshinobu; Matsuda, Yoichi; Oike, Akira; Kodama, Maho; Nakamura, Masahisa

2015-10-01

The Pat1 gene is expressed in the immature oocytes of Xenopus, and is reportedly involved in regulating the translation of maternal mRNAs required for oocyte-maturation. However, it is still unknown when Pat1a first appears in the differentiating ovary of amphibians. To address this issue, we isolated the full-length Pat1a cDNA from the frog Rana rugosa and examined its expression in the differentiating ovary of this frog. Among eight different tissues examined, the Pat1a mRNA was detectable in only the ovary. When frozen sections from the ovaries of tadpoles at various stages of development were immunostained for Vasa-a germ cell-specific protein-and Pat1a, Vasa-immunopositive signals were observed in all of the germ cells, whereas Pat1a signals were confined to the growing oocytes (50-200 μm in diameter), and absent from small germ cells (<50 μm in diameter). Forty days after testosterone injection into tadpoles to induce female-to-male sex-reversal, Pat1a-immunoreactive oocytes had disappeared completely from the sex-reversed gonad, but Vasa-positive small germ cells persisted. Thus, Pat1a would be a good marker for identifying the sexual status of the sex-reversing gonad in amphibians. In addition, fluorescence in situ hybridization analysis showed Pat1a to have an autosomal locus, suggesting that Pat1a transcription is probably regulated by a tissue-specific transcription factor in R. rugosa. © 2015 Wiley Periodicals, Inc.

Assessment of infant formula quality and composition using Vis-NIR, MIR and Raman process analytical technologies.

PubMed

Wang, Xiao; Esquerre, Carlos; Downey, Gerard; Henihan, Lisa; O'Callaghan, Donal; O'Donnell, Colm

2018-06-01

In this study, visible and near-infrared (Vis-NIR), mid-infrared (MIR) and Raman process analytical technologies were investigated for assessment of infant formula quality and compositional parameters namely preheat temperature, storage temperature, storage time, fluorescence of advanced Maillard products and soluble tryptophan (FAST) index, soluble protein, fat and surface free fat (SFF) content. PLS-DA models developed using spectral data with appropriate data pre-treatment and significant variables selected using Martens' uncertainty test had good accuracy for the discrimination of preheat temperature (92.3-100%) and storage temperature (91.7-100%). The best PLS regression models developed yielded values for the ratio of prediction error to deviation (RPD) of 3.6-6.1, 2.1-2.7, 1.7-2.9, 1.6-2.6 and 2.5-3.0 for storage time, FAST index, soluble protein, fat and SFF content prediction respectively. Vis-NIR, MIR and Raman were demonstrated to be potential PAT tools for process control and quality assurance applications in infant formula and dairy ingredient manufacture. Copyright © 2018 Elsevier B.V. All rights reserved.

76 FR 66270 - Information Collection Activity; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-26

... collection techniques on other forms of information technology. Comments may be sent to: MaryPat Daskal... form is used for generating plant construction or for the furnishing and installation of major items of..., Construction Inventory This form is used to document the final construction in connection with the closeout of...

Photoacoustic imaging of an inflammatory lesion model in the neonatal rat brain

NASA Astrophysics Data System (ADS)

Guevara, Edgar; Berti, Romain; Londono, Irène; Xie, Ningshi; Bellec, Pierre; Lesage, Frédéric; Lodygensky, G. A.

2014-09-01

Periventricular leukomalacia (PVL) is a condition that may cause significant neurodevelopmental handicap in premature newborns. It is characterized by white matter injury, associated with inflammation. This work aimed to assess the impact of inflammation on cerebral oxygen saturation (sO2) using depth-sensitive photoacoustic tomography (PAT). The aspects of PVL were reproduced in a rodent model by injection of lipopolysaccharide (LPS) into the corpus callosum. The results of this exploratory work reveal lower sO2 values in LPS group, as compared to sham controls; showing decreased values in the corpus callosum and in the left cortex, ipsilateral to the injection site. Interhemispherical connectivity was not affected by LPS injection, as shown by functional connectivity analysis. This study supports the use of PAT as a non-invasive tool to assess oxygenation values in vivo in the newborn brain.

Quantification and Reconstruction in Photoacoustic Tomography

NASA Astrophysics Data System (ADS)

Guo, Zijian

Optical absorption is closely associated with many physiological important parameters, such as the concentration and oxygen saturation of hemoglobin. Conventionally, accurate quantification in PAT requires knowledge of the optical fluence attenuation, acoustic pressure attenuation, and detection bandwidth. We circumvent this requirement by quantifying the optical absorption coefficients from the acoustic spectra of PA signals acquired at multiple optical wavelengths. We demonstrate the method using the optical-resolution photoacoustic microscopy (OR-PAM) and the acoustical-resolution photoacoustic microscopy (AR-PAM) in the optical ballistic regime and in the optical diffusive regime, respectively. The data acquisition speed in photoacoustic computed tomography (PACT) is limited by the laser repetition rate and the number of parallel ultrasound detecting channels. Reconstructing an image with fewer measurements can effectively accelerate the data acquisition and reduce the system cost. We adapted Compressed Sensing (CS) for the reconstruction in PACT. CS-based PACT was implemented as a non-linear conjugate gradient descent algorithm and tested with both phantom and in vivo experiments. Speckles have been considered ubiquitous in all scattering-based coherent imaging technologies. As a coherent imaging modality based on optical absorption, photoacoustic (PA) tomography (PAT) is generally devoid of speckles. PAT suppresses speckles by building up prominent boundary signals, via a mechanism similar to that of specular reflection. When imaging smooth boundary absorbing targets, the speckle visibility in PAT, which is defined as the ratio of the square root of the average power of speckles to that of boundaries, is inversely proportional to the square root of the absorber density. If the surfaces of the absorbing targets have uncorrelated height fluctuations, however, the boundary features may become fully developed speckles. The findings were validated by simulations and experiments. The first- and second-order statistics of PAT speckles were also studied experimentally. While the amplitude of the speckles follows a Gaussian distribution, the autocorrelation of the speckle patterns tracks that of the system point spread function.

Control of three different continuous pharmaceutical manufacturing processes: Use of soft sensors.

PubMed

Rehrl, Jakob; Karttunen, Anssi-Pekka; Nicolaï, Niels; Hörmann, Theresa; Horn, Martin; Korhonen, Ossi; Nopens, Ingmar; De Beer, Thomas; Khinast, Johannes G

2018-05-30

One major advantage of continuous pharmaceutical manufacturing over traditional batch manufacturing is the possibility of enhanced in-process control, reducing out-of-specification and waste material by appropriate discharge strategies. The decision on material discharge can be based on the measurement of active pharmaceutical ingredient (API) concentration at specific locations in the production line via process analytic technology (PAT), e.g. near-infrared (NIR) spectrometers. The implementation of the PAT instruments is associated with monetary investment and the long term operation requires techniques avoiding sensor drifts. Therefore, our paper proposes a soft sensor approach for predicting the API concentration from the feeder data. In addition, this information can be used to detect sensor drift, or serve as a replacement/supplement of specific PAT equipment. The paper presents the experimental determination of the residence time distribution of selected unit operations in three different continuous processing lines (hot melt extrusion, direct compaction, wet granulation). The mathematical models describing the soft sensor are developed and parameterized. Finally, the suggested soft sensor approach is validated on the three mentioned, different continuous processing lines, demonstrating its versatility. Copyright © 2018 Elsevier B.V. All rights reserved.

Differential expression of proton-assisted amino acid transporters (PAT[1] and PAT[2]) in tissues of neonatal pigs

USDA-ARS?s Scientific Manuscript database

The PATs have been identified as growth-regulatory nutrient sensors in Drosophila and as activators of mammalian target of rapamycin (mTOR) in mammalian cell cultures. These studies suggest that, beyond their classical function as transporters of simple amino acids (AA), the PATs act as tranceptors,...

Nanoscale Photoacoustic Tomography (nPAT) for label-free super-resolution 3D imaging of red blood cells

NASA Astrophysics Data System (ADS)

Samant, Pratik; Hernandez, Armando; Conklin, Shelby; Xiang, Liangzhong

2017-08-01

We present our results in developing nanoscale photoacoustic tomography (nPAT) for label-free super-resolution imaging in 3D. We have made progress in the development of nPAT, and have acquired our first signal. We have also performed simulations that demonstrate that nPAT is a viable imaging modality for the visualization of malaria infected red blood cells (RBCs). Our results demonstrate that nPAT is both feasible and powerful for the high resolution labelfree imaging of RBCs.

Obituary: Patrick L. Nolan (1952-2011)

NASA Astrophysics Data System (ADS)

Digel, Seth

2011-12-01

Patrick Lee Nolan died at his home in Palo Alto, California, on November 6, 2011, from complications related to a brain tumor, glioblastoma multiforme, which had been diagnosed less than five months earlier. He was born in Colusa, California, on November 18, 1952. Pat was the only child of John Henry Nolan and Carol Lee Harris Nolan. For most of his childhood they lived in Grass Valley, California, where his father was a butcher and his mother was a surgical nurse. Pat graduated from the California Institute of Technology in 1974 with a B.S. in Physics and completed a Ph.D. at the University of California at San Diego in 1982. His graduate and professional career was devoted to high-energy astronomy. His loss is being keenly felt by his friends and colleagues around the world, including the members of the Chancel Choir of the Menlo Park Presbyterian Church, of which he was a member for 25 years. At U. C. San Diego, Pat worked on construction of the Hard X-ray and Low Energy Gamma Ray Experiment for the first High Energy Astronomy Observatory mission, which was launched in 1977. His Ph.D. thesis, supervised by Prof. Laurence E. Peterson, was based on data from this instrument and addressed variability of the high-energy emission from Cygnus X-1 and other black hole binary systems in the Milky Way. After he completed his Ph.D., Pat took a National Research Council postdoctoral research position at the Naval Research Laboratory in Washington, D.C. He worked there from 1982-1984 developing spectral analysis software and studying gamma-ray bursts using the gamma-ray spectrometer on the Solar Maximum Mission satellite. A paper in Nature setting constraining limits on positron-electron annihilation radiation in the spectra of bursts marked the culmination of his efforts. Pat was hired by Prof. Robert Hofstadter at Stanford University in 1984 to work on the Energetic Gamma-Ray Experiment Telescope (EGRET). As a co-investigator for EGRET, Pat worked on its calorimeter subsystem, including calibration at the Stanford Linear Accelerator Center (SLAC), as well as on data analysis software and methods. EGRET was carried into space by the Shuttle Atlantis in 1991 as part of the Compton Gamma Ray Observatory. He led analyses of gamma-ray pulsars and other astrophysical sources, including a major study of EGRET source variability, and he was a valued resource to the many EGRET graduate students at Stanford. Members of the EGRET team regularly turned to Pat for advice on statistical analysis issues. After the launch of the Compton Observatory, Pat became a member of a small group at Stanford University and SLAC that developed and promoted a new design for a next-generation gamma-ray telescope, based on modern solid-state detectors for particle physics detectors. The concept became the Gamma-ray Large Area Space Telescope mission, which was launched by NASA in 2008 and renamed the Fermi Gamma-ray Space Telescope. The scientific collaboration for the Large Area Telescope on Fermi has grown to about 400 members from a number of countries. Pat was a recognized expert in statistics and data analysis within the collaboration and as a member of the Publication Board developed the Web and database systems for internal review of scientific publications. Pat was unassuming, widely read, and knowledgeable in many fields. These qualities together with his quiet joy in science made him a valued friend and colleague to many. At the time of his death, Pat was a Senior Research Physicist in the Hansen Experimental Physics Laboratory at Stanford University.

Effect of perineoplasm perinephric adipose tissues on migration of clear cell renal cell carcinoma cells: a potential role of WNT signaling.

PubMed

Zi, Xiaolin; Lusch, Achim; Blair, Christopher A; Okhunov, Zhamshid; Yokoyama, Noriko N; Liu, Shuman; Baker, Molly; Huynh, Victor; Landman, Jaime

2016-08-16

To investigate the cellular and molecular interactions between clear-cell renal cell carcinoma (ccRCC) and perinephric adipose tissue (PAT), perineoplasm PAT, PAT away from the neoplasm, renal sinus and subcutaneous adipose tissues were collected at the time of renal surgery for renal masses and conditioned medium (CM) was generated from 62 patients. Perineoplasm PAT CMs from 44 out of 62 (about 71%) of patients with ccRCC or benign renal diseases (e.g. oncocytomas, angiomyolipomas, multicystic kidney, interstitial fibrosis, etc.) enhanced the migration of CaKi-2 cells. Perineoplasm PAT CMs from ccRCC significantly increased migration of ACHN and CaKi-2 cells by ~8.2 and ~2.4 folds, respectively, relative to those from benign renal diseases, whereas there is no significant difference in migration between ccRCC and benign renal diseases in CMs collected from culturing PAT away from neoplasm, renal sinus and subcutaneous adipose tissues. High Fuhrman Grade was associated with increased migration of Caki-2 cells by perineoplasm PAT CMs. Perineoplasm PATs from pT3 RCCs overexpressed multiple WNTs and their CMs exhibited higher WNT/ß-catenin activity and increased the migration of Caki-2 cells compared to CMs from benign neoplasms. Addition of secreted WNT inhibitory factor-1 recombinant protein into perineoplasm PAT CMs completely blocked the cell migration. These results indicate that WNT related factors from perineoplasm PAT may promote progression of local ccRCC to locally advanced (pT3) disease by increasing ccRCC cell mobility.

Patulin reduction in apple juice by inactivated Alicyclobacillus spp.

PubMed

Yuan, Y; Wang, X; Hatab, S; Wang, Z; Wang, Y; Luo, Y; Yue, T

2014-12-01

This study aimed to investigate the reduction of patulin (PAT) in apple juice by 12 inactivated Alicyclobacillus strains. The reduction rate of PAT by each strain was determined by high-performance liquid chromatography (HPLC). The results indicated that the removal of PAT was strain specific. Alicyclobacillus acidoterrestris 92 and A. acidoterrestris 96 were the most effective ones among the 12 tested strains in the removal of PAT. Therefore, these two strains were selected to study the effects of incubation time, initial PAT concentration and bacteria powder amount on PAT removal abilities of Alicyclobacillus. The highest PAT reduction rates of 88·8 and 81·6% were achieved after 24-h incubation with initial PAT concentration of 100 μg l(-1) and bacteria powder amount of 40 g l(-1) , respectively. Moreover, it was found that the treatment by these 12 inactivated Alicyclobacillus strains had no negative effect on the quality parameters of apple juice. Similar assays were performed in supermarket apple juice, where inactivated Alicyclobacillus cells could efficiently reduce PAT content. Taken together, these data suggest the possible application of this strategy as a means to detoxify PAT-contaminated juices. Inactivated Alicyclobacillus cells can efficiently reduce patulin concentration in apple juice. It provides a theoretical foundation for recycling of Alicyclobacillus cells from spoiled apple juice to reduce the source of pollution and the cost of juice industry. This is the first report on the use of Alicyclobacillus to remove patulin from apple juice. © 2014 The Society for Applied Microbiology.

Putative DHHC-Cysteine-Rich Domain S-Acyltransferase in Plants

PubMed Central

Sun, Meihong; Liu, Shiyang; Qi, Baoxiu; Li, Xinzheng

2013-01-01

Protein S-acyltransferases (PATs) containing Asp-His-His-Cys within a Cys-rich domain (DHHC-CRD) are polytopic transmembrane proteins that are found in eukaryotic cells and mediate the S-acylation of target proteins. S-acylation is an important secondary and reversible modification that regulates the membrane association, trafficking and function of target proteins. However, little is known about the characteristics of PATs in plants. Here, we identified 804 PATs from 31 species with complete genomes. The analysis of the phylogenetic relationships suggested that all of the PATs fell into 8 groups. In addition, we analysed the phylogeny, genomic organization, chromosome localisation and expression pattern of PATs in Arabidopsis, Oryza sative, Zea mays and Glycine max. The microarray data revealed that PATs genes were expressed in different tissues and during different life stages. The preferential expression of the ZmPATs in specific tissues and the response of Zea mays to treatments with phytohormones and abiotic stress demonstrated that the PATs play roles in plant growth and development as well as in stress responses. Our data provide a useful reference for the identification and functional analysis of the members of this protein family. PMID:24155879

Issues in development, evaluation, and use of the NASA Preflight Adaptation Trainer (PAT)

NASA Technical Reports Server (NTRS)

Lane, Norman E.; Kennedy, Robert S.

1988-01-01

The Preflight Adaptation Trainer (PAT) is intended to reduce or alleviate space adaptation syndrome by providing opportunities for portions of that adaptation to occur under normal gravity conditions prior to space flight. Since the adaptation aspects of the PAT objectives involve modification not only of the behavior of the trainee, but also of sensiomotor skills which underly the behavioral generation, the defining of training objectives of the PAT utilizes four mechanisms: familiarization, demonstration, training and adaptation. These mechanisms serve as structural reference points for evaluation, drive the content and organization of the training procedures, and help to define the roles of the PAT instructors and operators. It was determined that three psychomotor properties are most critical for PAT evaluation: reliability; sensitivity; and relevance. It is cause for concern that the number of measures available to examine PAT effects exceed those that can be properly studied with the available sample sizes; special attention will be required in selection of the candidate measure set. The issues in PAT use and application within a training system context are addressed through linking the three training related mechanisms of familiarization, demonstration and training to the fourth mechanism, adaptation.

A micromachined silicon parallel acoustic delay line (PADL) array for real-time photoacoustic tomography (PAT)

NASA Astrophysics Data System (ADS)

Cho, Young Y.; Chang, Cheng-Chung; Wang, Lihong V.; Zou, Jun

2015-03-01

To achieve real-time photoacoustic tomography (PAT), massive transducer arrays and data acquisition (DAQ) electronics are needed to receive the PA signals simultaneously, which results in complex and high-cost ultrasound receiver systems. To address this issue, we have developed a new PA data acquisition approach using acoustic time delay. Optical fibers were used as parallel acoustic delay lines (PADLs) to create different time delays in multiple channels of PA signals. This makes the PA signals reach a single-element transducer at different times. As a result, they can be properly received by single-channel DAQ electronics. However, due to their small diameter and fragility, using optical fiber as acoustic delay lines poses a number of challenges in the design, construction and packaging of the PADLs, thereby limiting their performances and use in real imaging applications. In this paper, we report the development of new silicon PADLs, which are directly made from silicon wafers using advanced micromachining technologies. The silicon PADLs have very low acoustic attenuation and distortion. A linear array of 16 silicon PADLs were assembled into a handheld package with one common input port and one common output port. To demonstrate its real-time PAT capability, the silicon PADL array (with its output port interfaced with a single-element transducer) was used to receive 16 channels of PA signals simultaneously from a tissue-mimicking optical phantom sample. The reconstructed PA image matches well with the imaging target. Therefore, the silicon PADL array can provide a 16× reduction in the ultrasound DAQ channels for real-time PAT.

PAT-Based Control of Fluid Bed Coating Process Using NIR Spectroscopy to Monitor the Cellulose Coating on Pharmaceutical Pellets.

PubMed

Naidu, Venkata Ramana; Deshpande, Rucha S; Syed, Moinuddin R; Deoghare, Piyush; Singh, Dharamvir; Wakte, Pravin S

2017-08-01

Current endeavor was aimed towards monitoring percent weight build-up during functional coating process on drug-layered pellets. Near-infrared (NIR) spectroscopy is an emerging process analytical technology (PAT) tool which was employed here within quality by design (QbD) framework. Samples were withdrawn after spraying every 15-Kg cellulosic coating material during Wurster coating process of drug-loaded pellets. NIR spectra of these samples were acquired using cup spinner assembly of Thermoscientific Antaris II, followed by multivariate analysis using partial least squares (PLS) calibration model. PLS model was built by selecting various absorption regions of NIR spectra for Ethyl cellulose, drug and correlating the absorption values with actual percent weight build up determined by HPLC. The spectral regions of 8971.04 to 8250.77 cm -1 , 7515.24 to 7108.33 cm -1 , and 5257.00 to 5098.87 cm -1 were found to be specific to cellulose, where as the spectral region of 6004.45 to 5844.14 cm -1 was found to be specific to drug. The final model gave superb correlation co-efficient value of 0.9994 for calibration and 0.9984 for validation with low root mean square of error (RMSE) values of 0.147 for calibration and 0.371 for validation using 6 factors. The developed correlation between the NIR spectra and cellulose content is useful in precise at-line prediction of functional coat value and can be used for monitoring the Wurster coating process.

The parthenocarpic gene Pat-k is generated by a natural mutation of SlAGL6 affecting fruit development in tomato (Solanum lycopersicum L.).

PubMed

Takisawa, Rihito; Nakazaki, Tetsuya; Nunome, Tsukasa; Fukuoka, Hiroyuki; Kataoka, Keiko; Saito, Hiroki; Habu, Tsuyoshi; Kitajima, Akira

2018-04-27

Parthenocarpy is a desired trait in tomato because it can overcome problems with fruit setting under unfavorable environmental conditions. A parthenocarpic tomato cultivar, 'MPK-1', with a parthenocarpic gene, Pat-k, exhibits stable parthenocarpy that produces few seeds. Because 'MPK-1' produces few seeds, seedlings are propagated inefficiently via cuttings. It was reported that Pat-k is located on chromosome 1. However, the gene had not been isolated and the relationship between the parthenocarpy and low seed set in 'MPK-1' remained unclear. In this study, we isolated Pat-k to clarify the relationship between parthenocarpy and low seed set in 'MPK-1'. Using quantitative trait locus (QTL) analysis for parthenocarpy and seed production, we detected a major QTL for each trait on nearly the same region of the Pat-k locus on chromosome 1. To isolate Pat-k, we performed fine mapping using an F 4 population following the cross between a non-parthenocarpic cultivar, 'Micro-Tom' and 'MPK-1'. The results showed that Pat-k was located in the 529 kb interval between two markers, where 60 genes exist. By using data from a whole genome re-sequencing and genome sequence analysis of 'MPK-1', we could identify that the SlAGAMOUS-LIKE 6 (SlAGL6) gene of 'MPK-1' was mutated by a retrotransposon insertion. The transcript level of SlAGL6 was significantly lower in ovaries of 'MPK-1' than a non-parthenocarpic cultivar. From these results, we could conclude that Pat-k is SlAGL6, and its down-regulation in 'MPK-1' causes parthenocarpy and low seed set. In addition, we observed abnormal micropyles only in plants homozygous for the 'MPK-1' allele at the Pat-k/SlAGL6 locus. This result suggests that Pat-k/SlAGL6 is also related to ovule formation and that the low seed set in 'MPK-1' is likely caused by abnormal ovule formation through down-regulation of Pat-k/SlAGL6. Pat-k is identical to SlAGL6, and its down-regulation causes parthenocarpy and low seed set in 'MPK-1'. Moreover, down-regulation of Pat-k/SlAGL6 could cause abnormal ovule formation, leading to a reduction in the number of seeds.

Design, construction and load testing of the Pat Daly Bridge in Washington County, MO, with internal glass fiber reinforced polymers reinforcement.

DOT National Transportation Integrated Search

2013-01-01

The overarching goal of this project is to deploy and assess an innovative corrosion-free bridge construction technology for long-term : performance of new and existing bridges. The research objective of this project is to conduct a comprehensive stu...

Design, construction and load testing of the Pat Daly road bridge in Washington County, MO, with internal glass fiber reinforced polymers reinforcement.

DOT National Transportation Integrated Search

2013-01-01

The overarching goal of this project is to deploy and assess an innovative corrosion-free bridge construction technology for long-term : performance of new and existing bridges. The research objective of this project is to conduct a comprehensive stu...

Quality by design (QbD), Process Analytical Technology (PAT), and design of experiment applied to the development of multifunctional sunscreens.

PubMed

Peres, Daniela D'Almeida; Ariede, Maira Bueno; Candido, Thalita Marcilio; de Almeida, Tania Santos; Lourenço, Felipe Rebello; Consiglieri, Vladi Olga; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Baby, André Rolim

2017-02-01

Multifunctional formulations are of great importance to ensure better skin protection from harm caused by ultraviolet radiation (UV). Despite the advantages of Quality by Design and Process Analytical Technology approaches to the development and optimization of new products, we found in the literature only a few studies concerning their applications in cosmetic product industry. Thus, in this research work, we applied the QbD and PAT approaches to the development of multifunctional sunscreens containing bemotrizinol, ethylhexyl triazone, and ferulic acid. In addition, UV transmittance method was applied to assess qualitative and quantitative critical quality attributes of sunscreens using chemometrics analyses. Linear discriminant analysis allowed classifying unknown formulations, which is useful for investigation of counterfeit and adulteration. Simultaneous quantification of ethylhexyl triazone, bemotrizinol, and ferulic acid presented at the formulations was performed using PLS regression. This design allowed us to verify the compounds in isolation and in combination and to prove that the antioxidant action of ferulic acid as well as the sunscreen actions, since the presence of this component increased 90% of antioxidant activity in vitro.

Consumer physical activity tracking device ownership and use among a population-based sample of adults

PubMed Central

Macridis, Soultana; Johnston, Nora; Johnson, Steven

2018-01-01

Consumer physical activity tracking devices (PATs) have gained popularity to support individuals to be more active and less sedentary throughout the day. Wearable PATs provide real-time feedback of various fitness-related metrics such as tracking steps, sedentary time, and distance walked. The purpose of this study was to examine the prevalence and correlates of PAT ownership and use among a population-based sample of adults. A representative sample of adults ≥18 years (N = 1,215) from Alberta, Canada were recruited through random-digit dialing and responded to a questionnaire via computer-assisted telephone interviewing methods in summer 2016. Questionnaires assessed demographic and health behaviour variables, and items were designed to assess PAT ownership and usage. Logistic regression analysis (odds ratios) was used to assess correlates of PAT ownership and use. On average, participants (N = 1,215) were 53.9 (SD 16.7) years and 50.1% were female. Of the sample, 19.6% (n = 238) indicated they currently own and use a PAT. Participants who owned a PAT wore their device on average 23.2 days within the past month. Currently owning a PAT was significantly associated with being female (OR = 1.41, CI: 1.10 to 1.82), being <60 years of age (OR = 1.86, CI: 1.37 to 2.53), having at least some post secondary education (OR = 1.88, CI: 1.36 to 2.60), having a BMI ≥25 (OR = 1.52, CI: 1.16 to 1.99), and meeting physical activity guidelines (OR = 1.45, CI: 1.12 to 1.88). Similar correlates emerged for PAT use. Correlates significantly associated with PAT use and ownership included being female, being less than 60 years of age, having a post-secondary education, meeting physical activity guidelines, and being overweight/obese. This is the first study to examine characteristics of PAT ownership and use among Canadian adults. PMID:29293532

Consumer physical activity tracking device ownership and use among a population-based sample of adults.

PubMed

Macridis, Soultana; Johnston, Nora; Johnson, Steven; Vallance, Jeff K

2018-01-01

Consumer physical activity tracking devices (PATs) have gained popularity to support individuals to be more active and less sedentary throughout the day. Wearable PATs provide real-time feedback of various fitness-related metrics such as tracking steps, sedentary time, and distance walked. The purpose of this study was to examine the prevalence and correlates of PAT ownership and use among a population-based sample of adults. A representative sample of adults ≥18 years (N = 1,215) from Alberta, Canada were recruited through random-digit dialing and responded to a questionnaire via computer-assisted telephone interviewing methods in summer 2016. Questionnaires assessed demographic and health behaviour variables, and items were designed to assess PAT ownership and usage. Logistic regression analysis (odds ratios) was used to assess correlates of PAT ownership and use. On average, participants (N = 1,215) were 53.9 (SD 16.7) years and 50.1% were female. Of the sample, 19.6% (n = 238) indicated they currently own and use a PAT. Participants who owned a PAT wore their device on average 23.2 days within the past month. Currently owning a PAT was significantly associated with being female (OR = 1.41, CI: 1.10 to 1.82), being <60 years of age (OR = 1.86, CI: 1.37 to 2.53), having at least some post secondary education (OR = 1.88, CI: 1.36 to 2.60), having a BMI ≥25 (OR = 1.52, CI: 1.16 to 1.99), and meeting physical activity guidelines (OR = 1.45, CI: 1.12 to 1.88). Similar correlates emerged for PAT use. Correlates significantly associated with PAT use and ownership included being female, being less than 60 years of age, having a post-secondary education, meeting physical activity guidelines, and being overweight/obese. This is the first study to examine characteristics of PAT ownership and use among Canadian adults.

Activation of ERK mitogen-activated protein kinase in human cells by the mycotoxin patulin

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

Wu, T.-S.; Yu, F.-Y.; Su, C.-C.

2005-09-01

Patulin (PAT), a mycotoxin produced by certain species of Penicillium and Aspergillus, is often detectable in moldy fruits and their derivative products. PAT led to a concentration-dependent and time-dependent increase in phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human embryonic kidney (HEK293) cells, human peripheral blood mononuclear cells (PBMCs), and Madin-Darby canine kidney (MDCK) cells. Exposure of HEK293 cells to concentrations above 5 {mu}M PAT for 30 min induced ERK1/2 phosphorylation; activation of ERK1/2 was also observed after 24 h incubation with 0.05 {mu}M of PAT. Treatment of human PBMCs for 30 min with 30 {mu}Mmore » PAT dramatically increased the phosphorylated ERK1/2 levels. Both MEK1/2 inhibitors, U0126 and PD98059, suppressed ERK1/2 activation in either HEK293 or MDCK cells. In HEK293 cells, U0126-mediated inhibition of PAT-induced ERK1/2 phosphorylation resulted in a significant decrease in levels of DNA damage, expressed as tail moment values, in the single cell gel electrophoresis assay. Conversely, U0126 did not affect cell viability, lactate dehydrogenase release, and the DNA synthesis rate in PAT-treated cultures. Exposure of HEK293 cells for 90 min to 15 {mu}M PAT elevated the levels of early growth response gene-1 (egr-1) mRNA, but not of c-fos, fosB, and junB mRNAs. These results indicate that in human cells, PAT causes a rapid and persistent activation of ERK1/2 and this signaling pathway plays an important role in mediating PAT-induced DNA damage and egr-1 gene expression.« less

Polyamine Metabolism Is Altered in Unpollinated Parthenocarpic pat-2 Tomato Ovaries1

PubMed Central

Fos, Mariano; Proaño, Karina; Alabadí, David; Nuez, Fernando; Carbonell, Juan; García-Martínez, José L.

2003-01-01

Facultative parthenocarpy induced by the recessive mutation pat-2 in tomato (Lycopersicon esculentum Mill.) depends on gibberellins (GAs) and is associated with changes in GA content in unpollinated ovaries. Polyamines (PAs) have also been proposed to play a role in early tomato fruit development. We therefore investigated whether PAs are able to induce parthenocarpy and whether the pat-2 mutation alters the content and metabolism of PAs in unpollinated ovaries. Application of putrescine, spermidine, and spermine to wild-type unpollinated tomato ovaries (cv Madrigal [MA/wt]) induced partial parthenocarpy. Parthenocarpic growth of MA/pat-2 (a parthenocarpic near-isogenic line to MA/wt) ovaries was negated by paclobutrazol (GA biosynthesis inhibitor), and this inhibition was counteracted by spermidine. Application of α-difluoromethyl-ornithine (-Orn) and/or α-difluoromethyl-arginine (-Arg), irreversible inhibitors of the putrescine biosynthesis enzymes Orn decarboxylase (ODC) and Arg decarboxylase, respectively, prevented growth of unpollinated MA/pat-2 ovaries. α-Difluoromethyl-Arg inhibition was counteracted by putrescine and GA3, whereas that of α-difluoromethyl-Orn was counteracted by GA3 but not by putrescine or spermidine. In unpollinated MA/pat-2 ovaries, the content of free spermine was significantly higher than in MA/wt ovaries. ODC activity was higher in pat-2 ovaries than in MA/wt. Transcript levels of genes encoding ODC and spermidine synthase were also higher in MA/pat-2. All together, these results strongly suggest that the parthenocarpic ability of pat-2 mutants depends on elevated PAs levels in unpollinated mutant ovaries, which correlate with an activation of the ODC pathway, probably as a consequence of elevated GA content in unpollinated pat-2 tomato ovaries. PMID:12529543

The mycotoxin patulin reacts with DNA bases with and without previous conjugation to GSH: implication for related α,β-unsaturated carbonyl compounds?

PubMed

Pfenning, Carolin; Esch, Harald L; Fliege, Ralph; Lehmann, Leane

2016-02-01

The α,β-unsaturated carbonyl group is recognized as alert for mutagenicity, attributed to (1) its direct reaction with DNA, counteractable by glutathione (GSH), and (2) oxidative stress caused indirectly by GSH depletion. Accordingly, the α,β,γ,δ-unsaturated lactone patulin (PAT), a mycotoxin detected in fruits and products derived thereof, is known to induce gene, chromosome, and genome mutations in vitro, its mutagenicity correlating inversely with intracellular GSH levels. Thus, the reactivity of PAT against DNA bases and nucleosides in the absence and presence of GSH and glutathione S-transferases (GSTs) was investigated under cell-free conditions using HPLC mass spectrometry techniques for identification of reaction products. Adduct formation with all four nucleobases as well as with purine base nucleosides occurred even in the presence of GSH, revealing several adducts of PAT, mono- and disubstituted with nucleobases/nucleosides as well as novel GSH-PAT adducts. In addition, novel mixed GSH-PAT-nucleobase adducts were observed. These adducts exhibited a ketohexanoic acid-type structure of the PAT molecule, C6 substituted with GSH and linking C1 of PAT with nitrogens of nucleobases/nucleosides via an amide bond. Formation of GSH-PAT-adenine adducts was not prevented by GSTs, and excess of GSH needed to reduce their formation was higher than for PAT-adenine adducts. The formation of mixed GSH-DNA base adducts has not been described for PAT or any other α,β-unsaturated carbonyl before, although the reaction mechanism seems to be applicable to a variety of α,β-unsaturated carbonyls occurring in food and in the environment.

Validation of Watch-PAT-200 Against Polysomnography During Pregnancy

PubMed Central

O'Brien, Louise M.; Bullough, Alexandra S.; Shelgikar, Anita V.; Chames, Mark C.; Armitage, Roseanne; Chervin, Ronald D.

2012-01-01

Study Objectives: To determine the relationships between key variables obtained from ambulatory polysomnography (PSG) and the wrist-worn Watch-PAT 200 device in pregnant women. Methods: In this prospective cohort study, women in their third trimester of pregnancy underwent full overnight home PSG using the 22-channel MediPalm system and the Watch-PAT 200 device. PSGs were scored by a blinded, experienced technologist using AASM 2007 criteria; the Watch-PAT was scored automatically by the manufacturer's proprietary software. Results: A total of 31 pregnant women were studied. Mean age was 30.2 ± 7.1 years; mean gestational age was 33.4 ± 3.0 weeks; mean BMI was 31.9 ± 8.1 kg/m2; 39% of women were nulliparous. Key variables generated by PSG and Watch-PAT correlated well over a wide range, including the apnea-hypopnea index (AHI, r = 0.76, p < 0.001); respiratory disturbance index (RDI, r = 0.68, p < 0.001), mean oxygen saturation (r = 0.94, p < 0.001), and minimum oxygen saturation (r = 0.88, p < 0.001). The area under the curve for AHI ≥ 5 and RDI ≥ 10 were 0.96 and 0.94, respectively. Association between stage 3 sleep on PSG and deep sleep on Watch-PAT was poor. Watch-PAT tended to overscore RDI, particularly as severity increased. Conclusions: Among pregnant women, Watch-PAT demonstrates excellent sensitivity and specificity for identification of obstructive sleep apnea, defined as AHI ≥ 5 on full PSG. Watch-PAT may overestimate RDI somewhat, especially at high RDI values. Citation: O'Brien LM; Bullough AS; Shelgikar AV; Chames MC; Armitage R; Chervin RD. Validation of Watch-Pat-200 against polysomnography during pregnancy. J Clin Sleep Med 2012;8(3):287-294. PMID:22701386

Consequences of Lipid Droplet Coat Protein Downregulation in Liver Cells

PubMed Central

Bell, Ming; Wang, Hong; Chen, Hui; McLenithan, John C.; Gong, Da-Wei; Yang, Rong-Zee; Yu, Daozhan; Fried, Susan K.; Quon, Michael J.; Londos, Constantine; Sztalryd, Carole

2008-01-01

OBJECTIVE—Accumulation of intracellular lipid droplets (LDs) in non-adipose tissues is recognized as a strong prognostic factor for the development of insulin resistance in obesity. LDs are coated with perilipin, adipose differentiation–related protein, tail interacting protein of 47 kd (PAT) proteins that are thought to regulate LD turnover by modulating lipolysis. Our hypothesis is that PAT proteins modulate LD metabolism and therefore insulin resistance. RESEARCH DESIGN AND METHODS—We used a cell culture model (murine AML12 loaded with oleic acid) and small interfering RNA to directly assess the impact of PAT proteins on LD accumulation, lipid metabolism, and insulin action. PAT proteins associated with excess fat deposited in livers of diet-induced obese (DIO) mice were also measured. RESULTS—Cells lacking PAT proteins exhibited a dramatic increase in LD size and a decrease in LD number. Further, the lipolytic rate increased by ∼2- to 2.5-fold in association with increased adipose triglyceride lipase (ATGL) at the LD surface. Downregulation of PAT proteins also produced insulin resistance, as indicated by decreased insulin stimulation of Akt phosphorylation (P < 0.001). Phosphoinositide-dependent kinase-1 and phosphoinositide 3-kinase decreased, and insulin receptor substrate-1 307 phosphorylation increased. Increased lipids in DIO mice livers were accompanied by changes in PAT composition but also increased ATGL, suggesting a relative PAT deficiency. CONCLUSIONS—These data establish an important role for PAT proteins as surfactant at the LD surface, packaging lipids in smaller units and restricting access of lipases and thus preventing insulin resistance. We suggest that a deficiency of PAT proteins relative to the quantity of ectopic fat could contribute to cellular dysfunction in obesity and type 2 diabetes. PMID:18487449

A Scintillation Counter System Design To Detect Antiproton Annihilation using the High Performance Antiproton Trap(HiPAT)

NASA Technical Reports Server (NTRS)

Martin, James J.; Lewis, Raymond A.; Stanojev, Boris

2003-01-01

The High Performance Antiproton Trap (HiPAT), a system designed to hold up to l0(exp 12) charge particles with a storage half-life of approximately 18 days, is a tool to support basic antimatter research. NASA's interest stems from the energy density represented by the annihilation of matter with antimatter, 10(exp 2)MJ/g. The HiPAT is configured with a Penning-Malmberg style electromagnetic confinement region with field strengths up to 4 Tesla, and 20kV. To date a series of normal matter experiments, using positive and negative ions, have been performed evaluating the designs performance prior to operations with antiprotons. The primary methods of detecting and monitoring stored normal matter ions and antiprotons within the trap includes a destructive extraction technique that makes use of a micro channel plate (MCP) device and a non-destractive radio frequency scheme tuned to key particle frequencies. However, an independent means of detecting stored antiprotons is possible by making use of the actual annihilation products as a unique indicator. The immediate yield of the annihilation event includes photons and pie mesons, emanating spherically from the point of annihilation. To "count" these events, a hardware system of scintillators, discriminators, coincident meters and multi channel scalars (MCS) have been configured to surround much of the HiPAT. Signal coincidence with voting logic is an essential part of this system, necessary to weed out the single cosmic ray events from the multi-particle annihilation shower. This system can be operated in a variety of modes accommodating various conditions. The first is a low-speed sampling interval that monitors the background loss or "evaporation" rate of antiprotons held in the trap during long storage periods; provides an independent method of validating particle lifetimes. The second is a high-speed sample rate accumulating information on a microseconds time-scale; useful when trapped antiparticles are extracted against a target, providing an indication of quantity. This paper details the layout of this system, setup of the hardware components around HiPAT, and applicable checkouts using normal matter radioactive sources.

Photoacoustic Imaging of Epilepsy

DTIC Science & Technology

2014-04-01

with the skin and skull intact. MCA, middle cerebral artery; RH, right hemispheres; LH, left hemispheres; LOB, left olfactory bulbs; ROB, Right...moving rat brain with skin and skull intact. (D) Open-skull photograph of the rat cortex surface after the PAT experiments The PAT detecting...22D shows a typical non-invasive PAT image obtained with the miniature PAT imaging system of a freely moving rat brain with skin and skull intact. Fig

Tutorial on photoacoustic tomography

NASA Astrophysics Data System (ADS)

Zhou, Yong; Yao, Junjie; Wang, Lihong V.

2016-06-01

Photoacoustic tomography (PAT) has become one of the fastest growing fields in biomedical optics. Unlike pure optical imaging, such as confocal microscopy and two-photon microscopy, PAT employs acoustic detection to image optical absorption contrast with high-resolution deep into scattering tissue. So far, PAT has been widely used for multiscale anatomical, functional, and molecular imaging of biological tissues. We focus on PAT's basic principles, major implementations, imaging contrasts, and recent applications.

Impact of preoperative antithrombotic therapy on blood management after implantation of primary total knee arthroplasty

PubMed Central

Leitner, Lukas; Musser, Ewald; Kastner, Norbert; Friesenbichler, Jörg; Hirzberger, Daniela; Radl, Roman; Leithner, Andreas; Sadoghi, Patrick

2016-01-01

Red blood cell concentrates (RCC) substitution after total knee arthroplasty (TKA) is correlated with multifold of complications and an independent predictor for higher postoperative mortality. TKA is mainly performed in elderly patients with pre-existing polymorbidity, often requiring permanent preoperative antithrombotic therapy (PAT). The aim of this retrospective analysis was to investigate the impact of demand for PAT on inpatient blood management in patients undergoing TKA. In this study 200 patients were retrospectively evaluated after TKA for differences between PAT and non-PAT regarding demographic parameters, preoperative ASA score > 2, duration of operation, pre-, and intraoperative hemoglobin level, and postoperative parameters including amount of wound drainage, RCC requirement, and inpatient time. In a multivariate logistic regression analysis the independent influences of PAT, demographic parameters, ASA score > 2, and duration of the operation on RCC demand following TKA were analyzed. Patients with PAT were significantly older, more often had an ASA > 2 at surgery, needed a higher number of RCCs units and more frequently and had lower perioperative hemoglobin levels. Multivariate logistic regression revealed PAT was an independent predictor for RCC requirement. PAT patients are more likely to require RCC following TKA and should be accurately monitored with respect to postoperative blood loss. PMID:27488941

Impact of preoperative antithrombotic therapy on blood management after implantation of primary total knee arthroplasty.

PubMed

Leitner, Lukas; Musser, Ewald; Kastner, Norbert; Friesenbichler, Jörg; Hirzberger, Daniela; Radl, Roman; Leithner, Andreas; Sadoghi, Patrick

2016-08-04

Red blood cell concentrates (RCC) substitution after total knee arthroplasty (TKA) is correlated with multifold of complications and an independent predictor for higher postoperative mortality. TKA is mainly performed in elderly patients with pre-existing polymorbidity, often requiring permanent preoperative antithrombotic therapy (PAT). The aim of this retrospective analysis was to investigate the impact of demand for PAT on inpatient blood management in patients undergoing TKA. In this study 200 patients were retrospectively evaluated after TKA for differences between PAT and non-PAT regarding demographic parameters, preoperative ASA score > 2, duration of operation, pre-, and intraoperative hemoglobin level, and postoperative parameters including amount of wound drainage, RCC requirement, and inpatient time. In a multivariate logistic regression analysis the independent influences of PAT, demographic parameters, ASA score > 2, and duration of the operation on RCC demand following TKA were analyzed. Patients with PAT were significantly older, more often had an ASA > 2 at surgery, needed a higher number of RCCs units and more frequently and had lower perioperative hemoglobin levels. Multivariate logistic regression revealed PAT was an independent predictor for RCC requirement. PAT patients are more likely to require RCC following TKA and should be accurately monitored with respect to postoperative blood loss.

Mycoflora assessment, growth and toxigenic features of patulin-producers in kiwifruit in China.

PubMed

Wang, Yuan; Feng, Kewei; Liu, Bin; Zhang, Zhiwei; Wei, Jianping; Yuan, Yahong; Yue, Tianli

2018-05-01

Fungal development in agricultural products may cause mycotoxin contamination, which is a significant threat to food safety. Patulin (PAT) and PAT-producer contamination has been established as a worldwide problem. The present study aimed to investigate the mycoflora and PAT-producers present in kiwifruits and environmental samples collected from orchards and processing plants in Shaanxi Province, China. Variations in mycoflora were observed in different samples, with penicillia and aspergilli as the predominant genera. Approximately 42.86% of dropped fruits were contaminated with PAT-producers, which harbored the 6-methylsalicylic acid synthase and the isoepoxydon dehydrogenase genes that are involved in PAT biosynthesis. The growth of Penicillium expansum, Penicillium griseofulvum and Penicillium paneum in kiwi puree agar (KPA) medium and kiwi juice well fitted the modified Gompertz and Baranyi and Roberts models (R 2 ≥ 0.95). A significant positive correlation between colony diameter and PAT content in KPA medium of P. expansum and P. griseofulvum was observed (P < 0.05). The present study analyzed the mycofloral composition and the potential risk for PAT and PAT-producer contamination in kiwifruit, which may be utilized in the establishment of proper management practices in the kiwifruit industry. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Physics and Advanced Technologies 2003 Annual Report

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

Hazi, A; Sketchley, J

2005-01-20

The Physics and Advanced Technologies (PAT) Directorate overcame significant challenges in 2003 to deliver a wealth of scientific and programmatic milestones, and move toward closer alignment with programs at Lawrence Livermore National Laboratory. We acted aggressively in enabling the PAT Directorate to contribute to future, growing Lawrence Livermore missions in homeland security and at the National Ignition Facility (NIF). We made heavy investments to bring new capabilities to the Laboratory, to initiate collaborations with major Laboratory programs, and to align with future Laboratory directions. Consistent with our mission, we sought to ensure that Livermore programs have access to the bestmore » science and technology, today and tomorrow. For example, in a move aimed at revitalizing the Laboratory's expertise in nuclear and radiation detection, we brought the talented Measurement Sciences Group to Livermore from Lawrence Berkeley National Laboratory, after its mission there had diminished. The transfer to our I Division entailed significant investment by PAT in equipment and infrastructure required by the group. In addition, the move occurred at a time when homeland security funding was expected, but not yet available. By the end of the year, though, the group was making crucial contributions to the radiation detection program at Livermore, and nearly every member was fully engaged in programmatic activities. Our V Division made a move of a different sort, relocating en masse from Building 121 to the NIF complex. This move was designed to enhance interaction and collaboration among high-energy-density experimental scientists at the Laboratory, a goal that is essential to the effective use of NIF in the future. Since then, V Division has become increasingly integrated with NIF activities. Division scientists are heavily involved in diagnostic development and fielding and are poised to perform equation-of-state and high-temperature hohlraum experiments in 2004 as part of the NIF Early Light program.« less

4-D photoacoustic tomography.

PubMed

Xiang, Liangzhong; Wang, Bo; Ji, Lijun; Jiang, Huabei

2013-01-01

Photoacoustic tomography (PAT) offers three-dimensional (3D) structural and functional imaging of living biological tissue with label-free, optical absorption contrast. These attributes lend PAT imaging to a wide variety of applications in clinical medicine and preclinical research. Despite advances in live animal imaging with PAT, there is still a need for 3D imaging at centimeter depths in real-time. We report the development of four dimensional (4D) PAT, which integrates time resolutions with 3D spatial resolution, obtained using spherical arrays of ultrasonic detectors. The 4D PAT technique generates motion pictures of imaged tissue, enabling real time tracking of dynamic physiological and pathological processes at hundred micrometer-millisecond resolutions. The 4D PAT technique is used here to image needle-based drug delivery and pharmacokinetics. We also use this technique to monitor 1) fast hemodynamic changes during inter-ictal epileptic seizures and 2) temperature variations during tumor thermal therapy.

Discovery and characterization of inhibitors of human palmitoyl acyltransferases.

PubMed

Ducker, Charles E; Griffel, Lindsay K; Smith, Ryan A; Keller, Staci N; Zhuang, Yan; Xia, Zuping; Diller, John D; Smith, Charles D

2006-07-01

The covalent attachment of palmitate to specific proteins by the action of palmitoyl acyltransferases (PAT) plays critical roles in the biological activities of several oncoproteins. Two PAT activities are expressed by human cells: type 1 PATs that modify the farnesyl-dependent palmitoylation motif found in H- and N-Ras, and type 2 PATs that modify the myristoyl-dependent palmitoylation motif found in the Src family of tyrosine kinases. We have previously shown that the type 1 PAT HIP14 causes cellular transformation. In the current study, we show that mRNA encoding HIP14 is up-regulated in a number of types of human tumors. To assess the potential of HIP14 and other PATs as targets for new anticancer drugs, we developed three cell-based assays suitable for high-throughput screening to identify inhibitors of these enzymes. Using these screens, five chemotypes, with activity toward either type 1 or type 2 PAT activity, were identified. The activity of the hits were confirmed using assays that quantify the in vitro inhibition of PAT activity, as well as a cell-based assay that determines the abilities of the compounds to prevent the localization of palmitoylated green fluorescent proteins to the plasma membrane. Representative compounds from each chemotype showed broad antiproliferative activity toward a panel of human tumor cell lines and inhibited the growth of tumors in vivo. Together, these data show that PATs, and HIP14 in particular, are interesting new targets for anticancer compounds, and that small molecules with such activity can be identified by high-throughput screening.

Discovery and characterization of inhibitors of human palmitoyl acyltransferases

PubMed Central

Ducker, Charles E.; Griffel, Lindsay K.; Smith, Ryan A.; Keller, Staci N.; Zhuang, Yan; Xia, Zuping; Diller, John D.; Smith, Charles D.

2010-01-01

The covalent attachment of palmitate to specific proteins by the action of palmitoyl acyltransferases (PAT) plays critical roles in the biological activities of several oncoproteins. Two PAT activities are expressed by human cells: type 1 PATs that modify the farnesyl-dependent palmitoylation motif found in H- and N-Ras, and type 2 PATs that modify the myristoyl-dependent palmitoylation motif found in the Src family of tyrosine kinases. We have previously shown that the type 1 PAT HIP14 causes cellular transformation. In the current study, we show that mRNA encoding HIP14 is up-regulated in a number of types of human tumors. To assess the potential of HIP14 and other PATs as targets for new anticancer drugs, we developed three cell-based assays suitable for high-throughput screening to identify inhibitors of these enzymes. Using these screens, five chemotypes, with activity toward either type 1 or type 2 PAT activity, were identified. The activity of the hits were confirmed using assays that quantify the in vitro inhibition of PAT activity, as well as a cell-based assay that determines the abilities of the compounds to prevent the localization of palmitoylated green fluorescent proteins to the plasma membrane. Representative compounds from each chemotype showed broad antiproliferative activity toward a panel of human tumor cell lines and inhibited the growth of tumors in vivo. Together, these data show that PATs, and HIP14 in particular, are interesting new targets for anticancer compounds, and that small molecules with such activity can be identified by high-throughput screening. PMID:16891450

Prevalence of protective antibody titers for canine distemper virus and canine parvovirus in dogs entering a Florida animal shelter.

PubMed

Lechner, Elizabeth S; Crawford, P Cynda; Levy, Julie K; Edinboro, Charlotte H; Dubovi, Edward J; Caligiuri, Randy

2010-06-15

To determine the proportion of dogs entering an animal shelter with protective antibody titers (PATs) for canine distemper virus (CDV) and canine parvovirus (CPV) and identify factors associated with having a PAT. Cross-sectional study. 431 dogs admitted to an open-admission municipal animal shelter in north central Florida with a history of infectious disease outbreaks. Blood was collected from dogs on the day of admission to the shelter. Antibody titers for CDV and CPV were measured by virus neutralization and hemagglutination inhibition, respectively. Age, sex, neuter status, address of origin, source (stray or previously owned), health status (healthy or not healthy), and outcome (adoption, euthanasia, or reclaimed by owner) data were also collected. Overall, 64.5% (278/431) of dogs had insufficient titers for antibodies against CDV, CPV, or both. A total of 153 (35.5%) dogs had PATs for both CDV and CPV, 33 (7.7%) had PATs for CDV but not CPV, 136 (31.5%) had PATs for CPV but not CDV, and 109 (25.3%) did not have PATs for either virus. Older dogs were more likely to have PATs for CDV and CPV. Neutered dogs were more likely to have PATs for CDV. Factors not associated with having a PAT included source, health status, and type of community from which the dog originated. Most dogs had insufficient antibody titers for CDV, CPV, or both at the time of admission to the animal shelter. Findings support current guidelines recommending vaccination of all dogs immediately upon admission to shelters, regardless of source or physical condition.

GeoPAT: A toolbox for pattern-based information retrieval from large geospatial databases

NASA Astrophysics Data System (ADS)

Jasiewicz, Jarosław; Netzel, Paweł; Stepinski, Tomasz

2015-07-01

Geospatial Pattern Analysis Toolbox (GeoPAT) is a collection of GRASS GIS modules for carrying out pattern-based geospatial analysis of images and other spatial datasets. The need for pattern-based analysis arises when images/rasters contain rich spatial information either because of their very high resolution or their very large spatial extent. Elementary units of pattern-based analysis are scenes - patches of surface consisting of a complex arrangement of individual pixels (patterns). GeoPAT modules implement popular GIS algorithms, such as query, overlay, and segmentation, to operate on the grid of scenes. To achieve these capabilities GeoPAT includes a library of scene signatures - compact numerical descriptors of patterns, and a library of distance functions - providing numerical means of assessing dissimilarity between scenes. Ancillary GeoPAT modules use these functions to construct a grid of scenes or to assign signatures to individual scenes having regular or irregular geometries. Thus GeoPAT combines knowledge retrieval from patterns with mapping tasks within a single integrated GIS environment. GeoPAT is designed to identify and analyze complex, highly generalized classes in spatial datasets. Examples include distinguishing between different styles of urban settlements using VHR images, delineating different landscape types in land cover maps, and mapping physiographic units from DEM. The concept of pattern-based spatial analysis is explained and the roles of all modules and functions are described. A case study example pertaining to delineation of landscape types in a subregion of NLCD is given. Performance evaluation is included to highlight GeoPAT's applicability to very large datasets. The GeoPAT toolbox is available for download from

Photoacoustic tomography: principles and advances

PubMed Central

Xia, Jun; Yao, Junjie; Wang, Lihong V.

2014-01-01

Photoacoustic tomography (PAT) is an emerging imaging modality that shows great potential for preclinical research and clinical practice. As a hybrid technique, PAT is based on the acoustic detection of optical absorption from either endogenous chromophores, such as oxy-hemoglobin and deoxy-hemoglobin, or exogenous contrast agents, such as organic dyes and nanoparticles. Because ultrasound scatters much less than light in tissue, PAT generates high-resolution images in both the optical ballistic and diffusive regimes. Over the past decade, the photoacoustic technique has been evolving rapidly, leading to a variety of exciting discoveries and applications. This review covers the basic principles of PAT and its different implementations. Strengths of PAT are highlighted, along with the most recent imaging results. PMID:25642127

Capabilities-Based Planning for Energy Security at Department of Defense Installations

DTIC Science & Technology

2013-01-01

Support Services—The ability to provide assis- tance for payload and launch vehicles including safety, reception , staging, integration, movement to the...pubs/technical_reports/TR1249.html Davis, Paul K., and Paul Dreyer, RAND’s Portfolio Analysis Tool (PAT): Theory , Methods, and Reference Manual, Santa...Steven C. Bankes, and Michael Egner, Enhancing Strategic Planning with Massive Scenario Generation: Theory and Experiments, Santa Monica, Calif

Application of droplet digital PCR for quantitative detection of Spiroplasma citri in comparison with real time PCR

USDA-ARS?s Scientific Manuscript database

Droplet digital Polymerase chain reaction (ddPCR) is a unique approach to measure the absolute copy number of nucleic acid targets without the need of external standards. It is a promising DNA quantification technology for medical diagnostics but there are only a few reports of its use for plant pat...

Inter-species protein trafficking endows dodder (Cuscuta pentagona) with a host-specific herbicide-tolerant trait.

PubMed

Jiang, Linjian; Qu, Feng; Li, Zhaohu; Doohan, Douglas

2013-06-01

· Besides photosynthates, dodder (Cuscuta spp.) acquires phloem-mobile proteins from host; however, whether this could mediate inter-species phenotype transfer was not demonstrated. Specifically, we test whether phosphinothricin acetyl transferase (PAT) that confers host plant glufosinate herbicide tolerance traffics and functions inter-specifically. · Dodder tendrils excised from hosts can grow in vitro for weeks or resume in vivo by parasitizing new hosts. The level of PAT in in vivo and in vitro dodder tendrils was quantified by enzyme-linked immunosorbent assay. The glufosinate sensitivity was examined by dipping the distal end of in vivo and in vitro tendrils, growing on or excised from LibertyLink (LL; PAT-transgenic and glufosinate tolerant) and conventional (CN; glufosinate sensitive) soybean hosts, into glufosinate solutions for 5 s. After in vitro tendrils excised from LL hosts reparasitized new CN and LL hosts, the PAT level and the glufosinate sensitivity were also examined. · When growing on LL host, dodder tolerated glufosinate and contained PAT at a level of 0.3% of that encountered in LL soybean leaf. After PAT was largely degraded in dodders, they became glufosinate sensitive. PAT mRNA was not detected by reverse transcription PCR in dodders. · In conclusion, the results indicated that PAT inter-species trafficking confers dodder glufosinate tolerance. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Mutagenesis Analysis Reveals Distinct Amino Acids of the Human Serotonin 5-HT2C Receptor Underlying the Pharmacology of Distinct Ligands.

PubMed

Liu, Yue; Canal, Clinton E; Cordova-Sintjago, Tania C; Zhu, Wanying; Booth, Raymond G

2017-01-18

While exploring the structure-activity relationship of 4-phenyl-2-dimethylaminotetralins (PATs) at serotonin 5-HT 2C receptors, we discovered that relatively minor modification of PAT chemistry impacts function at 5-HT 2C receptors. In HEK293 cells expressing human 5-HT 2C-INI receptors, for example, (-)-trans-3'-Br-PAT and (-)-trans-3'-Cl-PAT are agonists regarding Gα q -inositol phosphate signaling, whereas (-)-trans-3'-CF 3 -PAT is an inverse agonist. To investigate the ligand-receptor interactions that govern this change in function, we performed site-directed mutagenesis of 14 amino acids of the 5-HT 2C receptor based on molecular modeling and reported G protein-coupled receptor crystal structures, followed by molecular pharmacology studies. We found that S3.36, T3.37, and F5.47 in the orthosteric binding pocket are critical for affinity (K i ) of all PATs tested, we also found that F6.44, M6.47, C7.45, and S7.46 are primarily involved in regulating EC/IC 50 functional potencies of PATs. We discovered that when residue S5.43, N6.55, or both are mutated to alanine, (-)-trans-3'-CF 3 -PAT switches from inverse agonist to agonist function, and when N6.55 is mutated to leucine, (-)-trans-3'-Br-PAT switches from agonist to inverse agonist function. Notably, most point-mutations that affected PAT pharmacology did not significantly alter affinity (K D ) of the antagonist radioligand [ 3 H]mesulergine, but every mutation tested negatively impacted serotonin binding. Also, amino acid mutations differentially affected the pharmacology of other commercially available 5-HT 2C ligands tested. Collectively, the data show that functional outcomes shared by different ligands are mediated by different amino acids and that some 5-HT 2C receptor residues important for pharmacology of one ligand are not necessarily important for another ligand.

Recombinant human antithrombin expressed in the milk of non-transgenic goats exhibits high efficiency on rat DIC model.

PubMed

Yang, Hai; Li, Qing-Wang; Han, Zeng-Sheng; Hu, Jian-Hong; Li, Wen-Ye; Liu, Zhi-Bin

2009-11-01

Plasma-derived antithrombin (pAT) is often used for the treatments of disseminated intravascular coagulation (DIC) patients. In this paper, the recombinant adenovirus vector encoding human antithrombin (AT) cDNA was constructed and directly infused into the mammary gland of two goats. The recombinant human antithrombin (rhAT) was purified by heparin affinity chromatography from the goat milk, and then used in the treatment of thirty lipopolysaccharide (LPS) induced DIC rats. A high expression level of rhAT up to 2.8 g/l was obtained in the milk of goats. After purification, the recovery rate and the purity of the rhAT were up to 54.7 +/- 3.2% and 96.2 +/- 2.7%, respectively. In blood of the DIC rat model treated with rhAT, the levels of antithrombin and thrombin-antithrombin (TAT) were augmented significantly; meanwhile the consumption of fibrinogen and platelet was reduced significantly, and the increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentration was restrained modest and non-significant. For the above DIC indexes, there were no differences between pAT and rhAT (P > 0.05). Our results demonstrated that the way we established is a pragmatic tool for large-scale production of rhAT, and the rhAT produced with this method has potential as a substitute for pAT in the therapy of DIC patients.

Feelings of powerlessness in patients with venous leg ulcers.

PubMed

Salomé, G M; Openheimer, D G; de Almeida, S A; Bueno, M L G B; Dutra, R A A; Ferreira, L M

2013-11-01

To assess feelings of powerlessness in patients with venous leg ulcers. An exploratory, descriptive, analytic, cross-sectional study was conducted at the Plastic Surgery Outpatient Clinic of the São Paulo Hospital (HSP) and at the Outpatient Wound-Care Clinic of the Sorocaba Hospital Complex (CHS), Brazil, from May 2010 to April 2012. Sixty patients with venous leg ulcers (VLUs), of both sexes, aged greater than or equal to 18 years, from the two outpatient wound-care clinics were selected to participate in the study. All participants responded to the Powerlessness Assessment Tool (PAT) for adult patients. Statistical analysis was performed using the Chi-square test, Mann-Whitney U test and Kruskal-Wallis test at a significance level of 5% (p<0.05). Forty-four (73%) patients were women and 38 (63%) were aged 61-70 years. Eight (13%) patients were alcoholics and 46 (77%) were smokers. Thirty-two (53%) patients had a VLU for more than 10 years; the ulcer area ranged from 11-20 cm2 in 19 (32%) patients and was >30 cm2 in 18 (30%) patients. Mean total PAT score was 47.83 ± 7.99 and ranged from 51-60 for 31 (52%) patients and from 41-50 for 19 (32%) patients. Most patients with venous leg ulcers reported high PAT scores, revealing the presence of strong feelings of powerlessness. The authors have no conflicts of interest to declare.

Type studies of resupinate hydnaceous Hymenomycetes described by Patouillard

Treesearch

Karen K. Nakasone

2003-01-01

Type specimens of fourteen resupinate or pileate, hydnaceous Basidiomycotina, Aphyllophorales) species described by Patouillard were studied. The species are from Ecuador, Guadeloupe, Java, Madagascar, Tunisia, Venezuela, and Vietnam. New combinations Beenakia hololeuca (Pat.) Nakasone, Hyphodontia ochroflava (Pat.) Nakasone, Phlebia citrea (Pat.) Nakasone,...

Comparison of temporal to pulmonary artery temperature in febrile patients.

PubMed

Furlong, Donna; Carroll, Diane L; Finn, Cynthia; Gay, Diane; Gryglik, Christine; Donahue, Vivian

2015-01-01

As a routine part of clinical care, temperature measurement is a key indicator of illness. With the criterion standard of temperature measurement from the pulmonary artery catheter thermistor (PAT), which insertion of PAT carries significant risk to the patient, a noninvasive method that is accurate and precise is needed. The purpose of this study was to measure the precision and accuracy of 2 commonly used methods of collecting body temperature: PAT considered the criterion standard and the temporal artery thermometer (TAT) in those patients with a temperature greater than 100.4°F. This is a repeated-measures design with each patient with a PAT in the intensive care unit acting as their own control to investigate the difference in PAT readings and readings from TAT in the core mode. Accuracy and precision were analyzed. There were 60 subjects, 41 males and 19 females, with mean age of 60.8 years, and 97% (n = 58) were post-cardiac surgery. There was a statistically significant difference between PAT and TAT (101.0°F [SD, 0.5°F] vs 100.5°F [SD, 0.8°F]; bias, -0.49°F; P < .001). Differences in temperature between the 2 methods were clinically significant (ie, >0.9°F different) in 15 of 60 cases (25%). No TAT measurements were 0.9 F greater than the corresponding PAT measurement (0%; 95% confidence interval, 0%-6%). These data demonstrate the accuracy of TAT when compared with PAT in those with temperatures of 100.4°F or greater. This study demonstrates that TAT set to core mode is accurate with a 0.5°F lower temperature than PAT. There was 25% in variability in precision of TAT.

Novel 4-Substituted-N,N-dimethyltetrahydronaphthalen-2-amines: Synthesis, Affinity, and In Silico Docking Studies at Serotonin 5-HT2-type and Histamine H1 G Protein-Coupled Receptors

PubMed Central

Sakhuja, Rajeev; Kondabolu, Krishnakanth; Córdova-Sintjago, Tania; Travers, Sean; Vincek, Adam S.; Kim, Myong Sang; Abboud, Khalil A.; Fang, Lijuan; Sun, Zhuming; Canal, Clinton E.; Booth, Raymond G.

2015-01-01

Syntheses were undertaken of derivatives of (2S, 4R)-(−)-trans-4-phenyl-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (4-phenyl-2-dimethylaminotetralin, PAT), a stereospecific agonist at the serotonin 5-HT2C G protein-coupled receptor (GPCR), with inverse agonist activity at 5-HT2A and 5-HT2B GPCRs. Molecular changes were made at the PAT C(4)-position, while preserving N, N-dimethyl substitution at the 2-position as well as trans-stereochemistry, structural features previously shown to be optimal for 5-HT2 binding. Affinities of analogs were determined at recombinant human 5-HT2 GPCRs in comparison to the phylogenetically closely-related histamine H1 GPCR, and in silico ligand docking studies were conducted at receptor molecular models to help interpret pharmacological results and guide future ligand design. In most cases, C(4)-substituted PAT analogs exhibited the same stereoselectivity ([−]-trans > [+]-trans) as the parent PAT across 5-HT2 and H1 GPCRs, albeit, with variable receptor selectivity. 4-(4′-substituted)-PAT analogs, however, demonstrated reversed stereoselectivity ([2S, 4R]-[+]-trans > [2S, 4R]-[−]-trans), with absolute configuration confirmed by single X-ray crystallographic data for the 4-(4′-Cl)-PAT analog. Pharmacological affinity results and computational results herein support further PAT drug development studies and provide a basis for predicting and interpreting translational results, including, for (+)-trans-4-(4′-Cl)-PAT and (−)-trans-4-(3′-Br)-PAT that were previously shown to be more potent and efficacious than their corresponding enantiomers in rodent models of psychoses, psychostimulant-induced behaviors, and compulsive feeding (‘binge-eating’). PMID:25703249

Role of mitogen activated protein kinases in skin tumorigenicity of Patulin

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

Saxena, Neha; Ansari, Kausar M.; Kumar, Rahul

2011-12-15

WHO has highlighted the need to evaluate dermal toxicity of mycotoxins including Patulin (PAT), detected in several fruits. In this study the skin carcinogenic potential of topically applied PAT was investigated. Single topical application of PAT (400 nmol) showed enhanced cell proliferation ({approx} 2 fold), along with increased generation of ROS and activation of ERK, p38 and JNK MAPKs, in mouse skin. PAT exposure also showed activation of downstream target proteins, c-fos, c-Jun and NF-{kappa}B transcription factors. Further, single topical application of PAT (400 nmol) followed by twice weekly application of TPA resulted in tumor formation after 14 weeks, indicatingmore » the tumor initiating activity of PAT. However no tumors were observed when PAT was used either as a complete carcinogen (80 nmol) or as a tumor promoter (20 nmol and 40 nmol) for 25 weeks. Histopathological findings of tumors found in PAT/TPA treated mice showed that these tumors were of squamous cell carcinoma type and similar to those found in the positive control group (DMBA/TPA) along with significant increase of lipid peroxidation and decrease in free sulfydryls, catalase, superoxide dismutase and glutathione reductase activities. The results suggest the possible role of free radicals in PAT mediated dermal tumorigenicity involving MAPKs. -- Highlights: Black-Right-Pointing-Pointer Single topical application of Patulin showed enhanced cell proliferation. Black-Right-Pointing-Pointer Patulin activate MAPKs, c-fos, c-Jun and NF-{kappa}B transcription factors. Black-Right-Pointing-Pointer Patulin showed skin tumor initiating potential. Black-Right-Pointing-Pointer We could not detect skin tumor promoting potential of Patulin at the tested dose. Black-Right-Pointing-Pointer However prolonged exposure of Patulin at a higher dose may promote tumor.« less

Effect of a Home-Based Lifestyle Intervention on Breastfeeding Initiation Among Socioeconomically Disadvantaged African American Women with Overweight or Obesity.

PubMed

Lewkowitz, Adam K; López, Julia D; Stein, Richard I; Rhoades, Janine S; Schulz, Rosa C; Woolfolk, Candice L; Macones, George A; Haire-Joshu, Debra; Cahill, Alison G

2018-06-18

Socioeconomically disadvantaged (SED) African American women with overweight or obesity are less likely to breastfeed. To test whether a home-based lifestyle intervention impacts breastfeeding initiation rates in SED African American women with overweight or obesity. This was a secondary analysis of a randomized controlled trial from October 2012 to March 2016 at a university-based hospital within the LIFE-Moms consortium. SED African American women with overweight or obesity and singleton gestations were randomized by 16 weeks to Parents as Teachers (PAT)-a home-based parenting support and child development educational intervention-or PAT+, PAT with additional content on breastfeeding. Participants completed a breastfeeding survey. Outcomes included breastfeeding initiation and reasons for not initiating or not continuing breastfeeding. One hundred eighteen women were included: 59 in PAT+; 59 in PAT. Breastfeeding initiation rates were similar in each group (78.00% in PAT+; 74.58% in PAT). On a one to four scale, with four denoting "very important," women in PAT+ and PAT were equally likely to rate their beliefs that formula was better than breast milk or breastfeeding would be too inconvenient as the most important reasons to not initiate breastfeeding. On the same scale, women similarly rated their difficulty latching or concern for low milk supply as the most important reasons for breastfeeding cessation. SED African American women with overweight or obesity who received a home-based educational intervention had higher breastfeeding rates than is reported nationally for black women (59%). However, the intervention with more breastfeeding content did not further increase breastfeeding rates or impact reasons for breastfeeding cessation. ClinicalTrials.gov : NCT01768793.

Inhibitory effects of processed Aconiti tuber on morphine-induced conditioned place preference in rats.

PubMed

Wu, Guiyun; Huang, Wenqi; Zhang, Hui; Li, Qiaobo; Zhou, Jun; Shu, Haihua

2011-06-14

Our previous studies indicated that processed Aconiti tuber (PAT), a traditional Chinese herbal medicine, had antinociceptive effects and inhibitory effects on morphine tolerance by activation of kappa-opioid receptor (KOR). Preclinical studies also demonstrated that KOR agonists functionally attenuate addictive behaviors of morphine, such as conditioned place preference (CPP). Therefore, we hypothesize that PAT may inhibit morphine-induced CPP in rats. (1) Five groups of rats (n=8 for each group) were alternately subcutaneous (s.c.) injected with morphine 10mg/kg (one group receive normal saline as a control) and normal saline for 8 days and oral co-administrated with distilled water or PAT 0.3, 1.0, or 3.0 g/kg daily on days 2-9 during CPP training, respectively. (2) Other four groups of rats were randomly s.c. injected with nor-binaltorphimine (nor-BNI; 5mg/kg) or normal saline (as a control) 120 min before alternately s.c. with morphine and normal saline and oral co-administrated with distilled water or PAT 3.0 g/kg daily. Each rat was acquired pre-conditioning and post-conditioning CPP data and assayed dynorphin concentrations by radioimmunoassay in rat's nucleus accumbens (NAc) after CPP training. (1) PAT 1.0 or 3.0 g/kg dose-dependently decreased the morphine-induced increase of CPP scores. (2) Nor-BNI completely antagonized the inhibition of PAT on morphine-induced CPP. (3) PAT dose-dependently increased dynorphin content in rats' NAc after CPP training. (1) PAT dose-dependently inhibited morphine-induced CPP. (2) The inhibition of PAT on morphine-induced CPP was probably due to activation of KOR by increasing dynorphin release in rats' NAc. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Will Progress in Science and Technology Avert or Accelerate Global Collapse? A Critical Analysis and Policy Recommendations

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

Huesemann, Michael H.; Huesemann, Joyce A.

Industrial society will move towards collapse if its total environmental impact (I), expressed either in terms of energy and materials use or in terms of pollution, increases with time, i.e., dI/dt > 0. The traditional interpretation of the I=PAT equation reflects the optimistic belief that technological innovation, particularly improvements in eco-efficiency, will significantly reduce the technology (T) factor, and thereby result in a corresponding decline in impact (I). Unfortunately, this interpretation of the I=PAT equation ignores the effects of technical change on the other two factors: population (P) and per capita affluence (A). A more heuristic formulation of this equationmore » is I=P(T)∙A(T)∙T in which the dependence of P and A on T is apparent. From historical evidence, it is clear that technological revolutions (tool-making, agricultural, and industrial) have been the primary driving forces behind successive population explosions, and that modern communication and transportation technologies have been employed to transform a large proportion of the world’s inhabitants into consumers of material- and energy-intensive products and services. In addition, factor analysis from neoclassical growth theory and the rebound effect provide evidence that science and technology have played a key role in contributing to rising living standards. While technological change has thus contributed to significant increases in both P and A, it has at the same time brought about considerable eco-efficiency improvements. Unfortunately, reductions in the T-factor have generally not been sufficiently rapid to compensate for the simultaneous increases in both P and A. As a result, total impact, in terms of energy production, mineral extraction, land-use and CO2 emissions, has in most cases increased with time, indicating that industrial society is nevertheless moving towards collapse. The belief that continued and even accelerated scientific research and technological innovation will automatically result in sustainability and avert collapse is at best mistaken. Innovations in science and technology will be necessary but alone will be insufficient for sustainability. Consequently, what is most needed are specific policies designed to decrease total impact, such as (a) halting population growth via effective population stabilization plans and better access to birth control methods, (b) reducing total matter-energy throughput and pollution by removing perverse subsidies, imposing regulations that limit waste discharges and the depletion of non-renewable resources, and implementing ecological tax reform, and (c) moving towards a steady-state economy in which per-capita affluence is stabilized at lower levels by replacing wasteful conspicuous material consumption with social alternatives known to enhance subjective well-being. While science and technology must play an important role in the implementation of these policies, none will be enacted without a fundamental change in society’s dominant values of growth and exploitation. Thus, value change is the most important prerequisite for avoiding global collapse.« less

Preparation, characterization, in vitro drug release, and cellular interactions of tailored paclitaxel releasing polyethylene oxide films for drug-coated balloons.

PubMed

Anderson, Jordan A; Lamichhane, Sujan; Remund, Tyler; Kelly, Patrick; Mani, Gopinath

2016-01-01

Drug-coated balloons (DCBs) are used to treat various cardiovascular diseases. Currently available DCBs carry drug on the balloon surface either solely or using different carriers. Several studies have shown that a significant amount of drug is lost in the blood stream during balloon tracking to deliver only a sub-therapeutic level of drug at the treatment site. This research is focused on developing paclitaxel (PAT) loaded polyethylene oxide (PEO) films (PAT-PEO) as a controlled drug delivery carrier for DCBs. An array of PAT-PEO films were developed in this study to provide tailored release of >90% of drug only at specific time intervals, which is the time frame required for carrying out balloon-based therapy. The characterizations of PAT-PEO films using SEM, FTIR, and DSC showed that the films developed were homogenous and the PAT was molecularly dispersed in the PEO matrix. Mechanical tests showed that most PAT-PEO films developed were flexible and ductile, with yield and tensile strengths not affected after PAT incorporation. The viability, proliferation, morphology, and phenotype of smooth muscle cells (SMCs) interacted with control-PEO and PAT-PEO films were investigated. All control-PEO and PAT-PEO films showed a significant inhibitory effect on the growth of SMCs, with the degree of inhibition strongly dependent on the w/v% of the polymer used. The PAT-PEO coating was produced on the balloons. The integrity of PAT-PEO coating was well maintained without any mechanical defects occurring during balloon inflation or deflation. The drug release studies showed that only 15% of the total PAT loaded was released from the balloons within the initial 1min (typical balloon tracking time), whereas 80% of the PAT was released between 1min and 4min (typical balloon treatment time). Thus, this study demonstrated the use of PEO as an alternate drug delivery system for the balloons. Atherosclerosis is primarily responsible for cardiovascular diseases (CVDs) in millions of patients every year. Drug-coated balloons (DCBs) are commonly used to treat various CVDs. However, in several currently used DCBs, a significant amount of drug is lost in the blood stream during balloon tracking to deliver only a sub-therapeutic level of drug at the treatment site. In this study, paclitaxel containing polyethylene oxide (PEO) films were developed to provide unique advantages including drug release profiles specifically tailored for balloon-based therapy, homogeneous films with molecularly dispersed drug, flexible and ductile films, and exhibits significant inhibitory effect on smooth muscle cell growth. Thus, this study demonstrated the use of PEO as an alternate drug delivery platform for DCBs to improve its efficacy. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Study of thermal resistance and in vitro bioaccessibility of patulin from artificially contaminated apple products.

PubMed

Raiola, Assunta; Meca, Giuseppe; García-Llatas, Guadalupe; Ritieni, Alberto

2012-09-01

Apple juices and purees represent categories widely consumed by whole population and above all children. Patulin (PAT) is a mycotoxin known for its acute and chronic effects in animals. Several studies indicate there is a risk associated to the PAT intake, through the consumption of purees and apple juices. In this study, apple juice and puree were prepared and artificially contaminated with PAT at 50 μg/kg and submitted to a thermal treatment simulating pasteurization to evaluate PAT's reduction. In a second phase of the work, apple products samples (n=7) included juices, nectars and purees belonging to different commercial brands were collected, artificially contaminated with PAT at 50 μg/L (limit established for PAT in juices) and 25 μg/kg (limit established for PAT in purees), digested with an in vitro gastrointestinal protocol and bioaccessibility values (%) were calculated. After thermal treatment, the PAT's loss evidenced in purees and juices was of 1.41 ± 0.52% and 62.62 ± 2.53% respectively. Related to the bioaccessibility data, two juices with pulp showed values of 70.89 ± 4.93 and 67.30 ± 10.76%; two purees showed levels of 58.15 ± 5.50 and 55.69 ± 4.73%, whereas nectar and two clarified juice showed percentages of 38.88 ± 2.42, 28.59 ± 0.46 and 25.28 ± 0.61%, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development and in-line validation of a Process Analytical Technology to facilitate the scale up of coating processes.

PubMed

Wirges, M; Funke, A; Serno, P; Knop, K; Kleinebudde, P

2013-05-05

Incorporation of an active pharmaceutical ingredient (API) into the coating layer of film-coated tablets is a method mainly used to formulate fixed-dose combinations. Uniform and precise spray-coating of an API represents a substantial challenge, which could be overcome by applying Raman spectroscopy as process analytical tool. In pharmaceutical industry, Raman spectroscopy is still mainly used as a bench top laboratory analytical method and usually not implemented in the production process. Concerning the application in the production process, a lot of scientific approaches stop at the level of feasibility studies and do not manage the step to production scale and process applications. The present work puts the scale up of an active coating process into focus, which is a step of highest importance during the pharmaceutical development. Active coating experiments were performed at lab and production scale. Using partial least squares (PLS), a multivariate model was constructed by correlating in-line measured Raman spectral data with the coated amount of API. By transferring this model, being implemented for a lab scale process, to a production scale process, the robustness of this analytical method and thus its applicability as a Process Analytical Technology (PAT) tool for the correct endpoint determination in pharmaceutical manufacturing could be shown. Finally, this method was validated according to the European Medicine Agency (EMA) guideline with respect to the special requirements of the applied in-line model development strategy. Copyright © 2013 Elsevier B.V. All rights reserved.

UV-Vis as quantification tool for solubilized lignin following a single-shot steam process.

PubMed

Lee, Roland A; Bédard, Charles; Berberi, Véronique; Beauchet, Romain; Lavoie, Jean-Michel

2013-09-01

In this short communication, UV/Vis was used as an analytical tool for the quantification of lignin concentrations in aqueous mediums. A significant correlation was determined between absorbance and concentration of lignin in solution. For this study, lignin was produced from different types of biomasses (willow, aspen, softwood, canary grass and hemp) using steam processes. Quantification was performed at 212, 225, 237, 270, 280 and 287 nm. UV-Vis quantification of lignin was found suitable for different types of biomass making this a timesaving analytical system that could lead to uses as Process Analytical Tool (PAT) in biorefineries utilizing steam processes or comparable approaches. Copyright © 2013 Elsevier Ltd. All rights reserved.

PAT: an intelligent authoring tool for facilitating clinical trial design.

PubMed

Tagaris, Anastasios; Andronikou, Vassiliki; Karanastasis, Efstathios; Chondrogiannis, Efthymios; Tsirmpas, Charalambos; Varvarigou, Theodora; Koutsouris, Dimitris

2014-01-01

Great investments are made by both private and public funds and a wealth of research findings is published, the research and development pipeline phases quite low productivity and tremendous delays. In this paper, we present a novel authoring tool which has been designed and developed for facilitating study design. Its underlying models are based on a thorough analysis of existing clinical trial protocols (CTPs) and eligibility criteria (EC) published in clinicaltrials.gov by domain experts. Moreover, its integration with intelligent decision support services and mechanisms linking the study design process with healthcare patient data as well as its direct access to literature designate it as a powerful tool offering great support to researchers during clinical trial design.

Hybrid modeling for quality by design and PAT-benefits and challenges of applications in biopharmaceutical industry.

PubMed

von Stosch, Moritz; Davy, Steven; Francois, Kjell; Galvanauskas, Vytautas; Hamelink, Jan-Martijn; Luebbert, Andreas; Mayer, Martin; Oliveira, Rui; O'Kennedy, Ronan; Rice, Paul; Glassey, Jarka

2014-06-01

This report highlights the drivers, challenges, and enablers of the hybrid modeling applications in biopharmaceutical industry. It is a summary of an expert panel discussion of European academics and industrialists with relevant scientific and engineering backgrounds. Hybrid modeling is viewed in its broader sense, namely as the integration of different knowledge sources in form of parametric and nonparametric models into a hybrid semi-parametric model, for instance the integration of fundamental and data-driven models. A brief description of the current state-of-the-art and industrial uptake of the methodology is provided. The report concludes with a number of recommendations to facilitate further developments and a wider industrial application of this modeling approach. These recommendations are limited to further exploiting the benefits of this methodology within process analytical technology (PAT) applications in biopharmaceutical industry. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using a Wrist-Worn Device Based on Peripheral Arterial Tonometry to Diagnose Obstructive Sleep Apnea: In-Laboratory and Ambulatory Validation

PubMed Central

Pittman, Stephen D.; Ayas, Najib T.; MacDonald, Mary M.; Malhotra, Atul; Fogel, Robert B.; White, David P.

2013-01-01

Study Objectives To assess the accuracy of a wrist-worn device (Watch_PAT 100) to diagnose obstructive sleep apnea in the home. Design Participants completed 2 overnight diagnostic studies with the test device: 1 night in the laboratory with concurrent polysomnography and 1 night in the home with only the Watch_PAT. The order of the laboratory and home study nights was random. The frequency of respiratory events on the PSG was quantified using indexes based on 2 definitions of hypopnea: the respiratory disturbance index (RDI) using American Academy of Sleep Medicine Task Force criteria for clinical research, also referred to as the Chicago criteria (RDI.C), and the Medicare guidelines (RDI.M). The Watch_PAT RDI (PAT RDI) and oxygen desaturation index (PAT ODI) were then evaluated against the polysomnography RDI.C and RDI.M, respectively, for both Watch_PAT diagnostic nights, yielding IN-LAB and HOME-LAB comparisons. Setting Sleep laboratory affiliated with a tertiary-care academic medical center. Patients 30 patients referred with suspected OSA. Interventions N/A. Measurements and Results The polysomnography and PAT measures were compared using the mean [2 SD] of the differences and the intra-class correlation coefficient (ICC). The receiver-operator characteristic curve was used to assess optimum sensitivity and specificity and calculate likelihood ratios. For the IN-LAB comparison, there was high concordance between RDI.C and PAT RDI (ICC = 0.88, mean difference 2.5 [18.9] events per hour); RDI.M and PAT ODI (ICC = 0.95, mean difference 1.4 [12.9] events per hour; and sleep time (ICC = 0.70, mean difference 7.0 [93.1] minutes) between the test device and PSG. For the HOME-LAB comparison, there was good concordance between RDI.C and PAT RDI (ICC = 0.72, mean difference 1.4 [30.1] events per hour) and RDI.M and PAT ODI (ICC = 0.80, mean difference 1.6 [26.4] events per hour) for the test device and PSG. Home studies were performed with no technical failures. Conclusions In a population of patients suspected of having obstructive sleep apnea, the Watch_PAT can quantify an ODI that compares very well with Medicare criteria for defining respiratory events and an RDI that compares favorably with Chicago criteria for defining respiratory events. The device can be used with a low failure rate for single use in the lab and home for self-administered testing. PMID:15453551

Ion Storage Tests with the High Performance Antimatter Trap (HiPAT)

NASA Technical Reports Server (NTRS)

Martin, James J.; Lewis, Raymond A.; Chakrabarti, Suman; Pearson, Boise; Schafer, Charles (Technical Monitor)

2002-01-01

The NASA/Marshall Space Flight Centers (NASA/MSFC) Propulsion Research Center (PRC) is evaluating an antiproton storage system, referred to as the High Performance Antiproton Trap (HiPAT). This interest stems from the sheer energy represented by matter/antimatter annihilation process with has an energy density approximately 10 order of magnitude above that of chemical propellants. In other terms, one gram of antiprotons contains the equivalent energy of approximately 23 space shuttle external tanks or ET's (each ET contains roughly 740,000 kgs of fuel and oxidizer). This incredible source of stored energy, if harnessed, would be an enabling technology for deep space mission where both spacecraft weight and propulsion performance are key to satisfying aggressive mission requirements. The HiPAT hardware consists of a 4 Tesla superconductor system, an ultra high vacuum test section (vacuum approaching 10(exp -12) torr), and a high voltage confinement electrode system (up to 20 kvolts operation). The current laboratory layout is illustrated. The HiPAT designed objectives included storage of up to 1 trillion antiprotons with corresponding lifetimes approaching 18 days. To date, testing has centered on the storage of positive hydrogen ions produced in situ by a stream of high-energy electrons that passes through the trapping region. However, due to space charge issues and electron beam compression as it passes through the HiPAT central field, current ion production is limited to less then 50,000 ions. Ion lifetime was determined by counting particle populations at the end of various storage time intervals. Particle detection was accomplished by destructively expelling the ions against a micro-channel plate located just outside the traps magnetic field. The effect of radio frequency (RF) stabilization on the lifetime of trapped particles was also examined. This technique, referred to as a rotating wall, made use of a segmented electrode located near the center of the trap on which various phases of a particular frequency were applied. Various experiments were performed illustrating the ability of an RF drive to both prolong and reduced the lifetimes of various ion species depending on the selected frequency. HiPAT is now being reconfigured for testing with an ion source that will provide both positive and negative hydrogen ions from an external source. This ion system shall provide higher fill capacity (order of million of ions per shot), stacking of multiple shots, and injection schemes typical of a realistic antiproton delivery system.

Overview of the High Performance Antiproton (HiPAT) Experiment

NASA Technical Reports Server (NTRS)

Martin, James J.; Sims, William H.; Chakrabarti, Suman; Pearson, Boise; Fant, Wallace E.; Lewis, Raymond A.; Rodgers, Stephen (Technical Monitor)

2002-01-01

The annihilation of matter with antimatter represents the highest energy density of any known reaction, producing 10(exp 8) MJ/g, approximately 10 orders of magnitude more energy per unit mass than chemical based combustion. To take the first step towards using this energy for propulsion applications the NASA MSFC Propulsion Research Center (PRC) has initiated a research activity examining the storage of low energy antiprotons. Storage was identified as a key enabling technology since it builds the experience base necessary to understand the handling of antiprotons for virtually all utilization and high-density storage concepts. To address this need, a device referred to as the High Performance Antiproton Trap (HiPAT) is under development at the NASA MSFC PRC. The HiPAT is an electromagnetic system (Penning-Malmberg design) consisting of a 4 Tesla superconductor, a high voltage confinement electrode system (operation up to 20 KV), and an ultra high vacuum test section (operating in the 10(exp -12) torr range). The system was designed to be portable with an ultimate goal of maintaining 10(exp 12) charged particles with a half-life of 18 days. Currently, this system is being experimentally evaluated using normal matter ions which are cheap to produce and relatively easy to handle. These normal ions provide a good indication of overall trap behavior, with the exception of assessing annihilation losses. The ions are produced external to HiPAT using two hydrogen ion sources, with adjustable beam energy and current. Ion are transported in a beam line and controlled through the use of electrostatic optics. These optics serve to both focus and gate the incoming ions, providing microsecond-timed pulses that are dynamically captured by cycling the HiPAT electric containment field like a 'trap door'. The layout of this system more closely simulates the operations expected at an actual antiproton production facility where 'packets' of antiprotons with pulse widths measured in 100's of nanoseconds could be provided. Initial dynamic capture experiments have been performed with both trap and ton source system functioning at approximately 10% of maximum levels, minimizing the potential for extraneous effects. Dynamic trapping techniques demonstrated the successful capture of millions of hydrogen ions with good agreement with the predicted loading based on the timing sequence, trap electric field, and ion beam current. These techniques will be expanded to examine multiple shot capture or 'stacking' to increase the total number of ions stored within HiPAT.

Multivariate analysis in the pharmaceutical industry: enabling process understanding and improvement in the PAT and QbD era.

PubMed

Ferreira, Ana P; Tobyn, Mike

2015-01-01

In the pharmaceutical industry, chemometrics is rapidly establishing itself as a tool that can be used at every step of product development and beyond: from early development to commercialization. This set of multivariate analysis methods allows the extraction of information contained in large, complex data sets thus contributing to increase product and process understanding which is at the core of the Food and Drug Administration's Process Analytical Tools (PAT) Guidance for Industry and the International Conference on Harmonisation's Pharmaceutical Development guideline (Q8). This review is aimed at providing pharmaceutical industry professionals an introduction to multivariate analysis and how it is being adopted and implemented by companies in the transition from "quality-by-testing" to "quality-by-design". It starts with an introduction to multivariate analysis and the two methods most commonly used: principal component analysis and partial least squares regression, their advantages, common pitfalls and requirements for their effective use. That is followed with an overview of the diverse areas of application of multivariate analysis in the pharmaceutical industry: from the development of real-time analytical methods to definition of the design space and control strategy, from formulation optimization during development to the application of quality-by-design principles to improve manufacture of existing commercial products.

Making a commitment to ethics in global health research partnerships: a practical tool to support ethical practice.

PubMed

Murphy, Jill; Hatfield, Jennifer; Afsana, Kaosar; Neufeld, Vic

2015-03-01

Global health research partnerships have many benefits, including the development of research capacity and improving the production and use of evidence to improve global health equity. These partnerships also include many challenges, with power and resource differences often leading to inequitable and unethical partnership dynamics. Responding to these challenges and to important gaps in partnership scholarship, the Canadian Coalition for Global Health Research (CCGHR) conducted a three-year, multi-regional consultation to capture the research partnership experiences of stakeholders in South Asia, Latin America, and sub-Saharan Africa. The consultation participants described persistent inequities in the conduct of global health research partnerships and called for a mechanism through which to improve accountability for ethical conduct within partnerships. They also called for a commitment by the global health research community to research partnership ethics. The Partnership Assessment Toolkit (PAT) is a practical tool that enables partners to openly discuss the ethics of their partnership and to put in place structures that create ethical accountability. Clear mechanisms such as the PAT are essential to guide ethical conduct to ensure that global health research partnerships are beneficial to all collaborators, that they reflect the values of the global health endeavor more broadly, and that they ultimately lead to improvements in health outcomes and health equity.

Expression of PAT and NPT II proteins during the developmental stages of a genetically modified pepper developed in Korea.

PubMed

Kim, Hyo Jin; Lee, Si Myung; Kim, Jae Kwang; Ryu, Tae Hun; Suh, Seok Cheol; Cho, Hyun Suk

2010-10-27

Estimation of the protein levels introduced in a biotechnology-derived product is conducted as part of an overall safety assessment. An enzyme-linked immunosorbent assay (ELISA) was used to analyze phosphinothricin acetyltransferase (PAT) and neomycin phosphotransferase II (NPT II) protein expression in a genetically modified (GM) pepper plant developed in Korea. PAT and NPT II expression levels, based on both dry weight and fresh weight, were variable among different plant generations and plant sections from isolated genetically modified organism (GMO) fields at four developmental stages. PAT expression was highest in leaves at anthesis (11.44 μg/gdw and 2.17 μg/gfw) and lowest in roots (0.12 μg/gdw and 0.01 μg/gfw). NPT II expression was also highest in leaves at anthesis (17.31 μg/gdw and 3.41 μg/gfw) and lowest in red pepper (0.65 μg/gdw and 0.12 μg/gfw). In pollen, PAT expression was 0.59-0.62 μg/gdw, while NPT II was not detected. Both PAT and NPT II showed a general pattern of decreased expression with progression of the growing season. As expected, PAT and NPT II protein expression was not detectable in control pepper plants.

Compact photoacoustic tomography system

NASA Astrophysics Data System (ADS)

Kalva, Sandeep Kumar; Pramanik, Manojit

2017-03-01

Photoacoustic tomography (PAT) is a non-ionizing biomedical imaging modality which finds applications in brain imaging, tumor angiogenesis, monitoring of vascularization, breast cancer imaging, monitoring of oxygen saturation levels etc. Typical PAT systems uses Q-switched Nd:YAG laser light illumination, single element large ultrasound transducer (UST) as detector. By holding the UST in horizontal plane and moving it in a circular motion around the sample in full 2π radians photoacoustic data is collected and images are reconstructed. The horizontal positioning of the UST make the scanning radius large, leading to larger water tank and also increases the load on the motor that rotates the UST. To overcome this limitation, we present a compact photoacoustic tomographic (ComPAT) system. In this ComPAT system, instead of holding the UST in horizontal plane, it is held in vertical plane and the photoacoustic waves generated at the sample are detected by the UST after it is reflected at 45° by an acoustic reflector attached to the transducer body. With this we can reduce the water tank size and load on the motor, thus overall PAT system size can be reduced. Here we show that with the ComPAT system nearly similar PA images (phantom and in vivo data) can be obtained as that of the existing PAT systems using both flat and cylindrically focused transducers.

Characterization of human palmitoyl-acyl transferase activity using peptides that mimic distinct palmitoylation motifs.

PubMed Central

Varner, Amanda S; Ducker, Charles E; Xia, Zuping; Zhuang, Yan; De Vos, Mackenzie L; Smith, Charles D

2003-01-01

The covalent attachment of palmitate to proteins commonly occurs on cysteine residues near either N-myristoylated glycine residues or C-terminal farnesylated cysteine residues. It therefore seems likely that multiple palmitoyl-acyl transferase (PAT) activities exist to recognize and modify these distinct palmitoylation motifs. To evaluate this possibility, two synthetic peptides representing these palmitoylation motifs, termed MyrGCK(NBD) and FarnCNRas(NBD), were used to characterize PAT activity under a variety of conditions. The human tumour cell lines MCF-7 and Hep-G2 each demonstrated high levels of PAT activity towards both peptides. In contrast, normal mouse fibroblasts (NIH/3T3 cells) demonstrated PAT activity towards the myristoylated substrate peptide but not the farnesylated peptide, while ras -transformed NIH/3T3 cells were able to palmitoylate the FarnCNRas(NBD) peptide. The kinetic parameters for PAT activity were determined using membranes from MCF-7 cells, and indicated that the K (m) values for palmitoyl-CoA were identical for PAT activity towards the two substrate peptides; however, the K (m) for MyrGCK(NBD) was 5-fold lower than the K (m) for FarnCNRas(NBD). PAT activity towards the two substrate peptides was dose-dependently inhibited by 2-bromopalmitate and 3-(1-oxo-hexadecyl)oxiranecarboxamide (16C; IC(50) values of approx. 4 and 1.3 microM, respectively); however, 2-bromopalmitate was found to be uncompetitive with respect to palmitoyl-CoA, whereas 16C was competitive. To seek additional evidence for multiple PATs, the effects of altering the assay conditions on the palmitoylation of MyrGCK(NBD) and FarnCNRas(NBD) were compared. PAT activity towards the two peptide substrates was modulated similarly by changing the ionic strength or incubation temperature, or by the addition of dithiothreitol. In contrast, the enzymic palmitoylation of the two peptides was differentially affected by N -ethylmaleimide and thermal denaturation. Overall, these data demonstrate that the enzymic palmitoylation of farnesyl- and myristoyl-containing peptide substrates can be differentiated, suggesting that multiple motif-specific PATs exist. PMID:12670300

Flow-mediated dilation and peripheral arterial tonometry are disturbed in preeclampsia and reflect different aspects of endothelial function.

PubMed

Mannaerts, Dominique; Faes, Ellen; Goovaerts, Inge; Stoop, Tibor; Cornette, Jerome; Gyselaers, Wilfried; Spaanderman, Marc; Van Craenenbroeck, Emeline M; Jacquemyn, Yves

2017-11-01

Endothelial function and arterial stiffness are known to be altered in preeclamptic pregnancies. Previous studies have shown conflicting results regarding the best technique for assessing vascular function in pregnancy. In this study, we made a comprehensive evaluation of in vivo vascular function [including flow-mediated dilatation (FMD), peripheral arterial tonometry (PAT), and arterial stiffness] in preeclamptic patients and compared them with normal pregnancies. In addition, we assessed the relation between vascular function and systemic inflammation. Fourteen patients with preeclampsia (PE) and 14 healthy pregnant controls were included. Endothelial function was determined by FMD and PAT and arterial stiffness by carotid-femoral pulse-wave velocity and augmentation index. Systemic inflammation was assessed using mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR). The reactive hyperemia index, assessed using PAT, is decreased at the third trimester compared with the first trimester in a normal, uncomplicated pregnancy ( P = 0.001). Arterial stiffness is significantly higher in PE versus normal pregnancy ( P < 0.001). Endothelial function, obtained by FMD, is deteriorated in PE versus normal pregnancy ( P = 0.015), whereas endothelial function assessment by PAT is improved in PE versus normal pregnancy ( P = 0.001). Systemic inflammation (MPV and NLR) increases during normal pregnancy. FMD and PAT are disturbed in PE. Endothelial function, assessed by FMD and PAT, shows distinct results. This may indicate that measurements with FMD and PAT reflect different aspects of endothelial function and that PAT should not be used as a substitute for FMD as a measure of endothelial function in pregnancy. Copyright © 2017 the American Physiological Society.

The Gene pat-2, Which Induces Natural Parthenocarpy, Alters the Gibberellin Content in Unpollinated Tomato Ovaries1

PubMed Central

Fos, Mariano; Nuez, Fernando; García-Martínez, José L.

2000-01-01

We investigated the role of gibberellins (GAs) in the effect of pat-2, a recessive mutation that induces facultative parthenocarpic fruit development in tomato (Lycopersicon esculentum Mill.) using near-isogenic lines with two different genetic backgrounds. Unpollinated wild-type Madrigal (MA/wt) and Cuarenteno (CU/wt) ovaries degenerated, but GA3 application induced parthenocarpic fruit growth. On the contrary, parthenocarpic growth of MA/pat-2 and CU/pat-2 fruits, which occurs in the absence of pollination and hormone application, was not affected by GA3. Pollinated MA/wt and parthenocarpic MA/pat-2 ovary development was negated by paclobutrazol, and this inhibitory effect was counteracted by GA3. The main GAs of the early-13-hydroxylation pathway (GA1, GA3, GA8, GA19, GA20, GA29, GA44, GA53, and, tentatively, GA81) and two GAs of the non-13-hydroxylation pathway (GA9 and GA34) were identified in MA/wt ovaries by gas chromatography-selected ion monitoring. GAs were quantified in unpollinated ovaries at flower bud, pre-anthesis, and anthesis. In unpollinated MA/pat-2 and CU/pat-2 ovaries, the GA20 content was much higher (up to 160 times higher) and the GA19 content was lower than in the corresponding non-parthenocarpic ovaries. The application of an inhibitor of 2-oxoglutarate-dependent dioxygenases suggested that GA20 is not active per se. The pat-2 mutation may increase GA 20-oxidase activity in unpollinated ovaries, leading to a higher synthesis of GA20, the precursor of an active GA. PMID:10677440

Electrochemical determination of dopamine and ascorbic acid at a novel gold nanoparticles distributed poly(4-aminothiophenol) modified electrode.

PubMed

Gopalan, Anantha Iyengar; Lee, Kwang-Pill; Manesh, Kalayil Manian; Santhosh, Padmanabhan; Kim, Jun Heon; Kang, Jae Soo

2007-03-15

A modified electrode is fabricated by embedding gold nanoparticles into a layer of electroactive polymer, poly(4-aminothiophenol) (PAT) on the surface of glassy carbon (GC) electrode. Cyclic voltammetry (CV) is performed to deposit PAT and concomitantly deposit Au nanoparticles. Field emission transmission electron microscopic image of the modified electrode, PAT-Au(nano)-ME, indicates the presence of uniformly distributed Au nanoparticles having the sizes of 8-10nm. Electrochemical behavior of the PAT-Au(nano)-ME towards detection of ascorbic acid (AA) and dopamine (DA) is studied using CV. Electrocatalytic determination of DA in the presence of fixed concentration of AA and vice versa, are studied using differential pulse voltammetry (DPV). PAT-Au(nano)-ME exhibits two well defined anodic peaks at the potential of 75 and 400mV for the oxidation of AA and DA, respectively with a potential difference of 325mV. Further, the simultaneous determination of AA and DA is studied by varying the concentration of AA and DA. PAT-Au(nano)-ME exhibits selectivity and sensitivity for the simultaneous determination of AA and DA without fouling by the oxidation products of AA or DA. PAT and Au nanoparticles provide synergic influence on the accurate electrochemical determination of AA or DA from a mixture having any one of the component (AA or DA) in excess. The practical analytical utilities of the PAT-Au(nano)-ME are demonstrated by the determination of DA and AA in dopamine hydrochloride injection and human blood serum samples.

Motorized photoacoustic tomography probe for label-free improvement in image quality

NASA Astrophysics Data System (ADS)

Sangha, Gurneet S.; Hale, Nick H.; Goergen, Craig J.

2018-02-01

One of the challenges in high-resolution in vivo lipid-based photoacoustic tomography (PAT) is improving penetration depth and signal-to-noise ratio (SNR) past subcutaneous fat absorbers. A potential solution is to create optical manipulation techniques to maximize the photon density within a region of interest. Here, we present a motorized PAT probe that is capable of tuning the depth in which light is focused, as well as substantially reducing probe-skin artifacts that can obscure image interpretation. Our PAT system consists of a Nd:YAG laser (Surelite EX, Continuum) coupled with a 40 MHz central frequency ultrasound transducer (Vevo2100, FUJIFILM Visual Sonics). This system allows us to deliver 10 Hz, 5 ns light pulses with fluence of 40 mJ/cm2 to the tissue interest and reconstruct PAT and ultrasound images with axial resolutions of 125 µm and 40 µm, respectively. The motorized PAT holder was validated by imaging a polyethylene-50 tubing embedded polyvinyl alcohol phantom and periaortic fat on apolipoprotein-E deficient mice. We used 1210 nm light for this study, as this wavelength generates PAT signal for both lipids and polyethylene-50 tubes. Ex vivo results showed a 2 mm improvement in penetration depth and in vivo experiments showed an increase in lipid SNR of at least 62%. Our PAT probe also utilizes a 7 μm aluminum filter to prevent in vivo probe-skin reflection artifacts that have been previously resolved using image post-processing techniques. Using this optimized PAT probe, we can direct light to various depths within tissue to improve image quality and prevent reflection artifacts.

Flexible continuous manufacturing platforms for solid dispersion formulations

NASA Astrophysics Data System (ADS)

Karry-Rivera, Krizia Marie

In 2013 16,000 people died in the US due to overdose from prescription drugs and synthetic narcotics. As of that same year, 90% of new molecular entities in the pharmaceutical drug pipeline are classified as poor water-soluble. The work in this dissertation aims to design, develop and validate platforms that solubilize weak acids and can potentially deter drug abuse. These platforms are based on processing solid dispersions via solvent-casting and hot-melt extrusion methods to produce oral transmucosal films and melt tablets. To develop these platforms, nanocrystalline suspensions and glassy solutions were solvent-casted in the form of films after physicochemical characterizations of drug-excipient interactions and design of experiment approaches. A second order model was fitted to the emulsion diffusion process to predict average nanoparticle size and for process optimization. To further validate the manufacturing flexibility of the formulations, glassy solutions were also extruded and molded into tablets. This process included a systematic quality-by-design (QbD) approach that served to identify the factors affecting the critical quality attributes (CQAs) of the melt tablets. These products, due to their novelty, lack discriminatory performance tests that serve as predictors to their compliance and stability. Consequently, Process Analytical Technology (PAT) tools were integrated into the continuous manufacturing platform for films. Near-infrared (NIR) spectroscopy, including chemical imaging, combined with deconvolution algorithms were utilized for a holistic assessment of the effect of formulation and process variables on the product's CQAs. Biorelevant dissolution protocols were then established to improve the in-vivo in-vitro correlation of the oral transmucosal films. In conclusion, the work in this dissertation supports the delivery of poor-water soluble drugs in products that may deter abuse. Drug nanocrystals ensured high bioavailability, while glassy solutions enabled drug solubilization in polymer matrices. PAT tools helped in characterizing the micro and macro structure of the product while also used as a control strategy for manufacturing. The systematic QbD assessment enabled identification of the variables that significantly affected melt tablet performance and their potential as an abuse deterrent product. Being that these glassy products are novel systems, biorelevant protocols for testing dissolution performance of films were also developed.

On-line near infrared spectroscopy as a Process Analytical Technology (PAT) tool to control an industrial seeded API crystallization.

PubMed

Schaefer, C; Lecomte, C; Clicq, D; Merschaert, A; Norrant, E; Fotiadu, F

2013-09-01

The final step of an active pharmaceutical ingredient (API) manufacturing synthesis process consists of a crystallization during which the API and residual solvent contents have to be quantified precisely in order to reach a predefined seeding point. A feasibility study was conducted to demonstrate the suitability of on-line NIR spectroscopy to control this step in line with new version of the European Medicines Agency (EMA) guideline [1]. A quantitative method was developed at laboratory scale using statistical design of experiments (DOE) and multivariate data analysis such as principal component analysis (PCA) and partial least squares (PLS) regression. NIR models were built to quantify the API in the range of 9-12% (w/w) and to quantify the residual methanol in the range of 0-3% (w/w). To improve the predictive ability of the models, the development procedure encompassed: outliers elimination, optimum model rank definition, spectral range and spectral pre-treatment selection. Conventional criteria such as, number of PLS factors, R(2), root mean square errors of calibration, cross-validation and prediction (RMSEC, RMSECV, RMSEP) enabled the selection of three model candidates. These models were tested in the industrial pilot plant during three technical campaigns. Results of the most suitable models were evaluated against to the chromatographic reference methods. Maximum relative bias of 2.88% was obtained about API target content. Absolute bias of 0.01 and 0.02% (w/w) respectively were achieved at methanol content levels of 0.10 and 0.13% (w/w). The repeatability was assessed as sufficient for the on-line monitoring of the 2 analytes. The present feasibility study confirmed the possibility to use on-line NIR spectroscopy as a PAT tool to monitor in real-time both the API and the residual methanol contents, in order to control the seeding of an API crystallization at industrial scale. Furthermore, the successful scale-up of the method proved its capability to be implemented in the manufacturing plant with the launch of the new API process. Copyright © 2013 Elsevier B.V. All rights reserved.

Rationale, Design, and Methods of the Preschool ADHD Treatment Study (PATS)

ERIC Educational Resources Information Center

Kollins, Scott; Greenhill, Laurence; Swanson, James; Wigal, Sharon; Abikoff, Howard; McCracken, James; Riddle, Mark; McGough, James; Vitiello, Benedetto; Wigal, Tim; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Davies, Mark; Cunningham, Charles; Bauzo, Audrey

2006-01-01

Objective: To describe the rationale and design of the Preschool ADHD Treatment Study (PATS). Method: PATS was a National Institutes of Mental Health-funded, multicenter, randomized, efficacy trial designed to evaluate the short-term (5 weeks) efficacy and long-term (40 weeks) safety of methylphenidate (MPH) in preschoolers with…

Decapping activators in Saccharomyces cerevisiae act by multiple mechanisms.

PubMed

Nissan, Tracy; Rajyaguru, Purusharth; She, Meipei; Song, Haiwei; Parker, Roy

2010-09-10

Eukaryotic mRNA degradation often occurs in a process whereby translation initiation is inhibited and the mRNA is targeted for decapping. In yeast cells, Pat1, Scd6, Edc3, and Dhh1 all function to promote decapping by an unknown mechanism(s). We demonstrate that purified Scd6 and a region of Pat1 directly repress translation in vitro by limiting the formation of a stable 48S preinitiation complex. Moreover, while Pat1, Edc3, Dhh1, and Scd6 all bind the decapping enzyme, only Pat1 and Edc3 enhance its activity. We also identify numerous direct interactions between Pat1, Dcp1, Dcp2, Dhh1, Scd6, Edc3, Xrn1, and the Lsm1-7 complex. These observations identify three classes of decapping activators that function to directly repress translation initiation and/or stimulate Dcp1/2. Moreover, Pat1 is identified as critical in mRNA decay by first inhibiting translation initiation, then serving as a scaffold to recruit components of the decapping complex, and finally activating Dcp2. Copyright © 2010 Elsevier Inc. All rights reserved.

An investigation of multitasking information behavior and the influence of working memory and flow

NASA Astrophysics Data System (ADS)

Alexopoulou, Peggy; Hepworth, Mark; Morris, Anne

2015-02-01

This study explored the multitasking information behaviour of Web users and how this is influenced by working memory, flow and Personal, Artefact and Task characteristics, as described in the PAT model. The research was exploratory using a pragmatic, mixed method approach. Thirty University students participated; 10 psychologists, 10 accountants and 10 mechanical engineers. The data collection tools used were: pre and post questionnaires, a working memory test, a flow state scale test, audio-visual data, web search logs, think aloud data, observation, and the critical decision method. All participants searched information on the Web for four topics: two for which they had prior knowledge and two more without prior knowledge. Perception of task complexity was found to be related to working memory. People with low working memory reported a significant increase in task complexity after they had completed information searching tasks for which they had no prior knowledge, this was not the case for tasks with prior knowledge. Regarding flow and task complexity, the results confirmed the suggestion of the PAT model (Finneran and Zhang, 2003), which proposed that a complex task can lead to anxiety and low flow levels as well as to perceived challenge and high flow levels. However, the results did not confirm the suggestion of the PAT model regarding the characteristics of web search systems and especially perceived vividness. All participants experienced high vividness. According to the PAT model, however, only people with high flow should experience high levels of vividness. Flow affected the degree of change of knowledge of the participants. People with high flow gained more knowledge for tasks without prior knowledge rather than people with low flow. Furthermore, accountants felt that tasks without prior knowledge were less complex at the end of the web seeking procedure than psychologists and mechanical engineers. Finally, the three disciplines appeared to differ regarding the multitasking information behaviour characteristics such as queries, web search sessions and opened tabs/windows.

Impaired vasoreactivity in mildly disabled CADASIL patients.

PubMed

Campolo, Jonica; De Maria, Renata; Frontali, Marina; Taroni, Franco; Inzitari, Domenico; Federico, Antonio; Romano, Silvia; Puca, Emanuele; Mariotti, Caterina; Tomasello, Chiara; Pantoni, Leonardo; Pescini, Francesca; Dotti, Maria Teresa; Stromillo, Maria Laura; De Stefano, Nicola; Tavani, Alessandra; Parodi, Oberdan

2012-03-01

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a rare genetic disease caused by NOTCH3 gene mutations. A dysfunction in vasoreactivity has been proposed as an early event in the pathogenesis of the disease. The aim of this study was to verify whether endothelium dependent and/or independent function is altered in CADASIL patients with respect to controls. Vasoreactivity was studied by a non-invasive pletismographic method in 49 mildly disabled CADASIL patients (30-65 years, 58% male, Rankin scale ≤2) and 25 controls. Endothelium dependent vasodilatation was assessed by reactive hyperaemia (flow mediated dilation-peripheral arterial tone (FMD-PAT)) and endothelium independent vasoreactivity by glyceryl trinitrate (GTN) administration (GTN-PAT). Patients and controls showed comparable age, gender and cardiovascular risk factor distribution. GTN-PAT values were significantly lower in CADASIL patients (1.54 (1.01 to 2.25)) than in controls (1.89 (1.61 to 2.59); p=0.041). FMD-PAT scores did not differ between patients and controls (1.88 (1.57 to 2.43) vs 2.08 (1.81 to 2.58); p=0.126) but 17 CADASIL patients (35%) had FMD-PAT scores below the fifth percentile of controls. FMD-PAT and GTN-PAT values correlated both in controls (ρ=0.648, p<0.001) and CADASIL patients (ρ=0.563, p<0.001). By multivariable logistic regression for clinical and laboratory variables, only GTN-PAT (OR 0.39, 95% CI 0.15 to 0.97; p=0.044) was independently associated with FMD-PAT below the fifth percentile in CADASIL patients. The impaired vasoreactivity observed in CADASIL patients highlights the fact that both endothelial and smooth muscle functional alterations may already be present in mildly disabled subjects. The improvement in vascular function could be a new target for pharmacological trials in CADASIL patients.

RF Manipulation and Detection of Protons in the High Performance Antiproton Trap (HiPAT)

NASA Technical Reports Server (NTRS)

Martin, James J.; Lewis, Raymond A.; Pearson, J. Boise; Sims, W. Herb; Chakrabarti, Suman; Fant, Wallace E.; McDonald, Stan

2003-01-01

The significant energy density of matter-antimatter annihilation is attractive to the designers of future space propulsion systems, with the potential to offer a highly compact source of power. Many propulsion concepts exist that could take advantage of matter-antimatter reactions, and current antiproton production rates are sufficient to support basic proof-of-principle evaluation of technology associated with antimatter-derived propulsion. One enabling technology for such experiments is portable storage of low energy antiprotons, allowing antiprotons to be trapped, stored, and transported for use at an experimental facility.

Diauxic shift-dependent relocalization of decapping activators Dhh1 and Pat1 to polysomal complexes

PubMed Central

Drummond, Sheona P.; Hildyard, John; Firczuk, Helena; Reamtong, Onrapak; Li, Ning; Kannambath, Shichina; Claydon, Amy J.; Beynon, Robert J.; Eyers, Claire E.; McCarthy, John E. G.

2011-01-01

Dhh1 and Pat1 in yeast are mRNA decapping activators/translational repressors thought to play key roles in the transition of mRNAs from translation to degradation. However, little is known about the physical and functional relationships between these proteins and the translation machinery. We describe a previously unknown type of diauxic shift-dependent modulation of the intracellular locations of Dhh1 and Pat1. Like the formation of P bodies, this phenomenon changes the spatial relationship between components involved in translation and mRNA degradation. We report significant spatial separation of Dhh1 and Pat1 from ribosomes in exponentially growing cells. Moreover, biochemical analyses reveal that these proteins are excluded from polysomal complexes in exponentially growing cells, indicating that they may not be associated with active states of the translation machinery. In contrast, under diauxic growth shift conditions, Dhh1 and Pat1 are found to co-localize with polysomal complexes. This work suggests that Dhh1 and Pat1 functions are modulated by a re-localization mechanism that involves eIF4A. Pull-down experiments reveal that the intracellular binding partners of Dhh1 and Pat1 change as cells undergo the diauxic growth shift. This reveals a new dimension to the relationship between translation activity and interactions between mRNA, the translation machinery and decapping activator proteins. PMID:21712243

Implication of an Aldehyde Dehydrogenase Gene and a Phosphinothricin N-Acetyltransferase Gene in the Diversity of Pseudomonas cichorii Virulence

PubMed Central

Tanaka, Masayuki; Wali, Ullah Md; Nakayashiki, Hitoshi; Fukuda, Tatsuya; Mizumoto, Hiroyuki; Ohnishi, Kouhei; Kiba, Akinori; Hikichi, Yasufumi

2011-01-01

Pseudomonas cichorii harbors the hrp genes. hrp-mutants lose their virulence on eggplant but not on lettuce. A phosphinothricin N-acetyltransferase gene (pat) is located between hrpL and an aldehyde dehydrogenase gene (aldH) in the genome of P. cichorii. Comparison of nucleotide sequences and composition of the genes among pseudomonads suggests a common ancestor of hrp and pat between P. cichorii strains and P. viridiflava strains harboring the single hrp pathogenicity island. In contrast, phylogenetic diversification of aldH corresponded to species diversification amongst pseudomonads. In this study, the involvement of aldH and pat in P. cichorii virulence was analyzed. An aldH-deleted mutant (ΔaldH) and a pat-deleted mutant (Δpat) lost their virulence on eggplant but not on lettuce. P. cichorii expressed both genes in eggplant leaves, independent of HrpL, the transcriptional activator for the hrp. Inoculation into Asteraceae species susceptible to P. cichorii showed that the involvement of hrp, pat and aldH in P. cichorii virulence is independent of each other and has no relationship with the phylogeny of Asteraceae species based on the nucleotide sequences of ndhF and rbcL. It is thus thought that not only the hrp genes but also pat and aldH are implicated in the diversity of P. cichorii virulence on susceptible host plant species. PMID:24704843

CrossTalk. The Journal of Defense Software Engineering. Volume 13, Number 6, June 2000

DTIC Science & Technology

2000-06-01

Techniques for Efficiently Generating and Testing Software This paper presents a proven process that uses advanced tools to design, develop and test... optimal software. by Keith R. Wegner Large Software Systems—Back to Basics Development methods that work on small problems seem to not scale well to...Ability Requirements for Teamwork: Implications for Human Resource Management, Journal of Management, Vol. 20, No. 2, 1994. 11. Ferguson, Pat, Watts S

Development and validation of a biologically realistic tissue-mimicking material for photoacoustics and other bimodal optical-acoustic modalities

NASA Astrophysics Data System (ADS)

Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Pfefer, T. Joshua

2017-03-01

Recent years have seen rapid development of hybrid optical-acoustic imaging modalities with broad applications in research and clinical imaging, including photoacoustic tomography (PAT), photoacoustic microscopy, and ultrasound-modulated optical tomography. Tissue-mimicking phantoms are an important tool for objectively and quantitatively simulating in vivo imaging system performance. However, no standard tissue phantoms exist for such systems. One major challenge is the development of tissue-mimicking materials (TMMs) that are both highly stable and possess biologically realistic properties. To address this need, we have explored the use of various formulations of PVC plastisol (PVCP) based on varying mixtures of several liquid plasticizers. We developed a custom PVCP formulation with optical absorption and scattering coefficients, speed of sound, and acoustic attenuation that are tunable and tissue-relevant. This TMM can simulate different tissue compositions and offers greater mechanical strength than hydrogels. Optical properties of PVCP samples with varying composition were characterized using integrating sphere spectrophotometry and the inverse adding-doubling method. Acoustic properties were determined using a broadband pulse-transmission technique. To demonstrate the utility of this bimodal TMM, we constructed an image quality phantom designed to enable quantitative evaluation of PAT spatial resolution. The phantom was imaged using a custom combined PAT-ultrasound imaging system. Results indicated that this more biologically realistic TMM produced performance trends not captured in simpler liquid phantoms. In the future, this TMM may be broadly utilized for performance evaluation of optical, acoustic, and hybrid optical-acoustic imaging systems.

Developing an Adaptability Training Strategy and Policy for the DoD

DTIC Science & Technology

2008-10-01

might include monitoring of trainees using electroencephalogram ( EEG ) technology to gain neurofeedback during scenario performance. In order to...group & adequate sample; pre and post iii. Possibly including EEG monitoring (and even neurofeedback ) 4. Should seek to determine general...Dr. John Cowan has developed a system called the Peak Achievement Trainer (PAT) EEG , which traces electrical activity in the brain and provides

Vigabatrin transport across the human intestinal epithelial (Caco-2) brush-border membrane is via the H+-coupled amino-acid transporter hPAT1

PubMed Central

Abbot, Emily L; Grenade, Danielle S; Kennedy, David J; Gatfield, Kelly M; Thwaites, David T

2005-01-01

The aim of this investigation was to determine if the human proton-coupled amino-acid transporter 1 (hPAT1 or SLC36A1) is responsible for the intestinal uptake of the orally-administered antiepileptic agent 4-amino-5-hexanoic acid (vigabatrin). The Caco-2 cell line was used as a model of the human small intestinal epithelium. Competition experiments demonstrate that [3H]GABA uptake across the apical membrane was inhibited by vigabatrin and the GABA analogues trans-4-aminocrotonic acid (TACA) and guvacine, whereas 1-(aminomethyl)cyclohexaneacetic acid (gabapentin) had no affect. Experiments with 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-loaded Caco-2 cells demonstrate that apical exposure to vigabatrin and TACA induce comparable levels of intracellular acidification (due to H+/amino-acid symport) to that generated by GABA, suggesting that they are substrates for a H+-coupled absorptive transporter such as hPAT1. In hPAT1 and mPAT1-expressing Xenopus laevis oocytes [3H]GABA uptake was inhibited by vigabatrin, TACA and guvacine, whereas gabapentin failed to inhibit [3H]GABA uptake. In Na+-free conditions, vigabatrin and TACA evoked similar current responses (due to H+/amino-acid symport) in hPAT1-expressing oocytes under voltage-clamp conditions to that induced by GABA (whereas no current was observed in water-injected oocytes) consistent with the ability of these GABA analogues to inhibit [3H]GABA uptake. This study demonstrates that hPAT1 is the carrier responsible for the uptake of vigabatrin across the brush-border membrane of the small intestine and emphasises the therapeutic potential of hPAT1 as a delivery route for orally administered, clinically significant GABA-related compounds. PMID:16331283

Relations of Digital Vascular Function, Cardiovascular Risk Factors, and Arterial Stiffness: The Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil) Cohort Study

PubMed Central

Brant, Luisa C. C.; Hamburg, Naomi M.; Barreto, Sandhi M.; Benjamin, Emelia J.; Ribeiro, Antonio L. P.

2014-01-01

Background Vascular dysfunction is an early expression of atherosclerosis and predicts cardiovascular (CV) events. Peripheral arterial tonometry (PAT) evaluates basal pulse amplitude (BPA), endothelial function (PAT ratio), and wave reflection (PAT‐AIx) in the digital microvessels. In Brazilian adults, we investigated the correlations of PAT responses to CV risk factors and to carotid‐femoral pulse wave velocity (PWV), a measure of arterial stiffness. Methods and Results In a cross‐sectional study, 1535 participants of the ELSA‐Brasil cohort underwent PAT testing (52±9 years; 44% women). In multivariable analyses, more‐impaired BPA and PAT ratios were associated with male sex, higher body mass index (BMI), and total cholesterol/high‐density lipoprotein. Higher age and triglycerides were related to higher BPA, whereas lower systolic blood pressure, hypertension (HTN) treatment, and prevalent CV disease (CVD) were associated with lower PAT ratio. PAT‐AIx correlated positively with female sex, advancing age, systolic and diastolic blood pressures, and smoking and inversely to heart rate, height, BMI, and prevalent CVD. Black race was associated with lower BPA, higher PAT ratio, and PAT‐AIx. Microvessel vasodilator function was not associated with PWV. Higher PAT‐AIx was modestly correlated to higher PWV and PAT ratio and inversely correlated to BPA. Conclusion Metabolic risk factors are related to impaired microvessel vasodilator function in Brazil. However, in contrast to studies from the United States, black race was not associated with an impaired microvessel vasodilator response, implying that vascular function may vary by race across populations. PAT‐AIx relates to HTN, may be a valid measure of wave reflection, and provides distinct information from arterial stiffness. PMID:25510401

A GRP78-Directed Monoclonal Antibody Recaptures Response in Refractory Multiple Myeloma with Extramedullary Involvement.

PubMed

Rasche, Leo; Menoret, Emmanuelle; Dubljevic, Valentina; Menu, Eline; Vanderkerken, Karin; Lapa, Constantin; Steinbrunn, Torsten; Chatterjee, Manik; Knop, Stefan; Düll, Johannes; Greenwood, Deanne L; Hensel, Frank; Rosenwald, Andreas; Einsele, Hermann; Brändlein, Stephanie

2016-09-01

Glucose-regulated protein (GRP) 78 is overexpressed in multiple myeloma, and both its surface expression and its biologic significance as key sensor of the unfolded protein response make GRP78 an ideal candidate for immunotherapeutic intervention. The monoclonal antibody PAT-SM6 targets surface GRP78 and leads to disease stabilization when used as single agent in a clinical trial. In this article, we evaluated expression of GRP78 in relapsed-refractory disease and explored PAT-SM6 therapy in combination regimens. GRP78 expression was immunohistochemically analyzed during disease progression and development of drug resistance throughout different stages of multiple myeloma. Activity of PAT-SM6 was evaluated in combination with anti-multiple myeloma agents lenalidomide, bortezomib, and dexamethasone in vitro Finally, we report on a multiple myeloma patient with relapsed-refractory disease treated with PAT-SM6 in combination with bortezomib and lenalidomide. Although sGRP78 expression was present at all stages, it increased with disease progression and was even strongly elevated in patients with drug-resistant and extramedullary disease. Pretreatment with dexamethasone as well as dual combination of PAT-SM6/lenalidomide further increased sGRP78 expression and consecutively showed synergistic anti-multiple myeloma effects with PAT-SM6 in proliferation assays. As proof of concept, a 62-year-old male with triple resistant multiple myeloma treated with PAT-SM6, bortezomib, and lenalidomide experienced partial remission of both intra- and extramedullary lesions. PAT-SM6 therapy in combination regimens showed efficacy in relapsed-refractory multiple myeloma. Clin Cancer Res; 22(17); 4341-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Enfermedad diarreica aguda por Escherichia coli patógenas en Colombia

PubMed Central

Gómez-Duarte, Oscar G.

2014-01-01

Resumen Las cepas de E. coli patógenas intestinales son causas importantes de la enfermedad diarreica aguda (EDA) en niños menores de 5 años en América Latina, África y Asia y están asociadas a alta mortalidad en niños en las comunidades más pobres de África y el Sudeste Asiático. Estudios sobre el papel de las E. coli patógenas intestinales en la EDA infantil en Colombia y otros países de América Latina son limitados debido a la carencia de ensayos para detección de estos patógenos en los laboratorios clínicos de centros de salud. Estudios recientes han reportado la detección de E. coli patógenas intestinales en Colombia, siendo la E. coli enterotoxigénica la cepa más frecuentemente asociada a diarrea en niños menores de 5 años. Otros patógenos detectados en estos pacientes incluyen las E. coli enteroagregativa, enteropatógena, productora de toxina Shiga, y de adherencia difusa. Con base en estudios que reportan la presencia de E. coli productora de toxina Shiga y E. coli enteroagregativa en carnes y vegetales en supermercados, se cree que productos alimentarios contaminados contribuyen a la transmisión de estos patógenos y a la infección del huésped susceptible. Más estudios son necesarios para evaluar los mecanismos de transmisión, el impacto en la epidemiologia de la EDA, y las pautas de manejo y prevención de estos patógenos que afectan la población pediátrica en Colombia. PMID:25491457

An analog of photon-assisted tunneling in a periodically modulated waveguide array

PubMed Central

Li, Liping; Luo, Xiaobing; Yang, Xiaoxue; Wang, Mei; Lü, Xinyou; Wu, Ying

2016-01-01

We theoretically report an analog of photon-assisted tunneling (PAT) originated from dark Floquet state in a periodically driven lattice array without a static biased potential by studying a three-channel waveguide system in a non-high-frequency regime. This analog of PAT can be achieved by only periodically modulating the top waveguide and adjusting the distance between the bottom and its adjacent waveguide. It is numerically shown that the PAT resonances also exist in the five-channel waveguide system and probably exist in the waveguide arrays with other odd numbers of waveguides, but they will become weak as the number of waveguides increases. With origin different from traditional PAT, this type of PAT found in our work is closely linked to the existence of the zero-energy (dark) Floquet states. It is readily observable under currently accessible experimental conditions and may be useful for controlling light propagation in waveguide arrays. PMID:27767189

Partnership for a Drug-Free America: Partnership Attitude Tracking Study. Teens: Ethnic and Racial Trends, Spring 2002.

ERIC Educational Resources Information Center

Delaney, Barbara

The annual Partnership Attitude Tracking Study (PATS) tracks consumers' attitudes about illegal drugs. PATS consists of two nationally projectable samples: a teen sample for students in grades 7-12 and a parent sample. The 2002 PATS, conducted in homes and schools, collected data using self-report surveys. Results indicate that after a decade of…

Are teachers of children and young adolescents responsive to suicide prevention training modules? Yes.

PubMed

Davidson, M W; Range, L M

1999-01-01

Both before and after a 1-hour suicide prevention training module, 75 elementary teachers-in-training read a 4-sentence vignette about a suicidal student ("Pat"), then completed 8 questions about their responses. Compared with pretraining, at post-training these teachers were more likely to say that they would send or escort Pat to the counselor's office, use written or verbal no-suicide agreements, call Pat's parents, believe Pat to be serious rather than simply seeking attention, and feel comfortable handling a similar situation. Increased proactive attitudes after one hour of training imply that teachers would benefit from periodic suicide awareness and prevention training modules.

Occurrence and Health Risk of Patulin and Pyrethroids in Fruit Juices Consumed in Bangkok, Thailand.

PubMed

Poapolathep, Saranya; Tanhan, Phanwimol; Piasai, Onuma; Imsilp, Kanjana; Hajslova, Jana; Giorgi, Mario; Kumagai, Susumu; Poapolathep, Amnart

2017-09-01

The mycotoxin patulin (PAT) is well known as a natural contaminant of apple- and other fruit-based products. Pesticides are a group of chemicals abundantly used in agriculture to maximize productivity by protecting crops from pests and weeds. Because of their harmful health effects, PAT and pesticides are strictly monitored. The current study was undertaken to investigate the significance of PAT and pyrethroid insecticide contamination in a variety of fruit juices in Bangkok. To do this, a total of 200 fruit juice samples, consisting of 40 samples each of apple, apricot, peach, pineapple, and grape juice, were collected from supermarkets in Bangkok, Thailand. PAT contamination in a variety of fruit juices was detected using validated liquid chromatography-tandem mass spectrometry, and pyrethroid insecticides (cypermethrin, cyfluthrin, and flumethrin) were analyzed using a gas chromatography equipped with micro-electron capture detector. The survey found that PAT concentrations were lower than the maximum residue limit established by European Union. The results of the present study suggest that the risk of exposure to harmful levels of PAT, cypermethrin, cyfluthrin, and flumethrin in fruit juices is very low in urban areas of Thailand.

Investigation of polymorphic transitions of piracetam induced during wet granulation.

PubMed

Potter, Catherine B; Kollamaram, Gayathri; Zeglinski, Jacek; Whitaker, Darren A; Croker, Denise M; Walker, Gavin M

2017-10-01

Piracetam was investigated as a model API which is known to exhibit a number of different polymorphic forms. It is freely soluble in water so the possibility exists for polymorphic transformations to occur during wet granulation. Analysis of the polymorphic form present during lab-scale wet granulation, using water as a granulation liquid, was studied with powder X-ray diffraction and Raman spectroscopy as off-line and inline analysis tools respectively. Different excipients with a range of hydrophilicities, aqueous solubilities and molecular weights were investigated to examine their influence on these solution-mediated polymorphic transitions and experimental results were rationalised using molecular modelling. Our results indicated that as an increasing amount of water was added to the as-received piracetam FIII, a greater amount of the API dissolved which recrystallised upon drying to the metastable FII(6.403) via a monohydrate intermediary. Molecular level analysis revealed that the observed preferential transformation of monohydrate to FII is linked with a greater structural similarity between the monohydrate and FII polymorph in comparison to FIII. The application of Raman spectroscopy as a process analytical technology (PAT) tool to monitor the granulation process for the production of the monohydrate intermediate as a precursor to the undesirable metastable form was demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

Feasibility of Raman spectroscopy as PAT tool in active coating.

PubMed

Müller, Joshua; Knop, Klaus; Thies, Jochen; Uerpmann, Carsten; Kleinebudde, Peter

2010-02-01

Active coating is a specific application of film coating where the active ingredient is comprised in the coating layer. This implementation is a challenging operation regarding the achievement of desired amount of coating and coating uniformity. To guarantee the quality of such dosage forms it is desirable to develop a tool that is able to monitor the coating operation and detect the end of the process. Coating experiments were performed at which the model drug diprophylline is coated in a pan coater on placebo tablets and tablets containing the active ingredient itself. During the active coating Raman spectra were recorded in-line. The spectral measurements were correlated with the average weight gain and the amount of coated active ingredient at each time point. The developed chemometric model was tested by monitoring further coated batches. Furthermore, the effects of pan rotation speed and working distance on the acquired Raman signal and, hence, resulting effect of the chemometric model were examined. Besides coating on placebo cores it was possible to determine the amount of active ingredient in the film when coated onto cores containing the same active ingredient. In addition, the method is even applicable when varying the process parameters and measurement conditions within a restricted range. Raman spectroscopy is an appropriate process analytical technology too.

Solid state laser communications in space (SOLACOS) high data rate satellite communication system verification program

NASA Astrophysics Data System (ADS)

Pribil, Klaus; Flemmig, Joerg

1994-09-01

This paper gives an overview on the current development status of the SOLACOS program and presents the highlights of the program. SOLACOS (Solid State Laser Communications in Space) is the national German program to develop a high performance laser communication system for high data rate transmission between LEO and GEO satellites (Inter Orbit Link, IOL). Two experimental demonstrator terminals are designed and developed in the SOLACOS program. The main development objectives are the Pointing Acquisition and Tracking subsystem (PAT) and the high data rate communication system. All key subsystems and components are straightway developed to be upgraded in follow- on projects to full space qualification. The main design objective for the system is a high degree of modularity which allows to easily upgrade the system with new upcoming technologies. Therefore, all main subsystems are interconnected via fibers to ease replacement of subsystems. The system implements an asymmetric data link with a 650 MBit/s return channel and a 10 MBit/s forward channel. The 650 MBit/s channel is based on a diode pumped Nd:YAG, Integrated Optics Modulator and uses the syncbit transmission scheme. In the syncbit system synchronization information which is necessary to maintain phase lock of the local oscillator of the coherent receiver is transmitted time multiplexed into the data stream. The PAT system comprises two beam detection sensors and three beam steering elements. For initial acquisition and tracking of the remote satellite a high speed CCD camera with an integrated image processing unit, the Acquisition and Tracking Sensor (ATS) is used. In the tacking mode the beam position is sensed via the Fibernutator sensor which is also used to couple the incoming signal into the receiver fiber. Incoming and outgoing beams are routed through the telescopes which are positioned with a 2 axis gimbal mechanism and a high speed beam steering mirror. The PAT system is controlled by a digital signal processor. For beam control advanced PAT algorithms are under development.

The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-Year Follow-Up

ERIC Educational Resources Information Center

Riddle, Mark A.; Yershova, Kseniya; Lazzaretto, Deborah; Paykina, Natalya; Yenokyan, Gayane; Greenhill, Laurence; Abikoff, Howard; Vitiello, Benedetto; Wigal, Tim; McCracken, James T.; Kollins, Scott H.; Murray, Desiree W.; Wigal, Sharon; Kastelic, Elizabeth; McGough, James J.; dosReis, Susan; Bauzo-Rosario, Audrey; Stehli, Annamarie; Posner, Kelly

2013-01-01

Objective: To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3 to 5 up to 9 to 12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS). Method: A total of 207 participants (75% male) from the original PATS, assessed at baseline (mean age,…

Design of a Pictorial Program Reference Language.

DTIC Science & Technology

1984-08-01

be fixed during the typing process. If the manuscript is given to an English teacher moonlighting as a typist, the IThe effort and expense involved in...objects with stereotyped pur- these programming cliches automatically. In the poses. These are called typical programming pat- second method, the user uses...fixed. If you gave it to alm options found in many tools today. Modeling large 0 K.glmi m teacher moonlighting as a typiA, you bodies of facts and

Integrated Cognition - A Proposed Definition of Ingredients, A Survey of Systems, and Example Architecture

DTIC Science & Technology

2004-10-01

Information Proc- essing Technology Office (IPTO) for their support of this work. We thank Dr. John Salasin for his vision in conceiving these...ingredients of cognition identified in the INCOG framework presented herein, including: Dr. John R. Anderson, Mr. Albert-Laszlo Barabasi, Dr...Goertzel, Professor Marvin Minsky, Dr. Robert Hecht-Nielsen, Dr. Marcus J. Huber, Dr. John Laird, Professor Pat Langley, Dr. Christian Lebiere, Dr

[Construction of NIRS-based process analytical system for production of salvianolic acid for injection and relative discussion].

PubMed

Zhang, Lei; Yue, Hong-Shui; Ju, Ai-Chun; Ye, Zheng-Liang

2016-10-01

Currently, near infrared spectroscopy (NIRS) has been considered as an efficient tool for achieving process analytical technology(PAT) in the manufacture of traditional Chinese medicine (TCM) products. In this article, the NIRS based process analytical system for the production of salvianolic acid for injection was introduced. The design of the process analytical system was described in detail, including the selection of monitored processes and testing mode, and potential risks that should be avoided. Moreover, the development of relative technologies was also presented, which contained the establishment of the monitoring methods for the elution of polyamide resin and macroporous resin chromatography processes, as well as the rapid analysis method for finished products. Based on author's experience of research and work, several issues in the application of NIRS to the process monitoring and control in TCM production were then raised, and some potential solutions were also discussed. The issues include building the technical team for process analytical system, the design of the process analytical system in the manufacture of TCM products, standardization of the NIRS-based analytical methods, and improving the management of process analytical system. Finally, the prospect for the application of NIRS in the TCM industry was put forward. Copyright© by the Chinese Pharmaceutical Association.

Effect of Aggressive lipid-lowering treatment with Rosuvastatin on vascular endoTHelium function: evaluation of vascular endothelium function (EARTH study).

PubMed

Takayama, Tadateru; Hiro, Takafumi; Yoda, Shunichi; Fukamachi, Daisuke; Haruta, Hironori; Kogo, Takaaki; Mineki, Takashi; Murata, Hironobu; Oshima, Toru; Hirayama, Atsushi

2018-06-01

Vascular endothelial dysfunction plays an important role in the process of atherosclerosis up to the final stage of plaque rupture. Vascular endothelial dysfunction is reversible, and can be recovered by medications and life-style changes. Improvement in endothelial function may reduce cardiovascular events and improve long-term prognosis. A total of 50 patients with stable angina and dyslipidemia were enrolled, including patients who had not received prior treatment with statins and had serum LDL-C levels ≥ 100 mg/dL, and patients who had previously received statin treatment. All agreed to register regardless of their LDL-C level. Rosuvastatin was initially administered at a dose of 2.5 mg and appropriately titrated up to the maximum dose of 20 mg or until LDL-C levels lower than 80 mg/dL were achieved, for 24 weeks. Endothelial function was assessed by the reactive hyperemia peripheral arterial tonometry (RH-PAT) index in the radial artery by Endo-PAT ® 2000 (Endo-PAT ® 2000, software version 3.0.4, Itamar Medical Ltd., Caesarea, Israel). RH-PAT data were digitally analyzed online by Endo-PAT ® 2000 at baseline and at 24 weeks. LDL-C and MDA-LDL-C decreased from 112.6 ± 23.3 to 85.5 ± 20.2 mg/dL and from 135.1 ± 36.4 to 113.9 ± 23.5 mg/dL respectively (p < 0.0001). However, HDL-C, hs-CRP and TG did not change significantly after treatment. RH-PAT index levels significantly improved, from 1.60 ± 0.31 to 1.77 ± 0.57 (p = 0.04) after treatment, and the percent change of the RH-PAT index was 12.8 ± 36.9%. Results of multivariate analysis show that serum LDL-C levels over 24 weeks did not act as a predictor of improvement of the RH-PAT index. However, HbA1c at baseline was an independent predictor which influenced the 24-week RH-PAT index level. The RH-PAT index of patients with high HbA1c at baseline did not improve after administration of rosuvastatin but it did improve in patients with low HbA1c at baseline. Aggressive lowering of LDL-C with rosuvastatin significantly improved the RH-PAT index, suggesting that it may improve endothelial function in patients with coronary artery disease.Clinical Trial Registration No: UMIN-CTR, UMIN000010040.

[Geriatric Proximal Femoral Fracture and Urinary Tract Infection - Considerations for Perioperative Infection Prophylaxis].

PubMed

Probst, A; Reimers, N; Hecht, A; Langenhan, R

2016-10-01

Background: Perioperative infection prophylaxis with cephalosporins is standard in surgical treatment of proximal femoral fractures (PFF). Geriatric patients (pat.) are at risk of chronic infections and the bacteria from these can lead to unknown hygienic problems in an early operation. We therefore characterised the colonisation of the urinary tract in pat. (≥ 65 years) with PFF and observed bacterial development in deep wound infections over a period of 10 years. The aim was to discover gaps in perioperative infection prophylaxis. Patients and Methods: Between September 2013 and November 2015, colonisation of the urinary tract and microbial resistance were investigated on admission of all pat. (≥ 65 years) with the diagnosis of PFF (n = 351; f/m 263/88; median age [∅] 83.57 [65-100] years). Between 2005 and 2014, 2161 pat. with a PFF were operated in our clinic (f/m 1623/538; ∅ 82.35 [65-101] years). 991 pat. (∅ 81.84 [65-101] years) with femoral neck fracture [FNF] were treated with endoprosthesis/osteosynthesis, 1170 pat. (∅ 82,78 [65-101] years) with per-/subtrochanteric fracture [PTF] were treated with osteosynthesis. In a retrospective data analysis, deep wound infections, microbiological composition and changes in microbial resistances over time were identified. Results: Bacteriuria (BU) was detected in the urine sediment of 35.61 % (n = 125) of our pat. In 47.2 % of these pat., BU was accompanied by laboratory signs of manifest urinary tract infection. In 10.4 % of these pat., colonisation of the urinary tract with multi-resistant pathogens was detected; 26.4 % were resistant to cefuroxime. The rate of deep infections in pat. with endoprosthesis/osteosynthesis in FNF was 2.8 % (n = 28; f/m 19/9; ∅ 81.35 [67-92] years), with osteosynthesis in PTF 1,1 % (n = 14; f/m 10/4; ∅ 81.0 [70-91] years). A comparison of the periods 2005-2009 and 2010-2014 showed a shift in the spectrum of pathogens from cephalosporin-sensitive to cephalosporin-resistant enterococci. Resistance of pathogens against cephalosporins increased from 43 to 81 %. Conclusion: We found an increasing risk in geriatric pat. from multiresistant pathogens in the urinary tract and from an increase in the cephalosporin resistance of pathogens in urinary tract infections and in deep wound infections. This indicates that perioperative infection prophylaxis with a cephalosporin is not effective. Especially in nursing homes, development of resistance to antibiotics is an increasing problem. Thus, concepts of perioperative infection prophylaxis in geriatric patients should be reconsidered. Georg Thieme Verlag KG Stuttgart · New York.

Overview of the High Performance Antiproton Trap (HiPAT) Experiment

NASA Technical Reports Server (NTRS)

Martin, James; Chakrabarti, Suman; Pearson, Boise; Sims, W. Herbert; Lewis, Raymond; Fant, Wallace; Rodgers, Stephen (Technical Monitor)

2002-01-01

A general overview of the High Performance Antiproton Trap (HiPAT) Experiment is presented. The topics include: 1) Why Antimatter? 2) HiPAT Applicability; 3) Approach-Goals; 4) HiPAT General Layout; 5) Sizing For Containment; 6) Laboratory Operations; 7) Vacuum System Cleaning; 8) Ion Production Via Electron Gun; 9) Particle Capture Via Ion Sources; 10) Ion Beam Steering/Focusing; 11) Ideal Ion Stacking Sequence; 12) Setup For Dynamic Capture; 13) Dynamic Capture of H(+) Ions; 14) Dynamic Capture; 15) Radio Frequency Particle Detection; 16) Radio Frequency Antenna Modeling; and 17) R.F. Stabilization-Low Frequencies. A short presentation of propulsion applications of Antimatter is also given. This paper is in viewgraph form.

Biocontrol activity and patulin-removal effects of Bacillus subtilis, Rhodobacter sphaeroides and Agrobacterium tumefaciens against Penicillium expansum.

PubMed

Wang, Y; Yuan, Y; Liu, B; Zhang, Z; Yue, T

2016-11-01

This study was conducted to evaluate the biocontrol potential of Bacillus subtilis CICC 10034, Rhodobacter sphaeroides CGMCC 1.2182 and Agrobacterium tumefaciens CGMCC 1.2554 against patulin (PAT)-producer Penicillium expansum and their ability to remove PAT. Bacillus subtilis effectively inhibited P. expansum both on apples and in in vitro experiments, which reduced the rot diameter on apples by 38% compared with the control. The reduction was followed by those induced by A. tumefaciens (27·63%) and R. sphaeroides (23·67%). None of the cell-free supernatant (CFS) was able to prevent pathogen growth. Three antagonists could suppress PAT production by P. expansum on apples by 98·5, 93·7 and 94·99% after treatment with B. subtilis, R. sphaeroides and A. tumefaciens respectively. In addition, the three strains led to a 0·56-1·47 log CFU g -1 reduction in colony number of P. expansum on apples. Survival of antagonists on apple wounds revealed their tolerance to PAT. Furthermore, both live and autoclaved cells of three strains efficiently adsorbed artificially spiked PAT from medium. The selected antagonists could be applied before harvesting to control apple infection by PAT-producing fungi and also during processing to act as PAT detoxifiers. Since little information related to the capability of R. sphaeroides and A. tumefaciens to inhibit P. expansum is currently available, the results of this study provide some new perspectives to the biocontrol field. © 2016 The Society for Applied Microbiology.

Patulin in domestic and imported apple-based drinks in Belgium: occurrence and exposure assessment.

PubMed

Tangni, E K; Theys, R; Mignolet, E; Maudoux, M; Michelet, J Y; Larondelle, Y

2003-05-01

Apple-based beverages are regularly consumed by adults and children in Belgium. They are locally produced or imported from other countries. The apples used as starting material for these productions are frequently contaminated by mycotoxin-producing moulds and damaged during transport and handling. The current study was undertaken to investigate whether patulin (PAT) is present in the industrial or handicraft-made apple juices and ciders consumed by the Belgian population and to assess the population's exposure to this mycotoxin through apple-based drinks. Belgian (n = 29) and imported (14) apple juices as well as ciders (7) were assayed for PAT by high-performance liquid chromatography with ultraviolet light detection. PAT was detected respectively in 79, 86 and 43% of these tested samples. However, no contaminated sample exceeded the safe level of 50 microg PAT l(-1). Levels of PAT contamination were comparable in Belgian and imported juice samples. The overall mean PAT concentrations were 9.0 and 3.4 microg l(-1) for contaminated apple juices and ciders, respectively. This study also indicates that there was no statistically significant difference in the mean PAT contamination between clear (7.8 microg l(-1)) and cloudy (10.7 microg l(-1)) apple juices, as well as between handicraft-made apple juices (14.6 microg l(-1)) and industrial ones (7.0 microg l(-1)). On the basis of the mean results, a consumer exposure assessment indicates that a daily intake of 0.2 litres apple juice contributes to 45% of the provisional maximum tolerable daily intake for a child of 10 kg body weight.

The structural hinge of a chain-foreland basin: Quaternary activity of the Pede-Apennine Thrust front (Northern Italy)

NASA Astrophysics Data System (ADS)

Maestrelli, Daniele; Benvenuti, Marco; Bonini, Marco; Carnicelli, Stefano; Piccardi, Luigi; Sani, Federico

2018-01-01

The Pede-Apennine margin (Northern Italy) is a major WNW-ESE-trending morpho-structural element that delimits the Po Plain to the southwest and consists of a system of southwest dipping thrusts, generally referred to as Pede-Apennine Thrust (PAT). The leading edge of the chain lies further north-east and is buried beneath the Plio-Quaternary marine and fluvial deposits of the Po Plain. Whereas the buried external thrust fronts are obvious active structures (as demonstrated by the 2012 Emilia earthquakes; e.g. Burrato et al., 2012), ongoing activity of the PAT is debated. Using a multidisciplinary approach that integrates structural, seismic, sedimentological and pedological field data, we describe the recent activity of the PAT structures in a sector of the Pede-Apennine margin between the Panaro and the Enza Rivers (Emilia-Romagna). We found that the PAT is emergent or sub-emergent and deforms Middle Pleistocene deposits. We also infer a more recent tectonic phase ( 60-80 ka) by Optically Stimulated Luminescence (OSL) dating of soil profiles that have been deformed by a recent reactivation of the PAT. Furthermore, we show evidence that the PAT and its external splay thrusts strongly influenced the drainage pattern, causing fluvial diversions and forcing paleo-rivers to develop roughly parallel to the margin. Finally, numerical Trishear modelling has been used to calculate deformation rates for the PAT along two transects. Extrapolated slip rates vary between 0.68 and 0.79 mm·yr- 1 for about the last 1.2-0.8 million years.

Biocontrol Agents Increase the Specific Rate of Patulin Production by Penicillium expansum but Decrease the Disease and Total Patulin Contamination of Apples

PubMed Central

Zheng, Xiangfeng; Yang, Qiya; Zhang, Xiaoyun; Apaliya, Maurice T.; Ianiri, Giuseppe; Zhang, Hongyin; Castoria, Raffaello

2017-01-01

Synthetic fungicides are commonly employed for the control of postharvest diseases of fruits. However, due to health concerns about the use of these chemicals, alternative control methods including biocontrol based on antagonistic yeasts are gaining in popularity. In this study, we investigated the effects of two biocontrol yeasts, Rhodotorula mucilaginosa strain 3617 and Rhodotorula kratochvilovae strain LS11, on blue mold and patulin (PAT) contamination caused by Penicillium expansum strains PY and FS7 in artificially inoculated Fuji apples stored at 20°C for 9 days. To correlate the development of the P. expansum strains in yeast-treated and untreated apples with PAT production, we quantified their biomass in the infected fruits using a recently published quantitative real-time polymerase chain reaction method based on specific primers for patF, a gene from P. expansum that is involved in PAT biosynthesis. Both yeasts significantly reduced the disease incidence caused by the two strains of P. expansum up to 5–7 days of incubation, and lowered their biomass and the progression of symptoms up to 9 days. Interestingly, both yeasts strains increased the rate of PAT production (expressed as ng patulin/μg fungal DNA) by the two pathogenic strains. Nevertheless, both biocontrol agents reduced the total PAT contamination, especially in the case of P. expansum strain FS7, the higher PAT producer of the two tested P. expansum strains. Comparing between the yeast strains, R. kratochvilovae LS11 was more effective than R. mucilaginosa 3617 for the control of P. expansum. PMID:28713362

Photoacoustic tomography of joints aided by an Etanercept-conjugated gold nanoparticle contrast agent—an ex vivo preliminary rat study

NASA Astrophysics Data System (ADS)

Chamberland, David L.; Agarwal, Ashish; Kotov, Nicholas; Fowlkes, J. Brian; Carson, Paul L.; Wang, Xueding

2008-03-01

Monitoring of anti-rheumatic drug delivery in experimental models and in human diseases would undoubtedly be very helpful for both basic research and clinical management of inflammatory diseases. In this study, we have investigated the potential of an emerging hybrid imaging technology—photoacoustic tomography—in noninvasive monitoring of anti-TNF drug delivery. After the contrast agent composed of gold nanorods conjugated with Etanercept molecules was produced, ELISA experiments were performed to prove the conjugation and to show that the conjugated anti-TNF-α drug was biologically active. PAT of ex vivo rat tail joints with the joint connective tissue enhanced by intra-articularly injected contrast agent was conducted to examine the performance of PAT in visualizing the distribution of the gold-nanorod-conjugated drug in articular tissues. By using the described system, gold nanorods with a concentration down to 1 pM in phantoms or 10 pM in biological tissues can be imaged with good signal-to-noise ratio and high spatial resolution. This study demonstrates the feasibility of conjugating TNF antagonist pharmaceutical preparations with gold nanorods, preservation of the mechanism of action of TNF antagonist along with preliminary evaluation of novel PAT technology in imaging optical contrast agents conjugated with anti-rheumatic drugs. Further in vivo studies on animals are warranted to test the specific binding between such conjugates and targeted antigen in joint tissues affected by inflammation.

Patulin causes DNA damage leading to cell cycle arrest and apoptosis through modulation of Bax, p{sup 53} and p{sup 21/WAF1} proteins in skin of mice

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

Saxena, Neha; Ansari, Kausar M.; Kumar, Rahul

2009-01-15

Patulin (PAT), a mycotoxin found in apples, grapes, oranges, pear and peaches, is a potent genotoxic compound. WHO has highlighted the need for the study of cutaneous toxicity of PAT as manual labour is employed during pre and post harvest stages, thereby causing direct exposure to skin. In the present study cutaneous toxicity of PAT was evaluated following topical application to Swiss Albino mice. Dermal exposure of PAT, to mice for 4 h resulted in a dose (40-160 {mu}g/animal) and time (up to 6 h) dependent enhancement of ornithine decarboxylase (ODC), a marker enzyme of cell proliferation. The ODC activitymore » was found to be normal after 12 and 24 h treatment of patulin. Topical application of PAT (160 {mu}g/100 {mu}l acetone) for 24-72 h caused (a) DNA damage in skin cells showing significant increase (34-63%) in olive tail moment, a parameter of Comet assay (b) significant G 1 and S-phase arrest along with induction of apoptosis (2.8-10 folds) as shown by annexin V and PI staining assay through flow cytometer. Moreover PAT leads to over expression of p{sup 21/WAF1} (3.6-3.9 fold), pro apoptotic protein Bax (1.3-2.6) and tumor suppressor wild type p{sup 53} (2.8-3.9 fold) protein. It was also shown that PAT induced apoptosis was mediated through mitochondrial intrinsic pathway as revealed through the release of cytochrome C protein in cytosol leading to enhancement of caspase-3 activity in skin cells of mice. These results suggest that PAT has a potential to induce DNA damage leading to p{sup 53} mediated cell cycle arrest along with intrinsic pathway mediated apoptosis that may also be correlated with enhanced polyamine production as evident by induction of ODC activity, which may have dermal toxicological implications.« less

Dose-related antihyperglycemic and hypolipidemic effects of two novel thiazolidin-4-ones in a rodent model of metabolic syndrome.

PubMed

Karot, Sarine Sebastian; Surenahalli, Vasantharaju Gowdra; Kishore, Anoop; Mudgal, Jayesh; Nandakumar, Krishnadas; Chirayil, Magith Thambi; Mathew, Geetha; Nampurath, Gopalan Kutty

2016-09-01

The replacement of the thiazolidinedione moiety with a thiazolidinone may yield antidiabetic compounds with similar pleiotropic effects. Hence, the aim of the present study was to explore the dose-related antihyperglycemic and hypolipidemic effects of two synthesized novel thiazolidin-4-one derivatives, one with a nicotinamide and the other with a p-chlorophenoxyacetamide substitution at the N3 position of the thiazolidinone ring (NAT1 and PAT1, respectively), in a rodent model of metabolic syndrome (MetS). Metabolic syndrome was induced in Wistar rats by neonatal administration of monosodium glutamate (i.p.) on 4 consecutive days followed by high-sucrose diet feeding for 6 months. The effects of NAT1 (33 and 66 mg/kg) and molar equivalent doses of PAT1 (40 and 80 mg/kg) on relevant biochemical parameters were evaluated. Because MetS is a state of chronic low-grade inflammation, we also evaluated the effects of these compounds on proinflammatory markers, namely interleukin (IL)-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and nitric oxide (NO). Both NAT1 and PAT1 attenuated hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, and glucose intolerance. PAT1 exhibited superior antihyperglycemic and antihypoalphalipoproteinemic effects than NAT1. However, NAT1 had a better triglyceride-lowering effect. At the lower dose tested, both compounds significantly reduced elevated malondialdehyde levels. In addition, PAT1 (80 mg/kg) restored hepatic superoxide dismutase enzyme levels. There was a tendency for NAT1 and PAT1 to inhibit elevated hepatic IL-6 and TNF-α levels, but the differences did not reach statistical significance. In addition, PAT1 exhibited in vitro anti-inflammatory activity by reducing proinflammatory ROS and NO levels in RAW264.7 macrophages. The novel thiazolidin-4-ones NAT1 and PAT1 could be potential pleiotropic drug candidates targeting MetS. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Development of a Psychosocial Risk Screener for Siblings of Children With Cancer: Incorporating the Perspectives of Parents.

PubMed

Long, Kristin A; Pariseau, Emily M; Muriel, Anna C; Chu, Andrea; Kazak, Anne E; Alderfer, Melissa A

2018-04-03

Although many siblings experience distress after a child's cancer diagnosis, their psychosocial functioning is seldom assessed in clinical oncology settings. One barrier to systematic sibling screening is the lack of a validated, sibling-specific screening instrument. Thus, this study developed sibling-specific screening modules in English and Spanish for the Psychosocial Assessment Tool (PAT), a well-validated screener of family psychosocial risk. A purposive sample of English- and Spanish-speaking parents of children with cancer (N = 29) completed cognitive interviews to provide in-depth feedback on the development of the new PAT sibling modules. Interviews were transcribed verbatim, cleaned, and analyzed using applied thematic analysis. Items were updated iteratively according to participants' feedback. Data collection continued until saturation was reached (i.e., all items were clear and valid). Two sibling modules were developed to assess siblings' psychosocial risk at diagnosis (preexisting risk factors) and several months thereafter (reactions to cancer). Most prior PAT items were retained; however, parents recommended changes to improve screening format (separately assessing each sibling within the family and expanding response options to include "sometimes"), developmental sensitivity (developing or revising items for ages 0-2, 3-4, 5-9, and 10+ years), and content (adding items related to sibling-specific social support, global assessments of sibling risk, emotional/behavioral reactions to cancer, and social ecological factors such as family and school). Psychosocial screening requires sibling-specific screening items that correspond to preexisting risk (at diagnosis) and reactions to cancer (several months after diagnosis). Validated, sibling-specific screeners will facilitate identification of siblings with elevated psychosocial risk.

Typhoons Pat and Odessa in the Western Pacific Ocean

NASA Image and Video Library

1985-08-30

51I-35-078 (30 Aug 1985) --- Typhoons Pat (left) and Odessa in the western Pacific. Of the many tropical cyclones photographed by the STS 51-I crew, the dual typhoons of Pat and Odessa were the most unusual. The twin typhoons constitute a Fujiwara system of connected cyclones first described by the Japanese meteorologist after whom the phenomena has been named. Never before have such paired typhoons been photographed from orbit.

Tutorial on photoacoustic tomography

PubMed Central

Zhou, Yong; Yao, Junjie; Wang, Lihong V.

2016-01-01

Abstract. Photoacoustic tomography (PAT) has become one of the fastest growing fields in biomedical optics. Unlike pure optical imaging, such as confocal microscopy and two-photon microscopy, PAT employs acoustic detection to image optical absorption contrast with high-resolution deep into scattering tissue. So far, PAT has been widely used for multiscale anatomical, functional, and molecular imaging of biological tissues. We focus on PAT’s basic principles, major implementations, imaging contrasts, and recent applications. PMID:27086868

RAND’s Portfolio Analysis Tool (PAT): Theory, Methods, and Reference Manual

DTIC Science & Technology

2009-01-01

language , such as Analytica® (a product of Lumina Decision Systems, Inc., [www.lumina.com]). We used such a connection approach in our work for MDA...with $ signs ) so that the formulas will be automatically adjusted if they change PAT’s structure by, e.g., adding a column or row. Checking is...year, in real (inflation-protected) dollars. The sign is positive or negative, depending on whether one is receiving or paying and on the syntax of

Pulse Shape Correlation for Laser Detection and Ranging (LADAR)

DTIC Science & Technology

2010-03-01

with the incoming measured laser pulse [3]. All of these shapes are symmetric. Siegman and Liu’s findings indicate that the pulse is seldom symmetric...of Engineering, Air Force Institute of Technology (AETC), Wright Pat- terson AFB, OH, March 2007. 10. Siegman , Anthony E. Lasers . University Science...Pulse Shape Correlation for Laser Detection and Ranging (LADAR) THESIS Brian T. Deas, Major, USAF AFIT/GE/ENG/10-07 DEPARTMENT OF THE AIR FORCE AIR

Increased prenatal IGF2 expression due to the porcine intron3-G3072A mutation may be responsible for increased muscle mass.

PubMed

Clark, D L; Clark, D I; Beever, J E; Dilger, A C

2015-05-01

A SNP (IGF2 G3072A) within intron 3 of disrupts a binding site for the repressor zinc finger BED-type containing 6 (ZBED6), leading to increased carcass lean yields in pigs. However, the relative contributions of prenatal as opposed to postnatal increased IGF2 expression are unclear. As muscle fiber number is set at birth, prenatal and neonate skeletal muscle development is critical in determining mature growth potential. Therefore, the objectives of this study were to determine the contributions of hyperplasia and hypertrophy to increased muscle mass and to delineate the effect of the mutation on the expression of myogenic genes during prenatal and postnatal growth. Sows (IGF2 A/A) were bred to a single heterozygous (IGF2 A/G) boar. For fetal samples, sows were euthanized at 60 and 90 d of gestation (d60 and d90) to obtain fetuses. Male and female offspring were also euthanized at birth (0d), weaning (21d), and market weight of approximately 130 kg (176d). At each sampling time, the LM, psoas major (PM), and semitendinosus (ST) muscles were weighed. Samples of the LM were used to quantify the expression of IGF family members, myogenic regulatory factors (MRF), myosin heavy chain isoforms, and growth factors, myostatin, and . Liver samples were used to quantify and expression. At 176d, weights of LM, PM, and ST muscles were all increased approximately 8% to 14% (P < 0.01) in pigs with paternal A (A(Pat)) alleles compared with those with paternal G (G(Pat)) alleles. Additionally, total muscle fiber number in the ST at 176d tended to be greater (P = 0.10), whereas muscle fiber cross-sectional area tended to be reduced ( P= 0.08) in A(Pat) pigs compared with G(Pat) pigs. In addition to the expected 2.7- to 4.5-fold increase (P ≤ 0.02) in expression in the LM in A(Pat) compared with G(Pat) pigs at postnatal sampling times (21d and 176d), IGF2 expression was also increased (P ≤ 0.06) 1.4- to 1.5-fold at d90 of gestation and at birth. At d90, expression of myogenic factor 5 (MYF5), a MRF expressed in proliferating myoblasts, in the LM was greater (P = 0.01) in A (Pat) pigs than in G(Pat) pigs. Interestingly, at 21d hepatic expression was greater (P = 0.01), whereas expression decreased (P = 0.01) in A(Pat) pigs compared with G(Pat) pigs; however, there were no differences (P ≥ 0.18) in hepatic expression between genotypes at 0d and 176d. These data suggest that prenatal hyperplasia of muscle fibers stimulated by increased IGF2 expression may contribute to increased muscle mass of A(Pat) pigs.

Analytical quality by design: a tool for regulatory flexibility and robust analytics.

PubMed

Peraman, Ramalingam; Bhadraya, Kalva; Padmanabha Reddy, Yiragamreddy

2015-01-01

Very recently, Food and Drug Administration (FDA) has approved a few new drug applications (NDA) with regulatory flexibility for quality by design (QbD) based analytical approach. The concept of QbD applied to analytical method development is known now as AQbD (analytical quality by design). It allows the analytical method for movement within method operable design region (MODR). Unlike current methods, analytical method developed using analytical quality by design (AQbD) approach reduces the number of out-of-trend (OOT) results and out-of-specification (OOS) results due to the robustness of the method within the region. It is a current trend among pharmaceutical industry to implement analytical quality by design (AQbD) in method development process as a part of risk management, pharmaceutical development, and pharmaceutical quality system (ICH Q10). Owing to the lack explanatory reviews, this paper has been communicated to discuss different views of analytical scientists about implementation of AQbD in pharmaceutical quality system and also to correlate with product quality by design and pharmaceutical analytical technology (PAT).

Analytical Quality by Design: A Tool for Regulatory Flexibility and Robust Analytics

PubMed Central

Bhadraya, Kalva; Padmanabha Reddy, Yiragamreddy

2015-01-01

Very recently, Food and Drug Administration (FDA) has approved a few new drug applications (NDA) with regulatory flexibility for quality by design (QbD) based analytical approach. The concept of QbD applied to analytical method development is known now as AQbD (analytical quality by design). It allows the analytical method for movement within method operable design region (MODR). Unlike current methods, analytical method developed using analytical quality by design (AQbD) approach reduces the number of out-of-trend (OOT) results and out-of-specification (OOS) results due to the robustness of the method within the region. It is a current trend among pharmaceutical industry to implement analytical quality by design (AQbD) in method development process as a part of risk management, pharmaceutical development, and pharmaceutical quality system (ICH Q10). Owing to the lack explanatory reviews, this paper has been communicated to discuss different views of analytical scientists about implementation of AQbD in pharmaceutical quality system and also to correlate with product quality by design and pharmaceutical analytical technology (PAT). PMID:25722723

Development and Validation of a Multiplexed Protein Quantitation Assay for the Determination of Three Recombinant Proteins in Soybean Tissues by Liquid Chromatography with Tandem Mass Spectrometry.

PubMed

Hill, Ryan C; Oman, Trent J; Shan, Guomin; Schafer, Barry; Eble, Julie; Chen, Cynthia

2015-08-26

Currently, traditional immunochemistry technologies such as enzyme-linked immunosorbent assays (ELISA) are the predominant analytical tool used to measure levels of recombinant proteins expressed in genetically engineered (GE) plants. Recent advances in agricultural biotechnology have created a need to develop methods capable of selectively detecting and quantifying multiple proteins in complex matrices because of increasing numbers of transgenic proteins being coexpressed or "stacked" to achieve tolerance to multiple herbicides or to provide multiple modes of action for insect control. A multiplexing analytical method utilizing liquid chromatography with tandem mass spectrometry (LC-MS/MS) has been developed and validated to quantify three herbicide-tolerant proteins in soybean tissues: aryloxyalkanoate dioxygenase (AAD-12), 5-enol-pyruvylshikimate-3-phosphate synthase (2mEPSPS), and phosphinothricin acetyltransferase (PAT). Results from the validation showed high recovery and precision over multiple analysts and laboratories. Results from this method were comparable to those obtained with ELISA with respect to protein quantitation, and the described method was demonstrated to be suitable for multiplex quantitation of transgenic proteins in GE crops.

Mark report satellite tags (mrPATs) to detail large-scale horizontal movements of deep water species: First results for the Greenland shark (Somniosus microcephalus)

NASA Astrophysics Data System (ADS)

Hussey, Nigel E.; Orr, Jack; Fisk, Aaron T.; Hedges, Kevin J.; Ferguson, Steven H.; Barkley, Amanda N.

2018-04-01

The deep-sea is increasingly viewed as a lucrative environment for the growth of resource extraction industries. To date, our ability to study deep-sea species lags behind that of those inhabiting the photic zone limiting scientific data available for management. In particular, knowledge of horizontal movements is restricted to two locations; capture and recapture, with no temporal information on absolute animal locations between endpoints. To elucidate the horizontal movements of a large deep-sea fish, a novel tagging approach was adopted using the smallest available prototype satellite tag - the mark-report pop-up archival tag (mrPAT). Five Greenland sharks (Somniosus microcephalus) were equipped with multiple mrPATs as well as a standard archival satellite tag (miniPAT) that were programmed to release in sequence at 8-10 day intervals. The performance of the mrPATs was quantified. The tagging approach provided multiple locations per individual and revealed a previously unknown directed migration of Greenland sharks from the Canadian high Arctic to Northwest Greenland. All tags reported locations, however, the accuracy and time from expected release were variable among tags (average time to an accurate location from expected release = 30.8 h, range: 4.9-227.6 h). Average mrPAT drift rate estimated from best quality messages (LQ1,2,3) was 0.37 ± 0.09 m/s indicating tags were on average 41.1 ± 63.4 km (range: 6.5-303.1 km) from the location of the animal when they transmitted. mrPATs provided daily temperature values that were highly correlated among tags and with the miniPAT (70.8% of tag pairs were significant). In contrast, daily tilt sensor data were variable among tags on the same animal (12.5% of tag pairs were significant). Tracking large-scale movements of deep-sea fish has historically been limited by the remote environment they inhabit. The current study provides a new approach to document reliable coarse scale horizontal movements to understand migrations, stock structure and habitat use of large species. Opportunities to apply mrPATs to understand the movements of medium size fish, marine mammals and to validate retrospective movement modeling approaches based on archival data are presented.

Radiation Detection Center on the Front Lines

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

Hazi, A

2005-09-20

Many of today's radiation detection tools were developed in the 1960s. For years, the Laboratory's expertise in radiation detection resided mostly within its nuclear test program. When nuclear testing was halted in the 1990s, many of Livermore's radiation detection experts were dispersed to other parts of the Laboratory, including the directorates of Chemistry and Materials Science (CMS); Physics and Advanced Technologies (PAT); Defense and Nuclear Technologies (DNT); and Nonproliferation, Arms Control, and International Security (NAI). The RDC was formed to maximize the benefit of radiation detection technologies being developed in 15 to 20 research and development (R&D) programs. These effortsmore » involve more than 200 Laboratory employees across eight directorates, in areas that range from electronics to computer simulations. The RDC's primary focus is the detection, identification, and analysis of nuclear materials and weapons. A newly formed outreach program within the RDC is responsible for conducting radiation detection workshops and seminars across the country and for coordinating university student internships. Simon Labov, director of the RDC, says, ''Virtually all of the Laboratory's programs use radiation detection devices in some way. For example, DNT uses radiation detection to create radiographs for their work in stockpile stewardship and in diagnosing explosives; CMS uses it to develop technology for advancing the detection, diagnosis, and treatment of cancer; and the Energy and Environment Directorate uses radiation detection in the Marshall Islands to monitor the aftermath of nuclear testing in the Pacific. In the future, the National Ignition Facility will use radiation detection to probe laser targets and study shock dynamics.''« less

Objective Assessment and Design Improvement of a Staring, Sparse Transducer Array by the Spatial Crosstalk Matrix for 3D Photoacoustic Tomography

PubMed Central

Kosik, Ivan; Raess, Avery

2015-01-01

Accurate reconstruction of 3D photoacoustic (PA) images requires detection of photoacoustic signals from many angles. Several groups have adopted staring ultrasound arrays, but assessment of array performance has been limited. We previously reported on a method to calibrate a 3D PA tomography (PAT) staring array system and analyze system performance using singular value decomposition (SVD). The developed SVD metric, however, was impractical for large system matrices, which are typical of 3D PAT problems. The present study consisted of two main objectives. The first objective aimed to introduce the crosstalk matrix concept to the field of PAT for system design. Figures-of-merit utilized in this study were root mean square error, peak signal-to-noise ratio, mean absolute error, and a three dimensional structural similarity index, which were derived between the normalized spatial crosstalk matrix and the identity matrix. The applicability of this approach for 3D PAT was validated by observing the response of the figures-of-merit in relation to well-understood PAT sampling characteristics (i.e. spatial and temporal sampling rate). The second objective aimed to utilize the figures-of-merit to characterize and improve the performance of a near-spherical staring array design. Transducer arrangement, array radius, and array angular coverage were the design parameters examined. We observed that the performance of a 129-element staring transducer array for 3D PAT could be improved by selection of optimal values of the design parameters. The results suggested that this formulation could be used to objectively characterize 3D PAT system performance and would enable the development of efficient strategies for system design optimization. PMID:25875177

Analysis of the potential for non-invasive imaging of oxygenation at heart depth, using ultrasound optical tomography (UOT) or photo-acoustic tomography (PAT).

PubMed

Walther, Andreas; Rippe, Lars; Wang, Lihong V; Andersson-Engels, Stefan; Kröll, Stefan

2017-10-01

Despite the important medical implications, it is currently an open task to find optical non-invasive techniques that can image deep organs in humans. Addressing this, photo-acoustic tomography (PAT) has received a great deal of attention in the past decade, owing to favorable properties like high contrast and high spatial resolution. However, even with optimal components PAT cannot penetrate beyond a few centimeters, which still presents an important limitation of the technique. Here, we calculate the absorption contrast levels for PAT and for ultrasound optical tomography (UOT) and compare them to their relevant noise sources as a function of imaging depth. The results indicate that a new development in optical filters, based on rare-earth-ion crystals, can push the UOT technique significantly ahead of PAT. Such filters allow the contrast-to-noise ratio for UOT to be up to three orders of magnitude better than for PAT at depths of a few cm into the tissue. It also translates into a significant increase of the image depth of UOT compared to PAT, enabling deep organs to be imaged in humans in real time. Furthermore, such spectral holeburning filters are not sensitive to speckle decorrelation from the tissue and can operate at nearly any angle of incident light, allowing good light collection. We theoretically demonstrate the improved performance in the medically important case of non-invasive optical imaging of the oxygenation level of the frontal part of the human myocardial tissue. Our results indicate that further studies on UOT are of interest and that the technique may have large impact on future directions of biomedical optics.

The relation of digital vascular function to cardiovascular risk factors in African-Americans using digital tonometry: the Jackson Heart Study.

PubMed

McClendon, Eric E; Musani, Solomon K; Samdarshi, Tandaw E; Khaire, Sushant; Stokes, Donny; Hamburg, Naomi M; Sheffy, Koby; Mitchell, Gary F; Taylor, Herman R; Benjamin, Emelia J; Fox, Ervin R

2017-06-01

Digital vascular tone and function, as measured by peripheral arterial tonometry (PAT), are associated with cardiovascular risk and events in non-Hispanic whites. There are limited data on relations between PAT and cardiovascular risk in African-Americans. PAT was performed on a subset of Jackson Heart Study participants using a fingertip tonometry device. Resting digital vascular tone was assessed as baseline pulse amplitude. Hyperemic vascular response to 5 minutes of ischemia was expressed as the PAT ratio (hyperemic/baseline amplitude ratio). Peripheral augmentation index (AI), a measure of relative wave reflection, also was estimated. The association of baseline pulse amplitude (PA), PAT ratio, and AI to risk factors was assessed using stepwise multivariable models. The study sample consisted of 837 participants from the Jackson Heart Study (mean age, 54 ± 11 years; 61% women). In stepwise multivariable regression models, baseline pulse amplitude was related to male sex, body mass index, and diastolic blood pressure (BP), accounting for 16% of the total variability of the baseline pulse amplitude. Age, male sex, systolic BP, diastolic BP, antihypertensive medication, and prevalent cardiovascular disease contributed to 11% of the total variability of the PAT ratio. Risk factors (primarily age, sex, and heart rate) explained 47% of the total variability of the AI. We confirmed in our cohort of African-Americans, a significant relation between digital vascular tone and function measured by PAT and multiple traditional cardiovascular risk factors. Further studies are warranted to investigate the utility of these measurements in predicting clinical outcomes in African-Americans. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Detecting REM sleep from the finger: an automatic REM sleep algorithm based on peripheral arterial tone (PAT) and actigraphy.

PubMed

Herscovici, Sarah; Pe'er, Avivit; Papyan, Surik; Lavie, Peretz

2007-02-01

Scoring of REM sleep based on polysomnographic recordings is a laborious and time-consuming process. The growing number of ambulatory devices designed for cost-effective home-based diagnostic sleep recordings necessitates the development of a reliable automatic REM sleep detection algorithm that is not based on the traditional electroencephalographic, electrooccolographic and electromyographic recordings trio. This paper presents an automatic REM detection algorithm based on the peripheral arterial tone (PAT) signal and actigraphy which are recorded with an ambulatory wrist-worn device (Watch-PAT100). The PAT signal is a measure of the pulsatile volume changes at the finger tip reflecting sympathetic tone variations. The algorithm was developed using a training set of 30 patients recorded simultaneously with polysomnography and Watch-PAT100. Sleep records were divided into 5 min intervals and two time series were constructed from the PAT amplitudes and PAT-derived inter-pulse periods in each interval. A prediction function based on 16 features extracted from the above time series that determines the likelihood of detecting a REM epoch was developed. The coefficients of the prediction function were determined using a genetic algorithm (GA) optimizing process tuned to maximize a price function depending on the sensitivity, specificity and agreement of the algorithm in comparison with the gold standard of polysomnographic manual scoring. Based on a separate validation set of 30 patients overall sensitivity, specificity and agreement of the automatic algorithm to identify standard 30 s epochs of REM sleep were 78%, 92%, 89%, respectively. Deploying this REM detection algorithm in a wrist worn device could be very useful for unattended ambulatory sleep monitoring. The innovative method of optimization using a genetic algorithm has been proven to yield robust results in the validation set.

Combined multimodal photoacoustic tomography, optical coherence tomography (OCT) and OCT based angiography system for in vivo imaging of multiple skin disorders in human(Conference Presentation)

NASA Astrophysics Data System (ADS)

Liu, Mengyang; Chen, Zhe; Sinz, Christoph; Rank, Elisabet; Zabihian, Behrooz; Zhang, Edward Z.; Beard, Paul C.; Kittler, Harald; Drexler, Wolfgang

2017-02-01

All optical photoacoustic tomography (PAT) using a planar Fabry-Perot interferometer polymer film sensor has been demonstrated for in vivo human palm imaging with an imaging penetration depth of 5 mm. The relatively larger vessels in the superficial plexus and the vessels in the dermal plexus are visible in PAT. However, due to both resolution and sensitivity limits, all optical PAT cannot reveal the smaller vessels such as capillary loops and venules. Melanin absorption also sometimes causes difficulties in PAT to resolve vessels. Optical coherence tomography (OCT) based angiography, on the other hand, has been proven suitable for microvasculature visualization in the first couple millimeters in human. In our work, we combine an all optical PAT system with an OCT system featuring a phase stable akinetic swept source. This multimodal PAT/OCT/OCT-angiography system provides us co-registered human skin vasculature information as well as the structural information of cutaneous. The scanning units of the sub-systems are assembled into one probe, which is then mounted onto a portable rack. The probe and rack design gives six degrees of freedom, allowing the multimodal optical imaging probe to access nearly all regions of human body. Utilizing this probe, we perform imaging on patients with various skin disorders as well as on healthy controls. Fused PAT/OCT-angiography volume shows the complete blood vessel network in human skin, which is further embedded in the morphology provided by OCT. A comparison between the results from the disordered regions and the normal regions demonstrates the clinical translational value of this multimodal optical imaging system in dermatology.

The heterocyst differentiation transcriptional regulator HetR of the filamentous cyanobacterium Anabaena forms tetramers and can be regulated by phosphorylation.

PubMed

Valladares, Ana; Flores, Enrique; Herrero, Antonia

2016-02-01

Many filamentous cyanobacteria respond to the external cue of nitrogen scarcity by the differentiation of heterocysts, cells specialized in the fixation of atmospheric nitrogen in oxic environments. Heterocysts follow a spatial pattern along the filament of two heterocysts separated by ca. 10-15 vegetative cells performing oxygenic photosynthesis. HetR is a transcriptional regulator that directs heterocyst differentiation. In the model strain Anabaena sp. PCC 7120, the HetR protein was observed in various oligomeric forms in vivo, including a tetramer that peaked with maximal hetR expression during differentiation. Tetramers were not detected in a hetR point mutant incapable of differentiation, but were conspicuous in an over-differentiating strain lacking the PatS inhibitor. In differentiated filaments the HetR tetramer was restricted to heterocysts, being undetectable in vegetative cells. HetR co-purified with RNA polymerase from Anabaena mainly as a tetramer. In vitro, purified recombinant HetR was distributed between monomers, dimers, trimers and tetramers, and it was phosphorylated when incubated with (γ-(32)P)ATP. Phosphorylation and PatS hampered the accumulation of HetR tetramers and impaired HetR binding to DNA. In summary, tetrameric HetR appears to represent a functionally relevant form of HetR, whose abundance in the Anabaena filament could be negatively regulated by phosphorylation and by PatS. © 2015 John Wiley & Sons Ltd.

Nanoparticle-enhanced spectral photoacoustic tomography: effect of oxygen saturation and tissue heterogeneity

NASA Astrophysics Data System (ADS)

Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Pfefer, T. Joshua

2016-03-01

Molecular imaging for breast cancer detection, infectious disease diagnostics and preclinical animal research may be achievable through combined use of targeted exogenous agents - such as nanoparticles - and spectral Photoacoustic Tomography (PAT). However, tissue heterogeneity can alter fluence distributions and acoustic propagation, corrupting measured PAT absorption spectra and complicating in vivo nanoparticle detection and quantitation. Highly absorptive vascular structures represent a common confounding factor, and variations in vessel hemoglobin saturation (SO2) may alter spectral content of signals from adjacent/deeper regions. To evaluate the impact of this effect on PAT nanoparticle detectability, we constructed heterogeneous phantoms with well-characterized channel-inclusion geometries and biologically relevant optical and acoustic properties. Phantoms contained an array of tubes at several depths filled with hemoglobin solutions doped with varying concentrations of gold nanorods with an absorption peak at 780 nm. Both overlying and target network SO2 was tuned using sodium dithionite. Phantoms were imaged from 700 to 900 nm using a custom PAT system comprised of a tunable pulsed laser and a research-grade ultrasound system. Recovered nanoparticle spectra were analyzed and compared with results from both spectrophotometry and PAT data from waterimmersed tubes containing blood and nanoparticle solutions. Results suggested that nanoparticle selection for a given PAT application should take into account expected oxygenation states of both target blood vessel and background tissue oxygenation to achieve optimal performance.

Reliability of peripheral arterial tonometry in patients with heart failure, diabetic nephropathy and arterial hypertension.

PubMed

Weisrock, Fabian; Fritschka, Max; Beckmann, Sebastian; Litmeier, Simon; Wagner, Josephine; Tahirovic, Elvis; Radenovic, Sara; Zelenak, Christine; Hashemi, Djawid; Busjahn, Andreas; Krahn, Thomas; Pieske, Burkert; Dinh, Wilfried; Düngen, Hans-Dirk

2017-08-01

Endothelial dysfunction plays a major role in cardiovascular diseases and pulse amplitude tonometry (PAT) offers a non-invasive way to assess endothelial dysfunction. However, data about the reliability of PAT in cardiovascular patient populations are scarce. Thus, we evaluated the test-retest reliability of PAT using the natural logarithmic transformed reactive hyperaemia index (LnRHI). Our cohort consisted of 91 patients (mean age: 65±9.7 years, 32% female), who were divided into four groups: those with heart failure with preserved ejection fraction (HFpEF) ( n=25), heart failure with reduced ejection fraction (HFrEF) ( n=22), diabetic nephropathy ( n=21), and arterial hypertension ( n=23). All subjects underwent two separate PAT measurements at a median interval of 7 days (range 4-14 days). LnRHI derived by PAT showed good reliability in subjects with diabetic nephropathy (intra-class correlation (ICC) = 0.863) and satisfactory reliability in patients with both HFpEF (ICC = 0.557) and HFrEF (ICC = 0.576). However, in subjects with arterial hypertension, reliability was poor (ICC = 0.125). We demonstrated that PAT is a reliable technique to assess endothelial dysfunction in adults with diabetic nephropathy, HFpEF or HFrEF. However, in subjects with arterial hypertension, we did not find sufficient reliability, which can possibly be attributed to variations in heart rate and the respective time of the assessments. Clinical Trial Registration Identifier: NCT02299960.

Higher pericardial adiposity is associated with prevalent diabetes: The Coronary Artery Risk Development in Young Adults study

PubMed Central

AC, Alman; DR, Jacobs; CE, Lewis; JK, Snell-Bergeon; MR, Carnethon; JG, Terry; DC, Goff; J, Ding; JJ, Carr

2016-01-01

Background and Aims Pericardial adipose tissue (PAT) is located on both sides of the pericardium. We tested whether PAT was associated with prevalent diabetes at the year 25 exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Methods and Results The CARDIA Year 25 exam (2010-2011) included complete data for all covariates on 3107 participants. Prevalent diabetes (n=436) was defined as high fasting (≥126 mg/dl) or 2-hour postload glucose (≥200 mg/dl) or HbA1c (≥6.5%) or use of diabetes medications. Volume of PAT was measured from computed tomographic scans. Logistic regression was performed to examine the relationship between quartiles of PAT and diabetes. In regression models adjusted for field center, sex, race, age, systolic blood pressure, total cholesterol, log triglycerides, and treatment with blood pressure and cholesterol lowering medication, PAT volume in the 4th quartile was significantly associated with diabetes status after adjustment for BMI (OR 2.57, 95% CI 1.66, 3.98) or visceral adipose tissue (OR 2.08, 95% CI 1.32, 3.29). PAT volume in the 2nd and 3rd quartiles was not significantly associated with diabetes status relative to the first quartile. Conclusions Metabolically active pericardial adipose tissue is associated with prevalent diabetes only at higher volumes independent of overall obesity. PMID:26803596

Listening to light scattering in turbid media: quantitative optical scattering imaging using photoacoustic measurements with one-wavelength illumination

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Li, Xiaoqi; Xi, Lei

2014-06-01

Biomedical photoacoustic tomography (PAT), as a potential imaging modality, can visualize tissue structure and function with high spatial resolution and excellent optical contrast. It is widely recognized that the ability of quantitatively imaging optical absorption and scattering coefficients from photoacoustic measurements is essential before PAT can become a powerful imaging modality. Existing quantitative PAT (qPAT), while successful, has been focused on recovering absorption coefficient only by assuming scattering coefficient a constant. An effective method for photoacoustically recovering optical scattering coefficient is presently not available. Here we propose and experimentally validate such a method for quantitative scattering coefficient imaging using photoacoustic data from one-wavelength illumination. The reconstruction method developed combines conventional PAT with the photon diffusion equation in a novel way to realize the recovery of scattering coefficient. We demonstrate the method using various objects having scattering contrast only or both absorption and scattering contrasts embedded in turbid media. The listening-to-light-scattering method described will be able to provide high resolution scattering imaging for various biomedical applications ranging from breast to brain imaging.

Pit-a-Pat: A Smart Electrocardiogram System for Detecting Arrhythmia.

PubMed

Park, Juyoung; Lee, Kuyeon; Kang, Kyungtae

2015-10-01

Electrocardiogram (ECG) telemonitoring is one of the most promising applications of medical telemetry. However, previous approaches to ECG telemonitoring have largely relied on public databases of ECG results. In this article we propose a smart ECG system called Pit-a-Pat, which extracts features from ECG signals and detects arrhythmia. It is designed to run on an Android™ (Google, Mountain View, CA) device, without requiring modifications to other software. We implemented the Pit-a-Pat system using a commercial ECG device, and the experimental results demonstrate the effectiveness and accuracy of Pit-a-Pat for monitoring the ECG signal and analyzing the cardiac activity of a mobile patient. The proposed system allows monitoring of cardiac activity with automatic analysis, thereby providing a convenient, inexpensive, and ubiquitous adjunct to personal healthcare.

Air transport of plutonium metal: content expansion initiative for the plutonium air transportable (PAT01) packaging

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

Caviness, Michael L; Mann, Paul T; Yoshimura, Richard H

2010-01-01

The National Nuclear Security Administration (NNSA) has submitted an application to the Nuclear Regulatory Commission (NRC) for the air shipment of plutonium metal within the Plutonium Air Transportable (PAT-1) packaging. The PAT-1 packaging is currently authorized for the air transport of plutonium oxide in solid form only. The INMM presentation will provide a limited overview of the scope of the plutonium metal initiative and provide a status of the NNSA application to the NRC.

Molecular interactions of agonist and inverse agonist ligands at serotonin 5-HT2C G protein-coupled receptors: computational ligand docking and molecular dynamics studies validated by experimental mutagenesis results

NASA Astrophysics Data System (ADS)

Córdova-Sintjago, Tania C.; Liu, Yue; Booth, Raymond G.

2015-02-01

To understand molecular determinants for ligand activation of the serotonin 5-HT2C G protein-coupled receptor (GPCR), a drug target for obesity and neuropsychiatric disorders, a 5-HT2C homology model was built according to an adrenergic β2 GPCR (β2AR) structure and validated using a 5-HT2B GPCR crystal structure. The models were equilibrated in a simulated phosphatidyl choline membrane for ligand docking and molecular dynamics studies. Ligands included (2S, 4R)-(-)-trans-4-(3'-bromo- and trifluoro-phenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalene-2-amine (3'-Br-PAT and 3'-CF3-PAT), a 5-HT2C agonist and inverse agonist, respectively. Distinct interactions of 3'-Br-PAT and 3'-CF3-PAT at the wild-type (WT) 5-HT2C receptor model were observed and experimental 5-HT2C receptor mutagenesis studies were undertaken to validate the modelling results. For example, the inverse agonist 3'-CF3-PAT docked deeper in the WT 5-HT2C binding pocket and altered the orientation of transmembrane helices (TM) 6 in comparison to the agonist 3'-Br-PAT, suggesting that changes in TM orientation that result from ligand binding impact function. For both PATs, mutation of 5-HT2C residues S3.36, T3.37, and F5.47 to alanine resulted in significantly decreased affinity, as predicted from modelling results. It was concluded that upon PAT binding, 5-HT2C residues T3.37 and F5.47 in TMs 3 and 5, respectively, engage in inter-helical interactions with TMs 4 and 6, respectively. The movement of TMs 5 and 6 upon agonist and inverse agonist ligand binding observed in the 5-HT2C receptor modelling studies was similar to movements reported for the activation and deactivation of the β2AR, suggesting common mechanisms among aminergic neurotransmitter GPCRs.

Raman spectroscopy as a PAT for pharmaceutical blending: Advantages and disadvantages.

PubMed

Riolo, Daniela; Piazza, Alessandro; Cottini, Ciro; Serafini, Margherita; Lutero, Emilio; Cuoghi, Erika; Gasparini, Lorena; Botturi, Debora; Marino, Iari Gabriel; Aliatis, Irene; Bersani, Danilo; Lottici, Pier Paolo

2018-02-05

Raman spectroscopy has been positively evaluated as a tool for the in-line and real-time monitoring of powder blending processes and it has been proved to be effective in the determination of the endpoint of the mixing, showing its potential role as process analytical technology (PAT). The aim of this study is to show advantages and disadvantages of Raman spectroscopy with respect to the most traditional HPLC analysis. The spectroscopic results, obtained directly on raw powders, sampled from a two-axis blender in real case conditions, were compared with the chromatographic data obtained on the same samples. The formulation blend used for the experiment consists of active pharmaceutical ingredient (API, concentrations 6.0% and 0.5%), lactose and magnesium stearate (as excipients). The first step of the monitoring process was selecting the appropriate wavenumber region where the Raman signal of API is maximal and interference from the spectral features of excipients is minimal. Blend profiles were created by plotting the area ratios of the Raman peak of API (A API ) at 1598cm -1 and the Raman bands of excipients (A EXC ), in the spectral range between 1560 and 1630cm -1 , as a function of mixing time: the API content can be considered homogeneous when the time-dependent dispersion of the area ratio is minimized. In order to achieve a representative sampling with Raman spectroscopy, each sample was mapped in a motorized XY stage by a defocused laser beam of a micro-Raman apparatus. Good correlation between the two techniques has been found only for the composition at 6.0% (w/w). However, standard deviation analysis, applied to both HPLC and Raman data, showed that Raman results are more substantial than HPLC ones, since Raman spectroscopy enables generating data rich blend profiles. In addition, the relative standard deviation calculated from a single map (30 points) turned out to be representative of the degree of homogeneity for that blend time. Copyright © 2017 Elsevier B.V. All rights reserved.

Monitoring ibuprofen-nicotinamide cocrystal formation during solvent free continuous cocrystallization (SFCC) using near infrared spectroscopy as a PAT tool.

PubMed

Kelly, A L; Gough, T; Dhumal, R S; Halsey, S A; Paradkar, A

2012-04-15

The purpose of this work was to explore NIR spectroscopy as a PAT tool to monitor the formation of ibuprofen and nicotinamide cocrystals during extrusion based solvent free continuous cocrystallization (SFCC). Drug and co-former were gravimetrically fed into a heated co-rotating twin screw extruder to form cocrystals. Real-time process monitoring was performed using a high temperature NIR probe in the extruder die to assess cocrystal content and subsequently compared to off-line powder X-ray diffraction measurements. The effect of processing variables, such as temperature and mixing intensity, on the extent of cocrystal formation was investigated. NIR spectroscopy was sensitive to cocrystal formation with the appearance of new peaks and peak shifts, particularly in the 4800-5200 cm(-1) wave-number region. PXRD confirmed an increased conversion of the mixture into cocrystal with increase in barrel temperature and screw mixing intensity. A decrease in screw rotation speed also provided improved cocrystal yield due to the material experiencing longer residence times within the process. A partial least squares analysis in this region of NIR spectrum correlated well with PXRD data, providing a best fit with cocrystal conversion when a limited range of process conditions were considered, for example a single set temperature. The study suggests that NIR spectroscopy could be used to monitor cocrystal purity on an industrial scale using this continuous, solvent-free process. Copyright © 2011 Elsevier B.V. All rights reserved.

View-Based Models of 3D Object Recognition and Class-Specific Invariance

DTIC Science & Technology

1994-04-01

underlie recognition of geon-like com- ponents (see Edelman, 1991 and Biederman , 1987 ). I(X -_ ta)II1y = (X - ta)TWTW(x -_ ta) (3) View-invariant features...Institute of Technology, 1993. neocortex. Biological Cybernetics, 1992. 14] I. Biederman . Recognition by components: a theory [20] B. Olshausen, C...Anderson, and D. Van Essen. A of human image understanding. Psychol. Review, neural model of visual attention and invariant pat- 94:115-147, 1987 . tern

Characterization of a nonribosomal peptide antibiotic solid dispersion formulation by process analytical technologies sensors.

PubMed

Rahman, Ziyaur; Siddiqui, Akhtar; Khan, Mansoor A

2013-12-01

The focus of present investigation was to characterize and evaluate the variability of solid dispersion (SD) of amorphous vancomycin (VCM), utilizing crystalline polyethylene glycol (PEG-6000) as a carrier and subsequently, determining their percentage composition by nondestructive method of process analytical technology (PAT) sensors. The SD were prepared by heat fusion method and characterized for physicochemical and spectral properties. Enhanced dissolution was shown by the SD formulations. Decreased crystallinity of PEG-6000 was observed indicating that the drug was present as solution and dispersed form within the polymer. The SD formulations were homogenous as shown by near infrared (NIR) chemical imaging data. Principal component analysis (PCA) and partial least square (PLS) method were applied to NIR and PXRD (powder X-ray diffraction) data to develop model for quantification of drug and carrier. PLS of both data showed correlation coefficient >0.9934 with good prediction capability as revealed by smaller value of root mean square and standard error. The model based on NIR and PXRD were two folds more accurate in estimating PEG-6000 than VCM. In conclusion, the drug dissolution from the SD increased by decreasing crystallinity of PEG-6000, and the chemometric models showed usefulness of PAT sensor in estimating percentage of both VCM and PEG-600 simultaneously. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Comparison of methods for determination of volatile organic compounds in drinking water.

PubMed

Golfinopoulos, S K; Lekkas, T D; Nikolaou, A D

2001-10-01

Comparison of four methods including liquid-liquid extraction (LLE), direct aqueous injection (DAI), purge and trap (PAT) and head space (HS) were carried out in this work for determination of volatile organic compounds (VOCs) including trihalomethanes (THMs) in drinking water. This comparison is made especially to show the advantages and disadvantages and specifically the different detection limits (DL) that can be obtained for a given type of analysis. LLE is applicable only for determination of the THMs concentrations, while DAI, PAT, HS methods with different DL each of them are applicable for all VOCs, with PAT to be the most sensitive. Sampling apparatus and procedure for all these methods except of PAT are very simple and easy, but possible disadvantages for LLE and DAI are the low sensitivity and especially the detection only of THMs with LLE.

Anger, depression and anxiety associated with endothelial function in childhood and adolescence.

PubMed

Osika, W; Montgomery, S M; Dangardt, F; Währborg, P; Gan, L M; Tideman, E; Friberg, P

2011-01-01

Psychosocial adversity is a risk factor for cardiovascular disease (CVD) in adults. The authors assessed associations of reactive hyperaemia peripheral arterial tonometry (RH-PAT), a measure of endothelial function predictive of CVD, with self-assessed psychological health among school children. A total of 248 healthy school children (mean (SD) age 14.0 (1.0); 136 girls and 112 boys) underwent RH-PAT testing. They completed the Beck Youth Inventories (BYI) of emotional and social impairment scales, which is used to screen for depression, anxiety, anger and disruptive behaviour. No sex differences were observed for the RH-PAT score. Statistically significant differences were observed for the BYI scores; girls had higher scores for depression, anger and anxiety. Among the girls, there were statistically significant associations between lower RH-PAT scores and higher scores for anger (B coefficient=-0.100, p=0.040), depression (-0.108, p=0.009) and anxiety (-0.138, p=0.039) after adjustment for age. Among the boys, disruptive behaviour was associated with higher RH-PAT scores (0.09, p=0.006). The girls have higher levels of self-assessed anger; depression and anxiety compared with the boys, and these characteristics are associated with lower RH-PAT scores, indicating attenuated endothelial function. Among the boys, disruptive behaviour was associated with better endothelial function. Although psychological ill-health is associated with impaired endothelial function and CVD among adults, such processes may also be relevant to children. Psychosocial adversity in childhood might be a risk factor for subsequent CVD.

Tannic Acid/Fe3+/Ag Nanofilm Exhibiting Superior Photodynamic and Physical Antibacterial Activity.

PubMed

Xu, Ziqiang; Wang, Xiuhua; Liu, Xiangmei; Cui, Zhenduo; Yang, Xianjin; Yeung, Kelvin Wai Kwok; Chung, Jonathan Chiyuen; Chu, Paul K; Wu, Shuilin

2017-11-15

Silver nanoparticles (AgNPs) enwrapped in the biologically safe tannic acid (TA)/Fe 3+ nanofilm are synthesized by an ultrafast, green, simple, and universal method. The physical antibacterial activity and photodynamic antibacterial therapy (PAT) efficacy of the TA/Fe 3+ /AgNPs nanofilm were investigated for the first time, which exhibited a strong physical antibacterial activity as well as great biocompatibility, through in vitro and in vivo studies. The results disclosed that this hybrid coating could possess high PAT capabilities upon irradiation under a visible light of 660 nm, which is longer than those of previously reported green and blue sensitization light, thus allowing deeper light penetration into biological tissues. Electron spin resonance (ESR) spectra proved that the PAT efficacy of the TA/Fe 3+ /AgNPs nanofilm was associated with the yields of singlet oxygen ( 1 O 2 ) under the irradiation of visible light (660 nm). A higher PAT efficiency of 100 and 94% against Escherichia coli and Staphylococcus aureus could be achieved within 20 min of illumination under 660 nm visible light, whereas the innate physical antibacterial activity of AgNPs could endow the implants with long-term prevention of bacterial infection. The mechanism of PAT may be associated with the formation of oxidative stress and oxidative damage to key biomolecules (proteins and lipids) in bacteria. Our results reveal that the synergistic action of both PAT and physical action of AgNPs in this hybrid nanofilm is an effective way to inactivate bacteria, with minimal side effects.

Emerging Roles of DHHC-mediated Protein S-palmitoylation in Physiological and Pathophysiological Context.

PubMed

De, Indranil; Sadhukhan, Sushabhan

2018-03-22

Protein S-palmitoylation refers to a post-translational modification (PTM) wherein palmitic acid, a 16-carbon long saturated fatty acid gets covalently attached to Cys sidechain of a protein. It has been known to the literature for almost 50 years and in general, this PTM is believed to facilitate membrane attachments of proteins for the obvious hydrophobicity of the palmitoyl group. But after the discovery of the protein palmitoyl acyltransferases (PATs, also known as DHHC-PATs), a major paradigm shift has been observed in the field of protein S-palmitoylation. A family of 23 mammalian DHHC-PATs has been identified and the majority of them are associated with many human diseases spanning from neuropsychiatric diseases to cancers. Novel unique and essential role of DHHC-mediated protein S-palmitoylation has been revealed apart from its membrane trafficking role. Biomedical importance of DHHCs has also been reiterated with small molecule inhibitors for DHHCs as well as in DHHC-knockout mice or mouse Xenograft models. In this review, we present recent advances in the field of protein S-palmitoylation and the involvement of individual DHHC isoforms in human diseases. In addition, the recent development of the analytical tools to study S-palmitoylation and their inhibitors are discussed in detail. We also highlight the issues that need to be addressed in detail to further develop our understanding on protein S-palmitoylation and strongly believe that pharmacological modulation of DHHC-mediated protein S-palmitoylation has a massive potential to emerge as a novel therapeutic strategy for human diseases. It will not be surprising if reversible protein S-palmitoylation prove to be an indispensable PTM that regulates a host of cellular processes, just like protein phosphorylation or ubiquitination. Copyright © 2018 Elsevier GmbH. All rights reserved.

Unilateral purpura annularis telangiectodes of majocchi in an elderly male: an atypical presentation.

PubMed

Wang, Apphia; Shuja, Fareesa; Chan, Audrey; Wasko, Carina

2013-08-15

Purpura annularis telangiectodes (PAT), also known as Majocchi purpura, is a rare form of pigmented purpuric dermatosis characterized by non-palpable red-brown, occasionally pruritic patches which progress to hyperpigmented halos. Purpura annularis telangiectodes usually presents in female adolescents as benign symmetric lesions with a predilection for the lower extremities. We present an atypical case of unilateral PAT in an elderly male. To our knowledge, our patient at 85-years-old is the oldest PAT and first unilateral purpura annularis telangiectodes case described in the literature.

PatGen--a consolidated resource for searching genetic patent sequences.

PubMed

Rouse, Richard J D; Castagnetto, Jesus; Niedner, Roland H

2005-04-15

Compared to the wealth of online resources covering genomic, proteomic and derived data the Bioinformatics community is rather underserved when it comes to patent information related to biological sequences. The current online resources are either incomplete or rather expensive. This paper describes, PatGen, an integrated database containing data from bioinformatic and patent resources. This effort addresses the inconsistency of publicly available genetic patent data coverage by providing access to a consolidated dataset. PatGen can be searched at http://www.patgendb.com rjdrouse@patentinformatics.com.

Pericardial adipose tissue and the metabolic syndrome is increased in patients with chronic major depressive disorder compared to acute depression and controls.

PubMed

Kahl, K G; Herrmann, J; Stubbs, B; Krüger, T H C; Cordes, J; Deuschle, M; Schweiger, U; Hüper, K; Helm, S; Birkenstock, A; Hartung, D

2017-01-04

Major depressive disorder (MDD) is associated with an estimated fourfold risk for premature death, largely attributed to cardiovascular disorders. Pericardial adipose tissue (PAT), a fat compartment surrounding the heart, has been implicated in the development of coronary artery disease. An unanswered question is whether people with chronic MDD are more likely to have elevated PAT volumes versus acute MDD and controls (CTRL). The study group consists of sixteen patients with chronic MDD, thirty-four patients with acute MDD, and twenty-five CTRL. PAT and adrenal gland volume were measured by magnetic resonance tomography. Additional measures comprised factors of the metabolic syndrome, cortisol, relative insulin resistance, and pro-inflammatory cytokines (interleukin-6; IL-6 and tumor necrosis factor-α, TNF-α). PAT volumes were significantly increased in patients with chronic MDD>patients with acute MDD>CTRL. Adrenal gland volume was slightly enlarged in patients with chronic MDD>acute MDD>CTRL, although this difference failed to reach significance. The PAT volume was correlated with adrenal gland volume, and cortisol concentrations were correlated with depression severity, measured by BDI-2 and MADRS. Group differences were found concerning the rate of the metabolic syndrome, being most frequent in chronic MDD>acute MDD>CTRL. Further findings comprised increased fasting cortisol, increased TNF-α concentration, and decreased physical activity level in MDD compared to CTRL. Our results extend the existing literature in demonstrating that patients with chronic MDD have the highest risk for developing cardiovascular disorders, indicated by the highest PAT volume and prevalence of metabolic syndrome. The correlation of PAT with adrenal gland volume underscores the role of the hypothalamus-pituitary-adrenal system as mediator for body-composition changes. Metabolic monitoring, health advices and motivation for the improvement of physical fitness may be recommended in depressed patients, in particular in chronic depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of Posterior Approach With Intramedullary Nailing Versus Lateral Transfibular Approach With Fixed-Angle Plating for Tibiotalocalcaneal Arthrodesis.

PubMed

Mulligan, Ryan P; Adams, Samuel B; Easley, Mark E; DeOrio, James K; Nunley, James A

2017-12-01

A variety of operative approaches and fixation techniques have been described for tibiotalocalcaneal (TTC) arthrodesis. The intramedullary (IM) nail and lateral, fixed-angle plating are commonly used because of ease of use and favorable biomechanical properties. A lateral, transfibular (LTF) approach allows for direct access to the tibiotalar and subtalar joints, but the posterior, Achilles tendon-splitting (PATS) approach offers a robust soft tissue envelope. The purpose of this study was to compare the results of TTC arthrodesis with either a PATS approach with IM nailing or LTF approach with fixed-angle plating. A retrospective review was performed on all patients who underwent simultaneous TTC arthrodesis with minimum 1 year clinical and radiographic follow up. Patients were excluded if they underwent TTC arthrodesis through an approach other than PATS or LTF, and received fixation without an IM nail or fixed-angle plate. Primary outcomes examined were union rate, revisions, and complications. Thirty-eight patients underwent TTC arthrodesis with a PATS approach and IM nailing, and 28 with a LTF approach and lateral plating. The overall union rate was 71%; 76% (29 of 38 patients) for the PATS/IM nail group, and 64% (18 of 28) for LTF/plating group ( P = .41). Symptomatic nonunion requiring revision arthrodesis occurred in 16% (6 of 38) of the PATS/IM nail group versus 7% (2 of 28) in the LTF/lateral plating group ( P = .45). There were no significant differences in individual tibiotalar or subtalar union rates, superficial wound problems, infection, symptomatic hardware, stress fractures, or nerve irritations. Union, revision, and complication rates were similar for TTC arthrodesis performed with a PATS approach and IM nail compared with an LTF approach and fixed-angle plate in a complex patient population. Both techniques were adequate, especially when prior incisions, preexisting hardware, or deformity preclude options. Level III, retrospective comparative study.

Analysis of substrate specificity of human DHHC protein acyltransferases using a yeast expression system

PubMed Central

Ohno, Yusuke; Kashio, Atsushi; Ogata, Ren; Ishitomi, Akihiro; Yamazaki, Yuki; Kihara, Akio

2012-01-01

Palmitoylation plays important roles in the regulation of protein localization, stability, and activity. The protein acyltransferases (PATs) have a common DHHC Cys-rich domain. Twenty-three DHHC proteins have been identified in humans. However, it is unclear whether all of these DHHC proteins function as PATs. In addition, their substrate specificities remain largely unknown. Here we develop a useful method to examine substrate specificities of PATs using a yeast expression system with six distinct model substrates. We identify 17 human DHHC proteins as PATs. Moreover, we classify 11 human and 5 yeast DHHC proteins into three classes (I, II, and III), based on the cellular localization of their respective substrates (class I, soluble proteins; class II, integral membrane proteins; class III, lipidated proteins). Our results may provide an important clue for understanding the function of individual DHHC proteins. PMID:23034182

The Collins Center Update. Volume 1, Issue 3, December 1999

DTIC Science & Technology

1999-12-01

CDN), devel oped and executed the FORO DE ESTRATEGIA NACIONAL 2005 Hon­ du ras en el Siglo XXI (FEN 2005) {Na tional Strategy Forum 2005 Hon du­ ras...tools and processes used to make strate gic leaders. Im­ pressed with this program, Gover nor Pat ton requested a return visit with his en tire...wide command post and field train ing exer cise which tests and vali­ dates nuclear command and control, and exe cu tion proce dures. It is based on a

Discover Supercomputer 5

NASA Image and Video Library

2017-12-08

Two rows of the “Discover” supercomputer at the NASA Center for Climate Simulation (NCCS) contain more than 4,000 computer processors. Discover has a total of nearly 15,000 processors. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

Discover Supercomputer 4

NASA Image and Video Library

2017-12-08

This close-up view highlights one row—approximately 2,000 computer processors—of the “Discover” supercomputer at the NASA Center for Climate Simulation (NCCS). Discover has a total of nearly 15,000 processors. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

2006 Chemical Biological Individual Protection (CBIP) Conference and Exhibition

DTIC Science & Technology

2006-03-09

306 405 107 108 207 208 307 308 407 109 310 409 111 312 411 406 408 412 410 113 112 20 20 Lounge 20 20 314 413 414 404 402 Exhibit hall Company Name...Sigmon Group 312 Nor E First Response, Inc 314 Milliken & Company 401 TSI Incorporated 402 CDO Technologies, Inc. 403 Ahura Corp. 404...410 E -Z-EM, Inc. 411 Safety Equipment America Inc 412 Remploy Ltd. 414 NotEs NotEs NotEs Mask Fitting - M41 PATS Protective Assessment Test

Detection of Parent-of-Origin Effects Using General Pedigree Data

PubMed Central

Zhou, Ji-Yuan; Ding, Jie; Fung, Wing K.; Lin, Shili

2010-01-01

Genomic imprinting is an important epigenetic factor in complex traits study, which has generally been examined by testing for parent-of-origin effects of alleles. For a diallelic marker locus, the parental-asymmetry test (PAT) based on case-parents trios and its extensions to incomplete nuclear families (1-PAT and C-PAT) are simple and powerful for detecting parent-of-origin effects. However, these methods are suitable only for nuclear families and thus are not amenable to general pedigree data. Use of data from extended pedigrees, if available, may lead to more powerful methods than randomly selecting one two-generation nuclear family from each pedigree. In this study, we extend PAT to accommodate general pedigree data by proposing the pedigree PAT (PPAT) statistic, which uses all informative family trios from pedigrees. To fully utilize pedigrees with some missing genotypes, we further develop the Monte Carlo (MC) PPAT (MCPPAT) statistic based on MC sampling and estimation. Extensive simulations were carried out to evaluate the performance of the proposed methods. Under the assumption that the pedigrees and their associated affection patterns are randomly drawn from a population of pedigrees with at least one affected offspring, we demonstrated that MCPPAT is a valid test for parent-of-origin effects in the presence of association. Further, MCPPAT is much more powerful compared to PAT for trios or even PPAT for all informative family trios from the same pedigrees if there is missing data. Application of the proposed methods to a rheumatoid arthritis dataset further demonstrates the advantage of MCPPAT. PMID:19676055

Relation between digital peripheral arterial tonometry and brachial artery ultrasound measures of vascular function in patients with coronary artery disease and in healthy volunteers.

PubMed

Lee, Craig R; Bass, Almasa; Ellis, Kyle; Tran, Bryant; Steele, Savanna; Caughey, Melissa; Stouffer, George A; Hinderliter, Alan L

2012-03-01

Digital peripheral arterial tonometry (PAT) is an emerging, noninvasive method to assess vascular function. The physiology underlying this phenotype, however, remains unclear. Therefore, we evaluated the relation between digital PAT and established brachial artery ultrasound measures of vascular function under basal conditions and after reactive hyperemia. Using a cross-sectional study design, digital PAT and brachial artery ultrasonography with pulsed wave Doppler were simultaneously completed at baseline and after reactive hyperemia in both those with established coronary artery disease (n = 99) and healthy volunteers with low cardiovascular disease risk (n = 40). Under basal conditions, the digital pulse volume amplitude demonstrated a significant positive correlation with the brachial artery velocity-time integral that was independent of the arterial diameter, in both the healthy volunteer (r(s) = 0.64, p <0.001) and coronary artery disease (r(s) = 0.63, p <0.001) cohorts. Similar positive relations were observed with the baseline brachial artery blood flow velocity and blood flow. In contrast, no relation between the reactive hyperemia-evoked digital PAT ratio and either brachial artery flow-mediated dilation or shear stress was observed in either cohort (p = NS). In conclusion, these findings demonstrate that the digital PAT measures of vascular function more closely reflect basal blood flow in the brachial artery than reactive hyperemia-induced changes in the arterial diameter or flow velocity, and the presence of vascular disease does not modify the physiology underlying the digital PAT phenotype. Copyright © 2012 Elsevier Inc. All rights reserved.

Persistence of culturable Escherichia coli fecal contaminants in dairy alpine grassland soils.

PubMed

Texier, Stéphanie; Prigent-Combaret, Claire; Gourdon, Marie Hélène; Poirier, Marie Andrée; Faivre, Pierre; Dorioz, Jean Marcel; Poulenard, Jérome; Jocteur-Monrozier, Lucile; Moënne-Loccoz, Yvan; Trevisan, Dominique

2008-01-01

Our knowledge of Escherichia coli (E. coli) ecology in the field is very limited in the case of dairy alpine grassland soils. Here, our objective was to monitor field survival of E. coli in cow pats and underlying soils in four different alpine pasture units, and to determine whether the soil could constitute an environmental reservoir. E. coli was enumerated by MPN using a selective medium. E. coli survived well in cow pats (10(7) to 10(8) cells g(-1) dry pat), but cow pats disappeared within about 2 mo. In each pasture unit, constant levels of E. coli (10(3) to 10(4) cells g(-1) dry soil) were recovered from all topsoil (0-5 cm) samples regardless of the sampling date, that is, under the snow cover, immediately after snow melting, or during the pasture season (during and after the decomposition of pats). In deeper soil layers below the root zone (5-25 cm), E. coli persistence varied according to soil type, with higher numbers recovered in poorly-drained soils (10(3) to 10(4) cells g(-1) dry soil) than in well-drained soils (< 10(2) cells g(-1) dry soil). A preliminary analysis of 38 partial uidA sequences of E. coli from pat and soils highlighted a cluster containing sequences only found in this work. Overall, this study raises the possibility that fecal E. coli could have formed a naturalized (sub)population, which is now part of the indigenous soil community of alpine pasture grasslands, the soil thus representing an environmental reservoir of E. coli.

Solid state laser communications in space (SOLACOS) position, acquisition, and tracking (PAT) subsystem implementation

NASA Astrophysics Data System (ADS)

Flemmig, Joerg; Pribil, Klaus

1994-09-01

This paper presents the concept and implementation aspects of the Pointing, Acquisition and Tracking Subsystem (PAT) which is developed in the frame of the SOLACOS (Solid State Laser Communications in Space) program.

Use of Percutaneous Aspiration Thrombectomy vs. Anticoagulation Therapy to Treat Acute Iliofemoral Venous Thrombosis: 1-year Follow-up Results of a Randomised, Clinical Trial

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

Cakir, Volkan, E-mail: drvolkancakir@gmail.com; Gulcu, Aytac, E-mail: aytac.gulcu@deu.edu.tr; Akay, Emrah, E-mail: emrahakay@hotmail.com

2014-08-15

PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (nmore » 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical symptoms. PAT is a safe, inexpensive, and easily performed method of endovascular treatment with a low rate of major complications. Our present findings and literature data suggest that PAT can be used as first-line treatment in proximal deep vein thrombosis patients, especially when thrombolytic treatment is contraindicated.« less

Non-contact photoacoustic tomography and ultrasonography for brain imaging

NASA Astrophysics Data System (ADS)

Rousseau, Guy; Blouin, Alain; Monchalin, Jean-Pierre

2012-02-01

Photoacoustic tomography (PAT) and ultrasonography (US) of biological tissues usually rely on transducer arrays for the detection of ultrasound. Obtaining the best sensitivity requires a physical contact with the tissue using an intermediate coupling fluid (water or gel). This type of contact is a major drawback for several applications such as neurosurgery. Laser-ultrasonics is an established optical technique for the non-contact generation and detection of ultrasound in industrial materials. In this paper, the non-contact detection scheme used in laser-ultrasonics is adapted to allow probing of ultrasound in biological tissues while remaining below laser exposure safety limits. Both non-contact PAT (NCPAT) and non-contact US (NCUS) are demonstrated experimentally using a single-frequency detection laser emitting suitably shaped pulses and a confocal Fabry-Perot interferometer. It is shown that an acceptable sensitivity is obtained while remaining below the maximum permissible exposure (MPE) of biological tissues. Results obtained ex vivo with a calf brain specimen show that sub-mm endogenous and exogenous inclusions can be detected at depths exceeding 1 cm. When fully developed, the technique could be a unique diagnostic tool in neurosurgery providing deep imaging of blood vessels, blood clots and blood oxygenation.

New Frontiers AO: Advanced Materials Bi-propellant Rocket (AMBR) Engine Information Summary

NASA Technical Reports Server (NTRS)

Liou, Larry C.

2008-01-01

The Advanced Material Bi-propellant Rocket (AMBR) engine is a high performance (I(sub sp)), higher thrust, radiation cooled, storable bi-propellant space engine of the same physical envelope as the High Performance Apogee Thruster (HiPAT(TradeMark)). To provide further information about the AMBR engine, this document provides details on performance, development, mission implementation, key spacecraft integration considerations, project participants and approach, contact information, system specifications, and a list of references. The In-Space Propulsion Technology (ISPT) project team at NASA Glenn Research Center (GRC) leads the technology development of the AMBR engine. Their NASA partners were Marshall Space Flight Center (MSFC) and Jet Propulsion Laboratory (JPL). Aerojet leads the industrial partners selected competitively for the technology development via the NASA Research Announcement (NRA) process.

75 FR 25855 - Clean Air Act Advisory Committee (CAAAC): Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

... contact Pat Childers, Office of Air and Radiation, U.S. EPA (202) 564-1082, FAX (202) 564-1352 or by mail... disabilities, please contact Mr. Pat Childers at (202) 564-1082 or [email protected] . To request...

75 FR 1379 - Clean Air Act Advisory Committee (CAAAC): Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

...: Concerning the CAAAC, please contact Pat Childers, Office of Air and Radiation, U.S. EPA (202) 564-1082, FAX... individuals with disabilities, please contact Mr. Pat Childers at (202) 564-1082 or [email protected] . To...

77 FR 52328 - Clean Air Act Advisory Committee (CAAAC): Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-29

..., please contact Pat Childers, Office of Air and Radiation, U.S. EPA (202) 564-1082, Fax (202) 564-1352 or... services for individuals with disabilities, please contact Mr. Pat Childers at (202) 564-1082 or childers...

75 FR 79369 - Clean Air Act Advisory Committee (CAAAC): Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

..., please contact Pat Childers, Office of Air and Radiation, U.S. EPA (202) 564-1082, FAX (202) 564-1352 or... contact Mr. Pat Childers at (202) 564-1082 or [email protected] . To request accommodation of a...

77 FR 20395 - Clean Air Act Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-04

... Pat Childers, Office of Air and Radiation, U.S. EPA (202) 564-1082, Fax (202) 564-1352 or by mail at U... services for individuals with disabilities, please contact Mr. Pat Childers at (202) 564-1082 or childers...

75 FR 56530 - Clean Air Act Advisory Committee (CAAAC): Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

...: Concerning the CAAAC, please contact Pat Childers, Office of Air and Radiation, U.S. EPA, (202) 564-1082, FAX... individuals with disabilities, please contact Mr. Pat Childers at (202) 564-1082 or [email protected] . To...

[Catalytic properties of enzymes from Erwinia carotovora involved in transamination of phenylpyruvate].

PubMed

Paloian, A M; Stepanian, L A; Dadaian, S A; Ambartsumian, A A; Alebian, G P; Sagian, A S

2013-01-01

Km for L-phenylalanine, L-glutamic acid, L-aspartic acid, and the corresponding keto acids were calculated, as well as Vmax, was measured for the following pairs of substrates: L-phenylalanine-2-ketoglutarate, L-phenylalanine-oxaloacetate, L-glutamic acid-phenylpyruvate, and L-aspartic acid-phenylpyruvate for aminotransferases PATI, PAT2, and PAT3 from Erwinia carotovora catalyzing transamination of phenylpyruvate. The ping-pong bi-bi mechanism was shown for the studied aminotransferases. The substrate inhibition (Ks) of PAT3 with 2-ketoglutarate and oxaloacetate was 10.23 +/- 3.20 and 3.73 +/- 1.99 mM, respectively.

The role of adipose-derived inflammatory cytokines in type 1 diabetes

PubMed Central

Shao, Lan; Feng, Boya; Zhang, Yuying; Zhou, Huanjiao; Ji, Weidong; Min, Wang

2016-01-01

ABSTRACT Adipose tissue dysfunction correlates with the development of diabetes. Mice with an adipocyte-specific deletion of the SUMO-specific protease SENP1 develop symptoms of type-1 diabetes mellitus (T1DM). Peri-pancreatic adipocytes (PATs) exert both systemic and paracrine effects on pancreases function. Our recent studies report that PATs of SENP1-deficient mice have increased proinflammatory cytokine production compared with other adipose depots. Proinflammatory cytokines produced from PATs not only have direct cytotoxic effects on pancreatic islets, but also increase CCL5 expression in adjacent pancreatic islets, which induces persistent inflammation in pancreases by acquisition of Th1 and Th17 effector T cell subsets. Small ubiquitin-like modifier (SUMO) can post-translationally conjugate to cellular proteins (SUMOylation) and modulate their biological functions. Several components in SUMOylation associate with T1DM susceptibility. We find that SUMOylation of NF-κB essential molecule NEMO augments NF-κB activity, NF-κB-dependent cytokine production and pancreatic inflammation. NF-κB inhibitor should provide therapeutic approach to block PAT inflammation and ameliorate the T1DM phenotype. We further propose that adipocytes in PATs may play a primary role in establishing pancreatic immune regulation at onset of diabetes, providing new insights into the molecular pathogenesis of type 1 diabetes. PMID:27617172

Real-time photoacoustic and ultrasound dual-modality imaging system facilitated with graphics processing unit and code parallel optimization.

PubMed

Yuan, Jie; Xu, Guan; Yu, Yao; Zhou, Yu; Carson, Paul L; Wang, Xueding; Liu, Xiaojun

2013-08-01

Photoacoustic tomography (PAT) offers structural and functional imaging of living biological tissue with highly sensitive optical absorption contrast and excellent spatial resolution comparable to medical ultrasound (US) imaging. We report the development of a fully integrated PAT and US dual-modality imaging system, which performs signal scanning, image reconstruction, and display for both photoacoustic (PA) and US imaging all in a truly real-time manner. The back-projection (BP) algorithm for PA image reconstruction is optimized to reduce the computational cost and facilitate parallel computation on a state of the art graphics processing unit (GPU) card. For the first time, PAT and US imaging of the same object can be conducted simultaneously and continuously, at a real-time frame rate, presently limited by the laser repetition rate of 10 Hz. Noninvasive PAT and US imaging of human peripheral joints in vivo were achieved, demonstrating the satisfactory image quality realized with this system. Another experiment, simultaneous PAT and US imaging of contrast agent flowing through an artificial vessel, was conducted to verify the performance of this system for imaging fast biological events. The GPU-based image reconstruction software code for this dual-modality system is open source and available for download from http://sourceforge.net/projects/patrealtime.

[Prism adaptation test before strabismus surgery : Results of a survey and literature review].

PubMed

Pichler, U; Rohleder, M; Ehrt, O

2018-02-01

Variable preoperative deviations and compensatory mechanisms may cause wrong dosage of strabismus surgery and result in over- or undercorrection. A long-lasting prism adaptation test (PAT) before surgery is supposed to reduce those difficulties and to improve the postoperative results. To date, the use of prism adaptation before surgery has not been systematically examined. A total of 15 strabismologists and 28 orthoptists in Austria were interviewed about their approach to prism adaptation in 9 types of strabismus. They were also asked about the basis of their decision for a certain treatment regime. Of those interviewed, 28% performed preoperative prism adaptation for weeks to years. Of those, 7% based their decision on evidence from the literature, 54% decide on personal experience, 15% due to guidelines of their institution, and 23% follow the teaching of their medical school. Reports in the literature reveal inconsistent results on PAT. In published studies, PAT was rarely performed longer than 4 weeks and only shows significant improvements on outcome in particular pathologies as acquired esotropia. Long-term PAT appears questionable as to date there is no evidence for a better postoperative outcome. Before setting up guidelines, further controlled, prospective studies on PAT must be conducted.

Coregistered photoacoustic and ultrasound imaging and classification of ovarian cancer: ex vivo and in vivo studies

NASA Astrophysics Data System (ADS)

Salehi, Hassan S.; Li, Hai; Merkulov, Alex; Kumavor, Patrick D.; Vavadi, Hamed; Sanders, Melinda; Kueck, Angela; Brewer, Molly A.; Zhu, Quing

2016-04-01

Most ovarian cancers are diagnosed at advanced stages due to the lack of efficacious screening techniques. Photoacoustic tomography (PAT) has a potential to image tumor angiogenesis and detect early neovascular changes of the ovary. We have developed a coregistered PAT and ultrasound (US) prototype system for real-time assessment of ovarian masses. Features extracted from PAT and US angular beams, envelopes, and images were input to a logistic classifier and a support vector machine (SVM) classifier to diagnose ovaries as benign or malignant. A total of 25 excised ovaries of 15 patients were studied and the logistic and SVM classifiers achieved sensitivities of 70.4 and 87.7%, and specificities of 95.6 and 97.9%, respectively. Furthermore, the ovaries of two patients were noninvasively imaged using the PAT/US system before surgical excision. By using five significant features and the logistic classifier, 12 out of 14 images (86% sensitivity) from a malignant ovarian mass and all 17 images (100% specificity) from a benign mass were accurately classified; the SVM correctly classified 10 out of 14 malignant images (71% sensitivity) and all 17 benign images (100% specificity). These initial results demonstrate the clinical potential of the PAT/US technique for ovarian cancer diagnosis.

Ah, That New Car Smell: NASA Technology Protects Spacecraft from Outgassed Molecular Contaminants

NASA Image and Video Library

2017-12-08

Goddard technologist Nithin Abraham, a member of the team that has developed a low-cost, low-mass technique for protecting sensitive spacecraft components from outgassed contaminants, studies a paint sample in her laboratory. To read this story go to: www.nasa.gov/topics/technology/features/outgas-tech.html Credit: NASA/Pat Izzo NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Real-time process monitoring in a semi-continuous fluid-bed dryer - microwave resonance technology versus near-infrared spectroscopy.

PubMed

Peters, Johanna; Teske, Andreas; Taute, Wolfgang; Döscher, Claas; Höft, Michael; Knöchel, Reinhard; Breitkreutz, Jörg

2018-02-15

The trend towards continuous manufacturing in the pharmaceutical industry is associated with an increasing demand for advanced control strategies. It is a mandatory requirement to obtain reliable real-time information on critical quality attributes (CQA) during every process step as the decision on diversion of material needs to be performed fast and automatically. Where possible, production equipment should provide redundant systems for in-process control (IPC) measurements to ensure continuous process monitoring even if one of the systems is not available. In this paper, two methods for real-time monitoring of granule moisture in a semi-continuous fluid-bed drying unit are compared. While near-infrared (NIR) spectroscopy has already proven to be a suitable process analytical technology (PAT) tool for moisture measurements in fluid-bed applications, microwave resonance technology (MRT) showed difficulties to monitor moistures above 8% until recently. The results indicate, that the newly developed MRT sensor operating at four resonances is capable to compete with NIR spectroscopy. While NIR spectra were preprocessed by mean centering and first derivative before application of partial least squares (PLS) regression to build predictive models (RMSEP = 0.20%), microwave moisture values of two resonances sufficed to build a statistically close multiple linear regression (MLR) model (RMSEP = 0.07%) for moisture prediction. Thereby, it could be verified that moisture monitoring by MRT sensor systems could be a valuable alternative to NIR spectroscopy or could be used as a redundant system providing great ease of application. Copyright © 2017 Elsevier B.V. All rights reserved.

Antimatter/HiPAT Support Services

NASA Technical Reports Server (NTRS)

Lewis, Raymond A.

2001-01-01

Techniques were developed for trapping normal matter in the High Performance Antiproton Trap (HiPAT). Situations encountered included discharge phenomena, charge exchange and radial diffusion processes. It is important to identify these problems, since they will also limit the performance in trapping antimatter next year.

76 FR 28026 - Clean Air Act Advisory Committee (CAAAC): Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... contact Pat Childers, Office of Air and Radiation, U.S. EPA (202) 564-1082, FAX (202) 564-1352 or by mail..., please contact Mr. Pat Childers at (202) 564-1082 or [email protected] . To request accommodation of a...

78 FR 9388 - Clean Air Act Advisory Committee (CAAAC): Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-08

... Pat Childers, Office of Air and Radiation, U.S. EPA (202) 564-1082, FAX (202) 564-1352 or by mail at U... individuals with disabilities, please contact Mr. Pat Childers at (202) 564-1082 or [email protected] . To...

78 FR 16837 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-19

... listed under ``COMMERCE/ PAT-TM-20 Customer Call Center, Assistance and Satisfaction Survey Records... notices. The amended Privacy Act system of records notice, ``COMMERCE/PAT- TM-20 Customer Call Center... name: Customer Call Center, Assistance and Satisfaction Survey Records. Security classification...

Assessment of photodynamic damage on Escherichia coli via atomic force microscopy

NASA Astrophysics Data System (ADS)

Núñez, Silvia Cristina; Simões Ribeiro, Martha; Silva Garcez, Aguinaldo; Miyakawa, Walter

2010-04-01

Photodynamic antimicrobial therapy (PAT) may become a useful clinical tool to treat microbial infections, overcoming microbial resistance that is a major problem nowadays. The aim of our work was to verify the damage caused by photosensitization over a Escherichia col) via atomic force microscopy (AFM), looking for structural changes that might occur in cells after PAT. Cells culture were grown until a stationary phase to reach a concentration of approximately 108 cells/mL allowing the production of extracellular slime in a biofilm-like structure. The cells including the extracellular matrix were put in a slide and its structure was observed using AFM; subsequently a water solution of methylene blue at 60μM was applied over the cells and a pre-irradiation time of 3 minutes was waited and followed by illumination with a diode laser (λ=660nm, power 40mW, 3min, fluence 180J/cm2, beam diameter 0.04cm2). The same cells were observed and the images stored. A second set of experiments was performed with a smaller number of cells/area and without extracellular slime, using the parameters abovementioned. The results showed alterations on cellular scaffold markedly dependent on the number of cells and the presence of extracellular slime. The slime is targeted by the photosensitizer, and after irradiation a destruction of the matrix was observed; when fewer cells were evaluated the destruction is much more evident. The images suggested rupture of the cellular membrane and cellular fragments were observed. Our findings indicate that AFM seems is a useful tool to investigate parameters linked with photodestruction of microorganisms.

Upregulation of the PatAB Transporter Confers Fluoroquinolone Resistance to Streptococcus pseudopneumoniae

PubMed Central

Alvarado, María; Martín-Galiano, Antonio J.; Ferrándiz, María J.; Zaballos, Ángel; de la Campa, Adela G.

2017-01-01

We characterized the mechanism of fluoroquinolone-resistance in two isolates of Streptococcus pseudopneumoniae having fluoroquinolone-efflux as unique mechanism of resistance. Whole genome sequencing and genetic transformation experiments were performed together with phenotypic determinations of the efflux mechanism. The PatAB pump was identified as responsible for efflux of ciprofloxacin (MIC of 4 μg/ml), ethidium bromide (MICs of 8–16 μg/ml) and acriflavine (MICs of 4–8 μg/ml) in both isolates. These MICs were at least 8-fold lower in the presence of the efflux inhibitor reserpine. Complete genome sequencing indicated that the sequence located between the promoter of the patAB operon and the initiation codon of patA, which putatively forms an RNA stem-loop structure, may be responsible for the efflux phenotype. RT-qPCR determinations performed on RNAs of cultures treated or not treated with subinhibitory ciprofloxacin concentrations were performed. While no significant changes were observed in wild-type Streptococcus pneumoniae R6 strain, increases in transcription were detected in the ciprofloxacin-efflux transformants obtained with DNA from efflux-positive isolates, in the ranges of 1.4 to 3.4-fold (patA) and 2.1 to 2.9-fold (patB). Ciprofloxacin-induction was related with a lower predicted free energy for the stem-loop structure in the RNA of S. pseudopneumoniae isolates (−13.81 and −8.58) than for R6 (−15.32 kcal/mol), which may ease transcription. The presence of these regulatory variations in commensal S. pseudopneumoniae isolates, and the possibility of its transfer to Streptococcus pneumoniae by genetic transformation, could increase fluoroquinolone resistance in this important pathogen. PMID:29123510

Education majors' expectations and reported experiences with inquiry-based physics: Implications for student affect

NASA Astrophysics Data System (ADS)

Gaffney, Jon D. H.

2013-06-01

To address a perennial need to provide K-8 teachers with a solid foundation in science, there are many physics content courses throughout the United States. One such course is Physics and Astronomy for Teachers (PAT), which relies heavily on active-learning strategies. Although PAT is successful in teaching physics content, students sometimes report dissatisfaction with the course. Such instances of poor affect are worrisome because they may influence how teachers present science in their own classrooms. Therefore, this study investigates students’ affect in terms of their pedagogical expectations and potential personal learning outcomes with respect to PAT. Two sections of PAT, each containing approximately 40 students, were observed. Students in those sections were surveyed, and a sample were interviewed (N=10). An analysis of the data in terms of an expectancy violation framework shows that while students’ expectations regarding the hands-on and interactive components of PAT were met, they received substantially fewer lectures, class discussions, and opportunities to make class presentations than they had expected, even after they had been presented with the course syllabus and informed about the specific nature of the course. Additionally, students expected PAT to be more directly linked with their future teaching careers and therefore expected more opportunities to practice teaching science than they reported receiving. This investigation serves as a case study to provide insight into why students are sometimes frustrated and confused when first encountering active-learning classes, and it implies that instructors should be cognizant of those feelings and devote resources toward explicit orientation that emphasizes the purpose of the course and reasons behind their pedagogical choices.

Successful group psychotherapy of depression in adolescents alters fronto-limbic resting-state connectivity.

PubMed

Straub, J; Metzger, C D; Plener, P L; Koelch, M G; Groen, G; Abler, B

2017-02-01

Current resting state imaging findings support suggestions that the neural signature of depression and therefore also its therapy should be conceptualized as a network disorder rather than a dysfunction of specific brain regions. In this study, we compared neural connectivity of adolescent patients with depression (PAT) and matched healthy controls (HC) and analysed pre-to-post changes of seed-based network connectivities in PAT after participation in a cognitive behavioral group psychotherapy (CBT). 38 adolescents (30 female; 19 patients; 13-18 years) underwent an eyes-closed resting-state scan. PAT were scanned before (pre) and after (post) five sessions of CBT. Resting-state functional connectivity was analysed in a seed-based approach for right-sided amygdala and subgenual anterior cingulate cortex (sgACC). Symptom severity was assessed using the Beck Depression Inventory Revision (BDI-II). Prior to group CBT, between groups amygdala and sgACC connectivity with regions of the default mode network was stronger in the patients group relative to controls. Within the PAT group, a similar pattern significantly decreased after successful CBT. Conversely, seed-based connectivity with affective regions and regions processing cognition and salient stimuli was stronger in HC relative to PAT before CBT. Within the PAT group, a similar pattern changed with CBT. Changes in connectivity correlated with the significant pre-to-post symptom improvement, and pre-treatment amygdala connectivity predicted treatment response in depressed adolescents. Sample size and missing long-term follow-up limit the interpretability. Successful group psychotherapy of depression in adolescents involved connectivity changes in resting state networks to that of healthy controls. Copyright © 2016 Elsevier B.V. All rights reserved.

P-body components, Dhh1 and Pat1, are involved in tRNA nuclear-cytoplasmic dynamics

PubMed Central

Hurto, Rebecca L.; Hopper, Anita K.

2011-01-01

The nuclear-cytoplasmic distribution of tRNA depends on the balance between tRNA nuclear export/re-export and retrograde tRNA nuclear import in Saccharomyces cerevisiae. The distribution of tRNA is sensitive to nutrient availability as cells deprived of various nutrients exhibit tRNA nuclear accumulation. Starvation induces numerous events that result in translational repression and P-body formation. This study investigated the possible coordination of these responses with tRNA nuclear-cytoplasmic distribution. Dhh1 and Pat1 function in parallel to promote translation repression and P-body formation in response to starvation. Loss of both, Dhh1 and Pat1, results in a failure to repress translation and to induce P-body formation in response to glucose starvation. This study reports that nutrient deprived dhh1 pat1 cells also fail to accumulate tRNA within nuclei. Conversely, inhibition of translation initiation and induction of P-body formation by overproduction of Dhh1 or Pat1 cause tRNA nuclear accumulation in nutrient-replete conditions. Also, loss of the mRNA decapping activator, Lsm1, causes tRNA nuclear accumulation. However, the coordination between P-body formation, translation repression, and tRNA distribution is limited to the early part of the P-body formation/translation repression pathway as loss of mRNA decapping or 5′ to 3′ degradation does not influence tRNA nuclear-cytoplasmic dynamics. The data provide the first link between P-body formation/translation initiation and tRNA nuclear-cytoplasmic dynamics. The current model is that Dhh1 and Pat1 function in parallel to promote starvation-induced tRNA nuclear accumulation. PMID:21398402

Dynamic thermal effects of epidermal melanin and plasmonic nanoparticles during photoacoustic breast imaging

NASA Astrophysics Data System (ADS)

Ghassemi, Pejhman; Wang, Quanzeng; Pfefer, T. Joshua

2016-03-01

Photoacoustic Tomography (PAT) employs high-power near-infrared (near-IR) laser pulses to generate structural and functional information on tissue chromophores up to several centimeters below the surface. Such insights may facilitate detection of breast cancer - the most common cancer in women. PAT mammography has been the subject of extensive research, including techniques based on exogenous agents for PAT contrast enhancement and molecular specificity. However, photothermal safety risks of PAT due to strong chromophores such as epidermal melanin and plasmonic nanoparticles have not been rigorously studied. We have used computational and experimental approaches to elucidate highly dynamic optical-thermal processes during PAT. A Monte Carlo model was used to simulate light propagation at 800 and 1064 nm in a multi-layer breast tissue geometry with different epidermal pigmentation levels and a tumorsimulating inclusion incorporating nanoparticles. Energy deposition results were then used in a bioheat transfer model to simulate temperature transients. Experimental measurements involved multi-layer hydrogel phantoms with inclusions incorporating gold nanoparticles. Phantom optical properties were measured using the inverse adding-doubling technique. Thermal imaging was performed as phantoms were irradiated with 5 ns near-IR pulses. Scenarios using 10 Hz laser irradiation of breast tissue containing various nanoparticle concentrations were implemented experimentally and computationally. Laser exposure levels were based on ANSI/IEC limits. Surface temperature measurements were compared to corresponding simulation data. In general, the effect of highly pigmented skin on temperature rise was significant, whereas unexpectedly small levels of temperature rise during nanoparticle irradiation were attributed to rapid photodegradation. Results provide key initial insights into light-tissue interactions impacting the safety and effectiveness of PAT.

A single haplotype hyposensitive to light and requiring strong vernalization dominates Arabidopsis thaliana populations in Patagonia, Argentina.

PubMed

Kasulin, Luciana; Rowan, Beth A; León, Rolando J C; Schuenemann, Verena J; Weigel, Detlef; Botto, Javier F

2017-07-01

The growing collection of sequenced or genotyped Arabidopsis thaliana accessions includes mostly individuals from the native Eurasian and N. African range and introduced North American populations. Here, we describe the genetic and phenotypic diversity, along with habitats and life history, of A. thaliana plants collected at the southernmost end of its worldwide distribution. Seed samples were harvested from plants growing in four sites within a ~3500-km 2 -area in Patagonia, Argentina, and represent the first germplasm to be collected in South America for this species. Whole-genome resequencing revealed that plants from the four sites and a Patagonia herbarium specimen collected in 1967 formed a single haplogroup (Pat), indicating that the phenotypic variation observed in the field reflected plastic responses to the environment. admixture and principal components analyses suggest that the ancestor of the Pat haplogroup either came from Italy or the Balkan/Caucasus regions of Eurasia. In the laboratory, plants from the Pat haplogroup were hyposensitive to continuous red (Rc) and shade light, with corresponding changes in the expression of phytochrome signalling genes. Pat had higher PIF3 and PIF5 and lower HY5 expression under Rc light; and lower expression of PIL1, ATHB2 and HFR1 under shade compared to Col-0. In addition, Pat plants had a strong vernalization requirement associated with high levels of FLC expression. We conclude that including Pat in studies of natural variation and in comparison with other introduced populations will provide additional information for association studies and allow for a more detailed assessment of the demographic events following colonization. © 2017 John Wiley & Sons Ltd.

Exercise Training Reduces Intrathoracic Fat Regardless of Defective Glucose Tolerance.

PubMed

Honkala, Sanna M; Motiani, Kumail K; Eskelinen, Jari-Joonas; Savolainen, Anna; Saunavaara, Virva; Virtanen, Kirsi A; Löyttyniemi, Eliisa; Kapanen, Jukka; Knuuti, Juhani; Kalliokoski, Kari K; Hannukainen, Jarna C

2017-07-01

Epicardial (EAT) and pericardial (PAT) fat masses and myocardial triglyceride content (MTC) are enlarged in obesity and insulin resistance. We studied whether the high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) similarly decrease ectopic fat in and around the heart and whether the decrease is similar in healthy subjects and subjects with defective glucose tolerance (DGT). A total of 28 healthy men (body mass index = 20.7-30.0 kg·m, age = 40-55 yr) and 16 men with DGT (body mass index = 23.8-33.5 kg·m, age = 43-53 yr) were randomized into HIIT and MICT interventions for 2 wk. EAT and PAT were determined by computed tomography and MTC by H-MRS. At baseline, DGT subjects had impaired aerobic capacity and insulin sensitivity and higher levels of whole body fat, visceral fat, PAT, and EAT (P < 0.05, all) compared with healthy subjects. In the whole group, HIIT increased aerobic capacity (HIIT = 6%, MICT = 0.3%; time × training P = 0.007) and tended to improve insulin sensitivity (HIIT = 24%, MICT = 8%) as well as reduce MTC (HIIT = -42%, MICT = +23%) (time × training P = 0.06, both) more efficiently compared with MICT, and without differences in the training response between the healthy and the DGT subjects. However, both training modes decreased EAT (-5%) and PAT (-6%) fat (time P < 0.05) and not differently between the healthy and the DGT subjects. Whole body fat, visceral fat, PAT, and EAT masses are enlarged in DGT. Both HIIT and MICT effectively reduce EAT and PAT in healthy and DGT subjects, whereas HIIT seems to be superior as regards improving aerobic capacity, whole-body insulin sensitivity, and MTC.

Experimental demonstration of a retro-reflective laser communication link on a mobile platform

NASA Astrophysics Data System (ADS)

Nikulin, Vladimir V.; Malowicki, John E.; Khandekar, Rahul M.; Skormin, Victor A.; Legare, David J.

2010-02-01

Successful pointing, acquisition, and tracking (PAT) are crucial for the implementation of laser communication links between ground and aerial vehicles. This technology has advantages over the traditional radio frequency communication, thus justifying the research efforts presented in this paper. The authors have been successful in the development of a high precision, agile, digitally controlled two-degree-of-freedom electromechanical system for positioning of optical instruments, cameras, telescopes, and communication lasers. The centerpiece of this system is a robotic manipulator capable of singularity-free operation throughout the full hemisphere range of yaw/pitch motion. The availability of efficient two-degree-of-freedom positioning facilitated the development of an optical platform stabilization system capable of rejecting resident vibrations with the angular and frequency range consistent with those caused by a ground vehicle moving on a rough terrain. This technology is being utilized for the development of a duplex mobile PAT system demonstrator that would provide valuable feedback for the development of practical laser communication systems intended for fleets of moving ground, and possibly aerial, vehicles. In this paper, a tracking system providing optical connectivity between stationary and mobile ground platforms is described. It utilizes mechanical manipulator to perform optical platform stabilization and initial beam positioning, and optical tracking for maintaining the line-of-sight communication. Particular system components and the challenges of their integration are described. The results of field testing of the resultant system under practical conditions are presented.

Real-time assessment of critical quality attributes of a continuous granulation process.

PubMed

Fonteyne, Margot; Vercruysse, Jurgen; Díaz, Damián Córdoba; Gildemyn, Delphine; Vervaet, Chris; Remon, Jean Paul; De Beer, Thomas

2013-02-01

There exists the intention to shift pharmaceutical manufacturing of solid dosage forms from traditional batch production towards continuous production. The currently applied conventional quality control systems, based on sampling and time-consuming off-line analyses in analytical laboratories, would annul the advantages of continuous processing. It is clear that real-time quality assessment and control is indispensable for continuous production. This manuscript evaluates strengths and weaknesses of several complementary Process Analytical Technology (PAT) tools implemented in a continuous wet granulation process, which is part of a fully continuous from powder-to-tablet production line. The use of Raman and NIR-spectroscopy and a particle size distribution analyzer is evaluated for the real-time monitoring of critical parameters during the continuous wet agglomeration of an anhydrous theophylline- lactose blend. The solid state characteristics and particle size of the granules were analyzed in real-time and the critical process parameters influencing these granule characteristics were identified. The temperature of the granulator barrel, the amount of granulation liquid added and, to a lesser extent, the powder feed rate were the parameters influencing the solid state of the active pharmaceutical ingredient (API). A higher barrel temperature and a higher powder feed rate, resulted in larger granules.

Pat Conroy's "Gutter Language": "Prince of Tides" in a Lowcountry High School.

ERIC Educational Resources Information Center

White, Robert A.

1992-01-01

Describes the controversy sparked by Pat Conroy's novel "The Prince of Tides" when it was included in a reading list for an advanced-placement eleventh grade English class. Discusses Conroy's approach to writing and his experience as an unconventional teacher. (PRA)

Test-retest reliability of pulse amplitude tonometry measures of vascular endothelial function: implications for clinical trial design.

PubMed

McCrea, Cindy E; Skulas-Ray, Ann C; Chow, Mosuk; West, Sheila G

2012-02-01

Endothelial dysfunction is an important outcome for assessing vascular health in intervention studies. However, reliability of the standard non-invasive method (flow-mediated dilation) is a significant challenge for clinical applications and multicenter trials. We evaluated the repeatability of pulse amplitude tonometry (PAT) to measure change in pulse wave amplitude during reactive hyperemia (Itamar Medical Ltd, Caesarea, Israel). Twenty healthy adults completed two PAT tests (mean interval = 19.5 days) under standardized conditions. PAT-derived measures of endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI) showed strong repeatability (intra-class correlations = 0.74 and 0.83, respectively). To guide future research, we also analyzed sample size requirements for a range of effect sizes. A crossover design powered at 0.90 requires 28 participants to detect a 15% change in RHI. Our study is the first to show that PAT measurements are repeatable in adults over an interval greater than 1 week.

Supramolecular core-shell nanoparticles for photoconductive device applications

NASA Astrophysics Data System (ADS)

Cheng, Chih-Chia; Chen, Jem-Kun; Shieh, Yeong-Tarng; Lee, Duu-Jong

2016-08-01

We report a breakthrough discovery involving supramolecular-based strategies to construct novel core-shell heterojunction nanoparticles with hydrophilic adenine-functionalized polythiophene (PAT) as the core and hydrophobic phenyl-C61-butyric acid methyl ester (PCBM) as the shell, which enables the conception of new functional supramolecular assemblies for constructing functional nanomaterials for applications in optoelectronic devices. The generated nanoparticles exhibit uniform spherical shape, well-controlled tuning of particle size with narrow size distributions, and excellent electrochemical stability in solution and the solid state owing to highly efficient energy transfer from PAT to PCBM. When the PAT/PCBM nanoparticles were fabricated into a photoconducting layer in an electronic device, the resulting device showed excellent electric conduction characteristics, including an electrically-tunable voltage-controlled switch, and high short-circuit current and open-circuit voltage. These observations demonstrate how the self-assembly of PAT/PCBM into specific nanostructures may help to promote efficient charge generation and transport processes, suggesting potential for a wide variety of applications as a promising candidate material for bulk heterojunction polymer devices.

Comprehensive vascular imaging using optical coherence tomography-based angiography and photoacoustic tomography

NASA Astrophysics Data System (ADS)

Zabihian, Behrooz; Chen, Zhe; Rank, Elisabet; Sinz, Christoph; Bonesi, Marco; Sattmann, Harald; Ensher, Jason; Minneman, Michael P.; Hoover, Erich; Weingast, Jessika; Ginner, Laurin; Leitgeb, Rainer; Kittler, Harald; Zhang, Edward; Beard, Paul; Drexler, Wolfgang; Liu, Mengyang

2016-09-01

Studies have proven the relationship between cutaneous vasculature abnormalities and dermatological disorders, but to image vasculature noninvasively in vivo, advanced optical imaging techniques are required. In this study, we imaged a palm of a healthy volunteer and three subjects with cutaneous abnormalities with photoacoustic tomography (PAT) and optical coherence tomography with angiography extension (OCTA). Capillaries in the papillary dermis that are too small to be discerned with PAT are visualized with OCTA. From our results, we speculate that the PA signal from the palm is mostly from hemoglobin in capillaries rather than melanin, knowing that melanin concentration in volar skin is significantly smaller than that in other areas of the skin. We present for the first time OCTA images of capillaries along with the PAT images of the deeper vessels, demonstrating the complementary effective imaging depth range and the visualization capabilities of PAT and OCTA for imaging human skin in vivo. The proposed imaging system in this study could significantly improve treatment monitoring of dermatological diseases associated with cutaneous vasculature abnormalities.

Sensitive and Facile Electrochemiluminescent Immunoassay for Detecting Genetically Modified Rapeseed Based on Novel Carbon Nanoparticles.

PubMed

Gao, Hongfei; Wen, Luke; Wu, Yuhua; Yan, Xiaohong; Li, Jun; Li, Xiaofei; Fu, Zhifeng; Wu, Gang

2018-05-23

A highly sensitive electrochemiluminescent (ECL) immunoassay targeting PAT/ bar protein was facilely developed for genetically modified (GM) rapeseed detection using carbon nanoparticles (CNPs) originally prepared from printer toner. In this work, CNPs linked with antibody for PAT/ bar protein were used to modify a working electrode. After an immunoreaction between the PAT/ bar protein and its antibody, the immunocomplex formed on the electrode receptor region resulted in an inhibition of electron transfer between the electrode surface and the ECL substance, thus led to a decrease of ECL response. Under the optimal conditions, the ECL responses linearly decreased as the increase of the PAT/ bar protein concentration and the GM rapeseed RF3 content in the ranges of 0.10-10 ng/mL and 0.050-1.0%, with the limits of detection of 0.050 ng/mL and 0.020% (S/N = 3). These results open a facile, sensitive, and rapid approach for the safety control of agricultural GM rape.

Quantification of optical absorption coefficient from acoustic spectra in the optical diffusive regime using photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Guo, Zijian; Favazza, Christopher; Wang, Lihong V.

2012-02-01

Photoacoustic (PA) tomography (PAT) can image optical absorption contrast with ultrasonic spatial resolution in the optical diffusive regime. Multi-wavelength PAT can noninvasively monitor hemoglobin oxygen saturation (sO2) with high sensitivity and fine spatial resolution. However, accurate quantification in PAT requires knowledge of the optical fluence distribution, acoustic wave attenuation, and detection system bandwidth. We propose a method to circumvent this requirement using acoustic spectra of PA signals acquired at two optical wavelengths. With the acoustic spectral method, the absorption coefficients of an oxygenated bovine blood phantom at 560 and 575 nm were quantified with errors of ><5%.

Stress Granule-Inducing Eukaryotic Translation Initiation Factor 4A Inhibitors Block Influenza A Virus Replication

PubMed Central

Slaine, Patrick D.; Kleer, Mariel; Smith, Nathan K.; Khaperskyy, Denys A.

2017-01-01

Eukaryotic translation initiation factor 4A (eIF4A) is a helicase that facilitates assembly of the translation preinitiation complex by unwinding structured mRNA 5′ untranslated regions. Pateamine A (PatA) and silvestrol are natural products that disrupt eIF4A function and arrest translation, thereby triggering the formation of cytoplasmic aggregates of stalled preinitiation complexes known as stress granules (SGs). Here we examined the effects of eIF4A inhibition by PatA and silvestrol on influenza A virus (IAV) protein synthesis and replication in cell culture. Treatment of infected cells with either PatA or silvestrol at early times post-infection resulted in SG formation, arrest of viral protein synthesis and failure to replicate the viral genome. PatA, which irreversibly binds to eIF4A, sustained long-term blockade of IAV replication following drug withdrawal, and inhibited IAV replication at concentrations that had minimal cytotoxicity. By contrast, the antiviral effects of silvestrol were fully reversible; drug withdrawal caused rapid SG dissolution and resumption of viral protein synthesis. IAV inhibition by silvestrol was invariably associated with cytotoxicity. PatA blocked replication of genetically divergent IAV strains, suggesting common dependence on host eIF4A activity. This study demonstrates that the core host protein synthesis machinery can be targeted to block viral replication. PMID:29258238

Progress toward Understanding Protein S-acylation: Prospective in Plants

PubMed Central

Li, Yaxiao; Qi, Baoxiu

2017-01-01

S-acylation, also known as S-palmitoylation or palmitoylation, is a reversible post-translational lipid modification in which long chain fatty acid, usually the 16-carbon palmitate, covalently attaches to a cysteine residue(s) throughout the protein via a thioester bond. It is involved in an array of important biological processes during growth and development, reproduction and stress responses in plant. S-acylation is a ubiquitous mechanism in eukaryotes catalyzed by a family of enzymes called Protein S-Acyl Transferases (PATs). Since the discovery of the first PAT in yeast in 2002 research in S-acylation has accelerated in the mammalian system and followed by in plant. However, it is still a difficult field to study due to the large number of PATs and even larger number of putative S-acylated substrate proteins they modify in each genome. This is coupled with drawbacks in the techniques used to study S-acylation, leading to the slower progress in this field compared to protein phosphorylation, for example. In this review we will summarize the discoveries made so far based on knowledge learnt from the characterization of protein S-acyltransferases and the S-acylated proteins, the interaction mechanisms between PAT and its specific substrate protein(s) in yeast and mammals. Research in protein S-acylation and PATs in plants will also be covered although this area is currently less well studied in yeast and mammalian systems. PMID:28392791

Arabidopsis ERG28 Tethers the Sterol C4-Demethylation Complex to Prevent Accumulation of a Biosynthetic Intermediate That Interferes with Polar Auxin Transport[C][W

PubMed Central

Mialoundama, Alexis Samba; Jadid, Nurul; Brunel, Julien; Di Pascoli, Thomas; Heintz, Dimitri; Erhardt, Mathieu; Mutterer, Jérôme; Bergdoll, Marc; Ayoub, Daniel; Van Dorsselaer, Alain; Rahier, Alain; Nkeng, Paul; Geoffroy, Philippe; Miesch, Michel; Camara, Bilal; Bouvier, Florence

2013-01-01

Sterols are vital for cellular functions and eukaryotic development because of their essential role as membrane constituents. Sterol biosynthetic intermediates (SBIs) represent a potential reservoir of signaling molecules in mammals and fungi, but little is known about their functions in plants. SBIs are derived from the sterol C4-demethylation enzyme complex that is tethered to the membrane by Ergosterol biosynthetic protein28 (ERG28). Here, using nonlethal loss-of-function strategies focused on Arabidopsis thaliana ERG28, we found that the previously undetected SBI 4-carboxy-4-methyl-24-methylenecycloartanol (CMMC) inhibits polar auxin transport (PAT), a key mechanism by which the phytohormone auxin regulates several aspects of plant growth, including development and responses to environmental factors. The induced accumulation of CMMC in Arabidopsis erg28 plants was associated with diagnostic hallmarks of altered PAT, including the differentiation of pin-like inflorescence, loss of apical dominance, leaf fusion, and reduced root growth. PAT inhibition by CMMC occurs in a brassinosteroid-independent manner. The data presented show that ERG28 is required for PAT in plants. Furthermore, it is accumulation of an atypical SBI that may act to negatively regulate PAT in plants. Hence, the sterol pathway offers further prospects for mining new target molecules that could regulate plant development. PMID:24326590

First Experience of Ultrasound-guided Percutaneous Ablation for Recurrent Hepatoblastoma after Liver Resection in Children

PubMed Central

Liu, Baoxian; Zhou, Luyao; Huang, Guangliang; Zhong, Zhihai; Jiang, Chunlin; Shan, Quanyuan; Xu, Ming; Kuang, Ming; Xie, Xiaoyan

2015-01-01

This study aimed to summarize the first experience with ultrasound-guided percutaneous ablation treatment (PAT) for recurrent hepatoblastoma (HB) after liver resection in children. From August 2013 to October 2014, PAT was used to treat 5 children with a total of 8 recurrent HB (mean size, 1.4 ± 0.8 cm; size range, 0.7–3.1 cm), including 4 patients with 7 tumors in the liver and 1 patient with 1 tumor in the lung. Technical success was achieved in all patients (5/5, 100%). The complete ablation rate after the first ablation session was 80% (4/5) on a patient-by-patient basis and 87.5% (7/8) on a tumor-by-tumor basis. Only 1 patient developed a fever with temperature >39 °C; it lasted 4 days after radiofrequency ablation (RFA) and was resolved by conservative therapy. During the follow-up period, new intrahepatic recurrences after PAT were detected in two patients. One died due to tumor progression 4 months after ablation. The median overall survival time after PAT was 13.8 months. PAT is a safe and promising therapy for children with recurrent HB after liver resection, and further investigation in large-scale randomized clinical trials is required to determine its role in the treatment of this disease. PMID:26578035

Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres.

PubMed

Lu, Wei; Huang, Qian; Ku, Geng; Wen, Xiaoxia; Zhou, Min; Guzatov, Dmitry; Brecht, Peter; Su, Richard; Oraevsky, Alexander; Wang, Lihong V; Li, Chun

2010-03-01

Photoacoustic tomography (PAT) also referred to as optoacoustic tomography (OAT) is a hybrid imaging modality that employs nonionizing optical radiation and ultrasonic detection. Here, we describe the application of a new class of optical contrast agents based on mesoscopic hollow gold nanospheres (HAuNS) to PAT. HAuNS are approximately 40 nm in diameter with a hollow interior and consist of a thin gold wall. They display strong resonance absorption tuned to the near-infrared (NIR) range, with an absorption peak at 800 nm, whose photoacoustic efficiency is significantly greater than that of blood. Following surface conjugation with thiolated poly(ethylene glycol), the pegylated HAuNS (PEG-HAuNS) had distribution and elimination half-lives of 1.38 +/- 0.38 and 71.82 +/- 30.46 h, respectively. Compared with PAT images based on the intrinsic optical contrast in nude mice, the PAT images acquired within 2 h after intravenous administration of PEG-HAuNS showed the brain vasculature with greater clarity and detail. The image depicted brain blood vessels as small as approximately 100 mum in diameter using PEG-HAuNS as contrast agents. Preliminary results showed no acute toxicity to the liver, spleen, or kidneys in mice following a single imaging dose of PEG-HAuNS. Our results indicate that PEG-HAuNS are promising contrast agents for PAT, with high spatial resolution and enhanced sensitivity. Copyright 2009 Elsevier Ltd. All rights reserved.

Percutaneous Aspiration Thrombectomy for the Treatment of Arterial Thromboembolic Occlusions Following Percutaneous Transluminal Angioplasty

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

Schleder, Stephan, E-mail: stephan.schleder@ukr.de; Diekmann, Matthias; Manke, Christoph

2015-02-15

PurposeThis study was designed to evaluate the technical success and the early clinical outcome of patients undergoing percutaneous aspiration thrombectomy (PAT) for the treatment of arterial thromboembolism following percutaneous infrainguinal transluminal angioplasty (PTA).MethodsIn this single-center study, during a period of 7 years retrospectively, 47 patients (22 male, 47 %) with a mean age of 73 (range 53–96) years were identified in whom PAT was performed for the treatment of thromboembolic complications of infrainguinal PTA. Primary technical success was defined as residual stenosis of <50 % in diameter after sole PAT, whereas secondary technical success was defined as residual stenosis of <50 % in diametermore » after PAT and additional PTA and/or stenting. Clinical outcome parameters (e.g., need for further intervention, minor/major amputation) were evaluated for the 30-day postinterventional period.ResultsPrimary technical success was achieved in 64 % of patients (30/47); secondary technical success was obtained in 96 % of patients (45/47). Clinical outcome data were available in 38 patients. In 87 % of patients (33/38), there was no need for further intervention within the 30-day postinterventional period. In three patients, minor amputations were conducted due to preexisting ulcerations (Rutherford Category 5 respectively).ConclusionsPAT enables endovascular treatment of iatrogenic thromboembolic complications after PTA with good technical and early clinical results and minimal morbidity.« less

Hyperspectral imaging using near infrared spectroscopy to monitor coat thickness uniformity in the manufacture of a transdermal drug delivery system.

PubMed

Pavurala, Naresh; Xu, Xiaoming; Krishnaiah, Yellela S R

2017-05-15

Hyperspectral imaging using near infrared spectroscopy (NIRS) integrates spectroscopy and conventional imaging to obtain both spectral and spatial information of materials. The non-invasive and rapid nature of hyperspectral imaging using NIRS makes it a valuable process analytical technology (PAT) tool for in-process monitoring and control of the manufacturing process for transdermal drug delivery systems (TDS). The focus of this investigation was to develop and validate the use of Near Infra-red (NIR) hyperspectral imaging to monitor coat thickness uniformity, a critical quality attribute (CQA) for TDS. Chemometric analysis was used to process the hyperspectral image and a partial least square (PLS) model was developed to predict the coat thickness of the TDS. The goodness of model fit and prediction were 0.9933 and 0.9933, respectively, indicating an excellent fit to the training data and also good predictability. The % Prediction Error (%PE) for internal and external validation samples was less than 5% confirming the accuracy of the PLS model developed in the present study. The feasibility of the hyperspectral imaging as a real-time process analytical tool for continuous processing was also investigated. When the PLS model was applied to detect deliberate variation in coating thickness, it was able to predict both the small and large variations as well as identify coating defects such as non-uniform regions and presence of air bubbles. Published by Elsevier B.V.

PAT-tools for process control in pharmaceutical film coating applications.

PubMed

Knop, Klaus; Kleinebudde, Peter

2013-12-05

Recent development of analytical techniques to monitor the coating process of pharmaceutical solid dosage forms such as pellets and tablets are described. The progress from off- or at-line measurements to on- or in-line applications is shown for the spectroscopic methods near infrared (NIR) and Raman spectroscopy as well as for terahertz pulsed imaging (TPI) and image analysis. The common goal of all these methods is to control or at least to monitor the coating process and/or to estimate the coating end point through timely measurements. Copyright © 2013 Elsevier B.V. All rights reserved.

"Computer Science Can Feed a Lot of Dreams"

ERIC Educational Resources Information Center

Educational Horizons, 2014

2014-01-01

Pat Yongpradit is the director of education at Code.org. He leads all education efforts, including professional development and curriculum creation, and he builds relationships with school districts. Pat joined "Educational Horizons" to talk about why it is important to teach computer science--even for non-computer science teachers. This…

A Tale of Two Melt Rocks: Equilibration and Metal/Sulfide-Silicate Segregation in the L7 Chondrites PAT 91501 and LEW 88663

NASA Astrophysics Data System (ADS)

Harvey, R. P.

1993-07-01

Type 7 ordinary chondrites have experienced temperatures near or beyond those necessary for partial melting. Two recently collected Antarctic specimens, PAT91501 (PAT) and LEW88663 (LEW), have been tentatively identified as L7 chondrites based on mineral and oxygen isotope compositions [1,2]. The petrology and mineralogy of these meteorites suggests that they have undergone significant metal/sulfide-silicate segregation, with implications for meteorite parent bodies. PAT consists of an equigranular contact-framework of nearly euhedral olivine grains, with interstitial spaces filled by plagioclase, pyroxenes, and several minor phases. Ortho- and clinopyroxene occur in an exsolution relationship. Olivine and pyroxene are highly equilibrated, varying <<1% in Fe-endmember content. Pyroxene equilibration temperatures calculated for PAT using the methods of [3] are self-consistent at about 1180 degrees C. In thin section, PAT contains only traces of metal, as tiny isolated blebs in sulfide grains; large (>1 cm) globular sulfide inclusions are seen in hand-sample [1], but are not present in the section examined. LEW was originally classified as an achondrite with olivine and pyroxene compositions similar to those in L chondrites [2]. Metal is absent in LEW, although the specimen is small and heavily rusted, making it impossible to gauge the original metal content. Olivine grains are commonly rounded in shape and seldom in contact with more than a few other grains. LEW olivine and pyroxene are also highly equilibrated. Veins of Ni-bearing metal oxides and sulfides are common. Both low- and high-Ca pyroxene occur as discrete grains, orthopyroxene often poikilitically enclosing olivine. Pyroxene equilibration temperatures for LEW are more variable than those for PAT and consistently lower, with an average around 900 degrees C. The various textural and compositional characteristics of PAT and LEW suggest they have experienced partial melting to varying degrees. Both visually resemble charges from experimental melting of ordinary chondrites [4-6]. The cumulate-like framework of olivine crystals in PAT suggests a high degree of partial melting, at peak temperatures sufficient to melt all other phases (above 1400 degrees C) [6]. The spheroidal sulfide nodules in PAT and the occurrence of metal (when present) only in association with sulfide strongly suggest gravitational segregation of a metal/sulfide liquid from a partial melt of the original chondritic assemblage. LEW features suggest less partial melting. Veins and grain coatings of sulfides and Fe-Ni oxides (that were probably metal before weathering) infer exposure to temperatures of 900-1000 degrees C [5]. The non-uniform olivine grain size and presence of remnant clinopyroxene grains in LEW imply that peak temperatures reached by this meteorite were not higher than 1200 degrees C [6]. The partial melting observed in PAT and LEW is probably a result of shock heating during impacts, as proposed in studies of Shaw (L7) and other similar lithologies [7]. If significant metal/sulfide-silicate segregation can occur in the relatively small volumes and short heating times associated with impact melting, even small planetesimals might be differentiated. This implies that the timescale necessary for planetary differentiation might have been significantly shortened by the assembly of already differentiated planetesimals to form meteorite parent bodies [8]. References: [1] Mason B. et al. (1992) Ant. Met. News., 15(2), 30. [2] Mason B. and Marlow R. (1992) Ant. Met. News., 15(1), 16. [3] Fonarev V. I. and Graphchikov A. A. (1991) In Progress in Metamorphic and Magmatic Petrology (L. L. Perchuk, ed.), 65-92, Cambridge University. [4] Smith B. A. and Goldstein J. I. (1977) GCA, 41, 1061-1072. [5] McSween H. Y. Jr. et al. (1978) LPS IX, 1437-1447. [6] Takahashi E. (1983) NIPR Spec. Is., 30, 168-180. [7] Taylor G. J. et al. (1979) GCA, 43, 323-337. [8] Taylor G. J. JGR, 97, 14717-14726.

Discover Supercomputer 3

NASA Image and Video Library

2017-12-08

The heart of the NASA Center for Climate Simulation (NCCS) is the “Discover” supercomputer. In 2009, NCCS added more than 8,000 computer processors to Discover, for a total of nearly 15,000 processors. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

Discover Supercomputer 2

NASA Image and Video Library

2017-12-08

The heart of the NASA Center for Climate Simulation (NCCS) is the “Discover” supercomputer. In 2009, NCCS added more than 8,000 computer processors to Discover, for a total of nearly 15,000 processors. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

Discover Supercomputer 1

NASA Image and Video Library

2017-12-08

The heart of the NASA Center for Climate Simulation (NCCS) is the “Discover” supercomputer. In 2009, NCCS added more than 8,000 computer processors to Discover, for a total of nearly 15,000 processors. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

Repair of tegmen defect using cranial particulate bone graft.

PubMed

Greene, Arin K; Poe, Dennis S

2015-01-01

Bone paté is used to repair cranial bone defects. This material contains bone-dust collected during the high-speed burring of the cranium. Clinical and experimental studies of bone dust, however, have shown that it does not have biological activity and is resorbed. We describe the use of bone paté using particulate bone graft. Particulate graft is harvested with a hand-driven brace and 16mm bit; it is not subjected to thermal injury and its large size resists resorption. Bone paté containing particulate graft is much more likely than bone dust to contain viable osteoblasts capable of producing new bone. Copyright © 2015 Elsevier Inc. All rights reserved.

Manual for automatic generation of finite element models of spiral bevel gears in mesh

NASA Technical Reports Server (NTRS)

Bibel, G. D.; Reddy, S.; Kumar, A.

1994-01-01

The goal of this research is to develop computer programs that generate finite element models suitable for doing 3D contact analysis of faced milled spiral bevel gears in mesh. A pinion tooth and a gear tooth are created and put in mesh. There are two programs: Points.f and Pat.f to perform the analysis. Points.f is based on the equation of meshing for spiral bevel gears. It uses machine tool settings to solve for an N x M mesh of points on the four surfaces, pinion concave and convex, and gear concave and convex. Points.f creates the file POINTS.OUT, an ASCI file containing N x M points for each surface. (N is the number of node points along the length of the tooth, and M is nodes along the height.) Pat.f reads POINTS.OUT and creates the file tl.out. Tl.out is a series of PATRAN input commands. In addition to the mesh density on the tooth face, additional user specified variables are the number of finite elements through the thickness, and the number of finite elements along the tooth full fillet. A full fillet is assumed to exist for both the pinion and gear.

Development of an activity-based probe for acyl-protein thioesterases

PubMed Central

Garland, Megan; Schulze, Christopher J.; Foe, Ian T.; van der Linden, Wouter A.; Child, Matthew A.

2018-01-01

Protein palmitoylation is a dynamic post-translational modification (PTM) important for cellular functions such as protein stability, trafficking, localization, and protein-protein interactions. S-palmitoylation occurs via the addition of palmitate to cysteine residues via a thioester linkage, catalyzed by palmitoyl acyl transferases (PATs), with removal of the palmitate catalyzed by acyl protein thioesterases (APTs) and palmitoyl-protein thioesterases (PPTs). Tools that target the regulators of palmitoylation–PATs, APTs and PPTs–will improve understanding of this essential PTM. Here, we describe the synthesis and application of a cell-permeable activity-based probe (ABP) that targets APTs in intact mammalian cells and the parasite Toxoplasma gondii. Using a focused library of substituted chloroisocoumarins, we identified a probe scaffold with nanomolar affinity for human APTs (HsAPT1 and HsAPT2) and synthesized a fluorescent ABP, JCP174-BODIPY TMR (JCP174-BT). We use JCP174-BT to profile HsAPT activity in situ in mammalian cells, to detect an APT in T. gondii (TgPPT1). We show discordance between HsAPT activity levels and total protein concentration in some cell lines, indicating that total protein levels may not be representative of APT activity in complex systems, highlighting the utility of this probe. PMID:29364904

75 FR 55455 - Airworthiness Directives; The Boeing Company Model 737-700 (IGW) Series Airplanes Equipped With...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-13

... modification of PATS Aircraft, LLC, auxiliary fuel tanks. This AD results from fuel system reviews conducted by... Aircraft Systems, 21652 Nanticoke Avenue, Georgetown, Delaware 19947; telephone 302-253-6157; fax 302-855... proposed to require deactivation or modification of PATS Aircraft, LLC, auxiliary fuel tanks. Comments We...

Grace and Courtesy across the Planes of Development

ERIC Educational Resources Information Center

Ludick, Pat

2015-01-01

Pat Ludick's commentary on grace and courtesy is established by a philosophical orientation to development: Grace is oriented to the life of the interior that is consciousness and being, and courtesy moves outward to daily living where civility reflects on success with human interactions. Pat's projected grace and courtesy across the planes is…

Perceptions and Lived Experiences of Illinois Parents as Teachers Program Leaders While Managing a Multigenerational Staff

ERIC Educational Resources Information Center

Ruhe Marsh, Linda

2012-01-01

The purpose of this qualitative narrative inquiry was to explore the perceptions and lived experiences of Illinois Parents as Teachers (PAT) program leaders managing a multigenerational workforce. Supervisors state that leading a multigenerational staff possesses challenges that affect overall productivity (Bell, 2008). PAT stakeholders including…

Peer-Assisted Tutoring in a Chemical Engineering Curriculum: Tutee and Tutor Experiences

ERIC Educational Resources Information Center

Kieran, Patricia; O'Neill, Geraldine

2009-01-01

Peer-Assisted Tutorials (PATs), a form of Peer-Assisted Learning (PAL), were introduced to a conventional 4-year honours degree programme in Chemical Engineering. PATs were designed to support students in becoming more self-directed in their learning, to develop student confidence in tackling Chemical Engineering problems and to promote effective…

Connective Auxin Transport in the Shoot Facilitates Communication between Shoot Apices

PubMed Central

Bennett, Tom; Hines, Geneviève; van Rongen, Martin; Sawchuk, Megan G.; Scarpella, Enrico; Ljung, Karin

2016-01-01

The bulk polar movement of the plant signaling molecule auxin through the stem is a long-recognized but poorly understood phenomenon. Here we show that the highly polar, high conductance polar auxin transport stream (PATS) is only part of a multimodal auxin transport network in the stem. The dynamics of auxin movement through stems are inconsistent with a single polar transport regime and instead suggest widespread low conductance, less polar auxin transport in the stem, which we term connective auxin transport (CAT). The bidirectional movement of auxin between the PATS and the surrounding tissues, mediated by CAT, can explain the complex auxin transport kinetics we observe. We show that the auxin efflux carriers PIN3, PIN4, and PIN7 are major contributors to this auxin transport connectivity and that their activity is important for communication between shoot apices in the regulation of shoot branching. We propose that the PATS provides a long-range, consolidated stream of information throughout the plant, while CAT acts locally, allowing tissues to modulate and be modulated by information in the PATS. PMID:27119525

Photoacoustic sentinel lymph node imaging with self-assembled copper neodecanoate nanoparticles.

PubMed

Pan, Dipanjan; Cai, Xin; Yalaz, Ceren; Senpan, Angana; Omanakuttan, Karthik; Wickline, Samuel A; Wang, Lihong V; Lanza, Gregory M

2012-02-28

Photoacoustic tomography (PAT) is emerging as a novel, hybrid, and non-ionizing imaging modality because of its satisfactory spatial resolution and high soft tissue contrast. PAT combines the advantages of both optical and ultrasonic imaging methods. It opens up the possibilities for noninvasive staging of breast cancer and may replace sentinel lymph node (SLN) biopsy in clinic in the near future. In this work, we demonstrate for the first time that copper can be used as a contrast metal for near-infrared detection of SLN using PAT. A unique strategy is adopted to encapsulate multiple copies of Cu as organically soluble small molecule complexes within a phospholipid-entrapped nanoparticle. The nanoparticles assumed a size of 80-90 nm, which is the optimum hydrodynamic diameter for its distribution throughout the lymphatic systems. These particles provided at least 6-fold higher signal sensitivity in comparison to blood, which is a natural absorber of light. We also demonstrated that high SLN detection sensitivity with PAT can be achieved in a rodent model. This work clearly demonstrates for the first time the potential use of copper as an optical contrast agent.

High-speed pre-clinical brain imaging using pulsed laser diode based photoacoustic tomography (PLD-PAT) system

NASA Astrophysics Data System (ADS)

Upputuri, Paul Kumar; Pramanik, Manojit

2016-03-01

Photoacoustic tomography (PAT) is a promising biomedical imaging modality for small animal imaging, breast cancer imaging, monitoring of vascularisation, tumor angiogenesis, blood oxygenation, total haemoglobin concentration etc. The existing PAT systems that uses Q-switched Nd:YAG and OPO nanosecond lasers have limitations in clinical applications because they are expensive, non-potable and not suitable for real-time imaging due to their low pulse repetition rate. Low-energy pulsed near-infrared diode laser which are low-cost, compact, and light-weight (<200 grams), can be used as an alternate. In this work, we present a photoacoustic tomography system with a pulsed laser diode (PLD) that can nanosecond pulses with pulse energy 1.3 mJ/pulse at ~803 nm wavelength and 7000 Hz repetition rate. The PLD is integrated inside a single-detector circular scanning geometric system. To verify the high speed imaging capabilities of the PLD-PAT system, we performed in vivo experimental results on small animal brain imaging using this system. The proposed system is portable, low-cost and can provide real-time imaging.

Continuous cuff-less blood pressure monitoring based on the pulse arrival time approach: the impact of posture.

PubMed

Muehlsteff, J; Aubert, X A; Morren, G

2008-01-01

There is an unmet need for cuff-less blood pressure (BP) monitoring especially, in personal healthcare applications. The pulse arrival time (PAT) approach might offer a suitable solution to enable comfortable BP monitoring even at beat-level. However, the methodology is based on hemodynamic surrogate measures, which are sensitive to patient activities such as posture changes, not necessarily related to blood pressure variations. In this paper, we analyze the impact of posture on the PAT measure and related hemodynamic parameters such as the pre-ejection period in well-defined procedures. Additionally, the PAT of a monitored subject is investigated in an unsupervised scenario illustrating the complexity of such a measurement. Our results show the failure of blood pressure inference based on simple calibration strategies using the PAT measure only. We discuss opportunities to compensate for the observed effects towards the realization of wearable cuff-less blood pressure monitoring. These findings emphasize the importance of accessing context information in personal healthcare applications, where vital sign monitoring is typically unsupervised.

The structure of the cyanobactin domain of unknown function from PatG in the patellamide gene cluster

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

Mann, Greg; Koehnke, Jesko; Bent, Andrew F.

The highly conserved domain of unknown function in the cyanobactin superfamily has a novel fold. The protein does not appear to bind the most plausible substrates, leaving questions as to its role. Patellamides are members of the cyanobactin family of ribosomally synthesized and post-translationally modified cyclic peptide natural products, many of which, including some patellamides, are biologically active. A detailed mechanistic understanding of the biosynthetic pathway would enable the construction of a biotechnological ‘toolkit’ to make novel analogues of patellamides that are not found in nature. All but two of the protein domains involved in patellamide biosynthesis have been characterized.more » The two domains of unknown function (DUFs) are homologous to each other and are found at the C-termini of the multi-domain proteins PatA and PatG. The domain sequence is found in all cyanobactin-biosynthetic pathways characterized to date, implying a functional role in cyanobactin biosynthesis. Here, the crystal structure of the PatG DUF domain is reported and its binding interactions with plausible substrates are investigated.« less

A Comparison of Prediction Methods for Design of Pump as Turbine for Small Hydro Plant: Implemented Plant

NASA Astrophysics Data System (ADS)

Naeimi, Hossein; Nayebi Shahabi, Mina; Mohammadi, Sohrab

2017-08-01

In developing countries, small and micro hydropower plants are very effective source for electricity generation with energy pay-back time (EPBT) less than other conventional electricity generation systems. Using pump as turbine (PAT) is an attractive, significant and cost-effective alternative. Pump manufacturers do not normally provide the characteristic curves of their pumps working as turbines. Therefore, choosing an appropriate Pump to work as a turbine is essential in implementing the small-hydro plants. In this paper, in order to find the best fitting method to choose a PAT, the results of a small-hydro plant implemented on the by-pass of a Pressure Reducing Valve (PRV) in Urmia city in Iran are presented. Some of the prediction methods of Best Efficiency Point of PATs are derived. Then, the results of implemented project have been compared to the prediction methods results and the deviation of from measured data were considered and discussed and the best method that predicts the specifications of PAT more accurately determined. Finally, the energy pay-back time for the plant is calculated.

Effect of simulated Earth reentry exposure on mechanical properties of several oxide dispersion strengthened and superalloy sheet materials

NASA Technical Reports Server (NTRS)

Whittenberger, J. D.

1977-01-01

The effects of simulated multiple reentry into the earth's atmosphere on the mechanical properties of several high temperature metallic sheet materials were evaluated. The materials included five tin-gage (nominally 0.025- or 0.037-cm) oxide dispersion strengthened (ODS) alloys and two thin-gage (nominally 0.037-cm) superalloys. Multiple reentry conditions were simulated through cyclic Plasma Arc Tunnel (PAT) exposure. PAT exposure generally consisted of 100 cycles of 600 second duration at 1255, 1366, or 1477 K in a Mach 4.6 airstream with an impact pressure of nominally 800 N/m2. PAT exposure generally produced a uniform oxide scale, oxide pits or intergranular oxidation, Kirkendall porosity, and alloy depletion zones except for the aluminum-containing ODS alloys. Only a uniform oxide scale was formed on the aluminum-containing ODS alloys. PAT exposure did not significantly affect the mechanical properties of the thin-gage (nominally 0.025- or 0.037-cm) alloys evaluated. Thus it appears that the microstructural changes produced by Plasma Arc Tunnel exposure has little influence on mechanical properties.

Optimization of turbine positioning in water distribution networks. A Sicilian case study

NASA Astrophysics Data System (ADS)

Milici, Barbara; Messineo, Simona; Messineo, Antonio

2017-11-01

The potential energy of water in Water Distribution Networks (WDNs), is usually dissipated by Pressure Reduction Valves (PRVs), thanks to which water utilities manage the pressure level in selected nodes of the network. The present study explores the use of economic hydraulic machines, pumps as turbines (PATs), to produce energy in a small network with the aim to avoid dissipation in favour of renewable energy production. The proposed study is applied to a WDN located in a town close to Palermo (Sicily), where users often install private tanks, to collect water during the period of water scarcity conditions. As expected, the economic benefit of PATs installation in WDNs is affected by the presence of private tanks, whose presence deeply modifies the network from designed condition. The analysis is carried out by means of a mathematical model, which is able to simulate dynamically water distribution networks with private tanks and PATs. As expected, the advantage of PATs' installation in terms of renewable energy recovery is strictly conditioned by their placement in the WDN.

A suite of phantom-based test methods for assessing image quality of photoacoustic tomography systems

NASA Astrophysics Data System (ADS)

Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Pfefer, T. Joshua

2017-03-01

As Photoacoustic Tomography (PAT) matures and undergoes clinical translation, objective performance test methods are needed to facilitate device development, regulatory clearance and clinical quality assurance. For mature medical imaging modalities such as CT, MRI, and ultrasound, tissue-mimicking phantoms are frequently incorporated into consensus standards for performance testing. A well-validated set of phantom-based test methods is needed for evaluating performance characteristics of PAT systems. To this end, we have constructed phantoms using a custom tissue-mimicking material based on PVC plastisol with tunable, biologically-relevant optical and acoustic properties. Each phantom is designed to enable quantitative assessment of one or more image quality characteristics including 3D spatial resolution, spatial measurement accuracy, ultrasound/PAT co-registration, uniformity, penetration depth, geometric distortion, sensitivity, and linearity. Phantoms contained targets including high-intensity point source targets and dye-filled tubes. This suite of phantoms was used to measure the dependence of performance of a custom PAT system (equipped with four interchangeable linear array transducers of varying design) on design parameters (e.g., center frequency, bandwidth, element geometry). Phantoms also allowed comparison of image artifacts, including surface-generated clutter and bandlimited sensing artifacts. Results showed that transducer design parameters create strong variations in performance including a trade-off between resolution and penetration depth, which could be quantified with our method. This study demonstrates the utility of phantom-based image quality testing in device performance assessment, which may guide development of consensus standards for PAT systems.

Pneumothorax as a Complication of Apnea Testing for Brain Death.

PubMed

Gorton, Lauren Elizabeth; Dhar, Rajat; Woodworth, Lindsey; Anand, Nitin J; Hayes, Benjamin; Ramiro, Joanna Isabelle; Kumar, Abhay

2016-10-01

Pneumothorax is an under-recognized complication of apnea testing performed as part of the neurological determination of death. It may result in hemodynamic instability or even cardiac arrest, compromising ability to declare brain death (BD) and viability of organs for transplantation. We report three cases of pneumothorax with apnea testing (PAT) and review the available literature of this phenomenon. Series of three cases supplemented with a systematic review of literature (including discussion of apnea testing in major brain death guidelines). Two patients were diagnosed with PAT due to immediate hemodynamic compromise, while the third was diagnosed many hours after BD. An additional nine cases of PAT were found in the literature. Information regarding oxygen cannula diameter was available for nine patients (range 2.3-5.3 mm), and flow rate was available for ten patients (mean 11 L/min). Pneumothorax was treated to resolution in the majority of patients (n = 8), although only six completed apnea testing following diagnosis/treatment of pneumothorax and only three patients became organ donors afterward. Review of major BD guidelines showed that although use of low oxygen flow rate (usually ≤ 6 L/min) during apnea testing is suggested, the risk of PAT was explicitly mentioned in just one. Development of PAT may adversely affect the process of BD determination and could limit the opportunity for organ donation. Each institution should have preventive measures in place.

Insulin-induced activation of glycerol-3-phosphate acyltransferase by a chiro-inositol-containing insulin mediator is defective in adipocytes of insulin-resistant, type II diabetic, Goto-Kakizaki rats.

PubMed

Farese, R V; Standaert, M L; Yamada, K; Huang, L C; Zhang, C; Cooper, D R; Wang, Z; Yang, Y; Suzuki, S; Toyota, T

1994-11-08

Type II diabetic Goto-Kakizaki (GK) rats were insulin-resistant in euglycemic-hyperinsulinemic clamp studies. We therefore examined insulin signaling systems in control Wistar and diabetic GK rats. Glycerol-3-phosphate acyltransferase (G3PAT), which is activated by headgroup mediators released from glycosyl-phosphatidylinositol (GPI), was activated by insulin in intact and cell-free adipocyte preparations of control, but not diabetic, rats. A specific chiro-inositol-containing inositol phosphoglycan (IPG) mediator, prepared from beef liver, bypassed this defect and comparably activated G3PAT in cell-free adipocyte preparations of both diabetic GK and control rats. A myo-inositol-containing IPG mediator did not activate G3PAT. Relative to control adipocytes, labeling of GPI by [3H]glucosamine was diminished by 50% and insulin failed to stimulate GPI hydrolysis in GK adipocytes. In contrast to GPI-dependent G3PAT activation, insulin-stimulated hexose transport was intact in adipocytes and soleus and gastrocnemius muscles of the GK rat, as was insulin-induced activation of mitogen-activated protein kinase and protein kinase C. We conclude that (i) chiro-inositol-containing IPG mediator activates G3PAT during insulin action, (ii) diabetic GK rats have a defect in synthesizing or releasing functional chiro-inositol-containing IPG, and (iii) defective IPG-regulated intracellular glucose metabolism contributes importantly to insulin resistance in diabetic GK rats.

Effect of Patulin from Penicillium vulpinum on the Activity of Glutathione-S-Transferase and Selected Antioxidative Enzymes in Maize

PubMed Central

Ismaiel, Ahmed A.

2017-01-01

The mycotoxin patulin (PAT) was purified from Penicillium vulpinum CM1 culture that has been isolated from a soil cultivated with maize. The effect of PAT and of a fungal culture filtrate on the activities of glutathione-S-transferase (GST) and some antioxidant enzymes viz. ascorbate peroxidase (APX), glutathione reductase (GR), dehydroascorbate reductase (DHAR) and monodehydroascorbate reductase (MDHAR) was investigated in roots and shoots of 8-day-old maize seedlings. PAT and culture filtrate caused significant reduction effects in a dose-related manner on the total GST activity. Upon application of the high PAT concentration (25 μg·mL−1) and of the concentrated fungal filtrate (100%, v/v), the reduction in GST activity of roots was 73.8–76.0% and of shoots was 60–61.7%. Conversely, significant increases in the activities of antioxidant enzymes were induced. Application of 25 μg·PAT·mL−1 increased APX, GR, DHAR, and MDHAR activity of root by 2.40-, 2.00-, 1.24-, and 2.16-fold, respectively. In shoots, the enzymatic activity was increased by 1.57-, 1.45-, 1.45-, and 1.61-fold, respectively. Similar induction values of the enzymatic activity were obtained upon application of the concentrated fungal filtrate. This is the first report describing the response of GST and antioxidant enzyme activities of plant cells to PAT toxicity. PMID:28737668

Analytical Treatment of Forecasts of Electric Energy Consumption in Latvia

NASA Astrophysics Data System (ADS)

Balodis, M.; Gavars, V.; Andersons, J.

2014-06-01

In the paper, the changes in electric energy consumption are analyzed as associated with structural changes in the Latvian economy of postsocialistic period. To the analysis, a particular approach is applied, which consists in comparison of the basic and specific electricity consumption indices in West-, Central-, and East-European states for the time span of 1990-2010, with differences and tendencies of changes revealed. Tendencies of the type are determined for the electric energy consumption in Latvia, and recommendations are given for the use of such indices in the relevant forecasts. Rakstā apskatītas elektroenerģijas patēriņa izmaiņas, kas saistītas ar Latvijas postsociālisma perioda ekonomikas strukturālām izmaiņām. Rakstā dota Latvijas galveno elektroenerģijas patēriņa indikatoru analīze, lietojot īpašu pieeju - Rietumeiropas, Centrāleiropas un Austrumeiropas valstu indikatoru salīdzinājumu. Analizēts periods no 1990. gada līdz 2010. gadam. Salīdzināti Eiropas valstu grupu īpatnējie elektroenerģijas patēriņa indikatori un noskaidrotas to atšķirības un izmaiņu tendences. Noteiktas elektroenerģijas patēriņa izmaiņu tendences Latvijā. Dotas rekomendācijas par šo indikatoru izmantošanu elektroenerģijas patēriņa prognozēšanā. 07.05.2014.

Insulin-induced activation of glycerol-3-phosphate acyltransferase by a chiro-inositol-containing insulin mediator is defective in adipocytes of insulin-resistant, type II diabetic, Goto-Kakizaki rats.

PubMed Central

Farese, R V; Standaert, M L; Yamada, K; Huang, L C; Zhang, C; Cooper, D R; Wang, Z; Yang, Y; Suzuki, S; Toyota, T

1994-01-01

Type II diabetic Goto-Kakizaki (GK) rats were insulin-resistant in euglycemic-hyperinsulinemic clamp studies. We therefore examined insulin signaling systems in control Wistar and diabetic GK rats. Glycerol-3-phosphate acyltransferase (G3PAT), which is activated by headgroup mediators released from glycosyl-phosphatidylinositol (GPI), was activated by insulin in intact and cell-free adipocyte preparations of control, but not diabetic, rats. A specific chiro-inositol-containing inositol phosphoglycan (IPG) mediator, prepared from beef liver, bypassed this defect and comparably activated G3PAT in cell-free adipocyte preparations of both diabetic GK and control rats. A myo-inositol-containing IPG mediator did not activate G3PAT. Relative to control adipocytes, labeling of GPI by [3H]glucosamine was diminished by 50% and insulin failed to stimulate GPI hydrolysis in GK adipocytes. In contrast to GPI-dependent G3PAT activation, insulin-stimulated hexose transport was intact in adipocytes and soleus and gastrocnemius muscles of the GK rat, as was insulin-induced activation of mitogen-activated protein kinase and protein kinase C. We conclude that (i) chiro-inositol-containing IPG mediator activates G3PAT during insulin action, (ii) diabetic GK rats have a defect in synthesizing or releasing functional chiro-inositol-containing IPG, and (iii) defective IPG-regulated intracellular glucose metabolism contributes importantly to insulin resistance in diabetic GK rats. PMID:7972005

Exercise Training Reduces Intrathoracic Fat Regardless of Defective Glucose Tolerance

PubMed Central

HONKALA, SANNA M.; MOTIANI, KUMAIL K.; ESKELINEN, JARI-JOONAS; SAVOLAINEN, ANNA; SAUNAVAARA, VIRVA; VIRTANEN, KIRSI A.; LÖYTTYNIEMI, ELIISA; KAPANEN, JUKKA; KNUUTI, JUHANI; KALLIOKOSKI, KARI K.; HANNUKAINEN, JARNA C.

2017-01-01

ABSTRACT Purpose Epicardial (EAT) and pericardial (PAT) fat masses and myocardial triglyceride content (MTC) are enlarged in obesity and insulin resistance. We studied whether the high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) similarly decrease ectopic fat in and around the heart and whether the decrease is similar in healthy subjects and subjects with defective glucose tolerance (DGT). Methods A total of 28 healthy men (body mass index = 20.7–30.0 kg·m−2, age = 40–55 yr) and 16 men with DGT (body mass index = 23.8–33.5 kg·m−2, age = 43–53 yr) were randomized into HIIT and MICT interventions for 2 wk. EAT and PAT were determined by computed tomography and MTC by 1H-MRS. Results At baseline, DGT subjects had impaired aerobic capacity and insulin sensitivity and higher levels of whole body fat, visceral fat, PAT, and EAT (P < 0.05, all) compared with healthy subjects. In the whole group, HIIT increased aerobic capacity (HIIT = 6%, MICT = 0.3%; time × training P = 0.007) and tended to improve insulin sensitivity (HIIT = 24%, MICT = 8%) as well as reduce MTC (HIIT = −42%, MICT = +23%) (time × training P = 0.06, both) more efficiently compared with MICT, and without differences in the training response between the healthy and the DGT subjects. However, both training modes decreased EAT (−5%) and PAT (−6%) fat (time P < 0.05) and not differently between the healthy and the DGT subjects. Conclusion Whole body fat, visceral fat, PAT, and EAT masses are enlarged in DGT. Both HIIT and MICT effectively reduce EAT and PAT in healthy and DGT subjects, whereas HIIT seems to be superior as regards improving aerobic capacity, whole-body insulin sensitivity, and MTC. PMID:28628064

The yeast cytoplasmic LsmI/Pat1p complex protects mRNA 3' termini from partial degradation.

PubMed Central

He, W; Parker, R

2001-01-01

A key aspect of understanding eukaryotic gene regulation will be the identification and analysis of proteins that bind mRNAs and control their function. Recently, a complex of seven Lsm proteins and the Pat1p have been shown to interact with yeast mRNAs and promote mRNA decapping. In this study we present several observations to indicate that the LsmI/Pat1 complex has a second distinct function in protecting the 3'-UTR of mRNAs from trimming. First, mutations in the LSM1 to LSM7, as well as PAT1, genes led to the accumulation of MFA2pG and PGK1pG transcripts that had been shortened by 10-20 nucleotides at their 3' ends (referred to as trimming). Second, the trimming of these mRNAs was more severe at the high temperature, correlating with the inability of these mutant strains to grow at high temperature. In contrast, trimming did not occur in a dcp1 Delta strain, wherein the decapping enzyme is lacking. This indicates that trimming is not simply a consequence of the inhibition of mRNA decapping. Third, the temperature-sensitive growth of lsm and pat1 mutants was suppressed by mutations in the exosome or the functionally related Ski proteins, which are required for efficient 3' to 5' mRNA degradation of mRNA. Moreover, in lsm ski double mutants, higher levels of the trimmed mRNAs accumulated, indicating that exosome function is not required for mRNA trimming but that the exosome does degrade the trimmed mRNAs. These results raise the possibility that the temperature-sensitive growth of the lsm1-7 and pat1 mutants is at least partially due to mRNA trimming, which either inactivates the function of the mRNAs or makes them available for premature 3' to 5' degradation by the exosome. PMID:11514438

In vitro exposure of Penicillium mycotoxins with or without a modified yeast cell wall extract (mYCW) on bovine macrophages (BoMacs).

PubMed

Oh, Se-Young; Quinton, V Margaret; Boermans, Herman J; Swamy, H V L N; Karrow, Niel A

2015-11-01

Penicillium mycotoxins (PMs) are contaminants that are frequently found in grain or crop-based silage for animal feed. Previously, we have characterized the potential immunotoxicity of the following PMs: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA), and penicillic acid (PA) by using a bovine macrophage cell line (BoMacs). In the present study, cell proliferation was used as a bioassay endpoint to evaluate the efficacy of a modified yeast cell wall extract (mYCW), for preventing PM toxicity under various in vitro conditions such as the following: pH (3, 5, 7), incubation time (1, 2, 4, 6 h), percentage of mYCW (0.05, 0.1, 0.2, 0.5, 1.0 %), and PM concentration. mYCW was most effective in preventing the toxicity of 12.88 and 25.8 μM OTA at pH 3.0 (p < 0.0001), regardless of incubation time (p < 0.0001) and the percentage of mYCW (p < 0.0001). An incubation time of 6 h (p < 0.05) or 0.5 and 1.0 % mYCW (p < 0.0001) significantly improved the efficacy of mYCW for preventing CIT toxicity. In contrast, 0.5 and 1.0 % of mYCW appeared to exacerbate the PAT toxicity (p < 0. 0001). This effect on PAT toxicity was constantly observed with higher PAT concentrations, and it reached significance at a concentration of 0.70 μM (p < 0.0001). mYCW had no effect on PA toxicity. These results suggest that mYCW may reduce OTA toxicity and, to some extent, CIT toxicity at pH 3.0. Although PAT toxicity was increased by mYCW treatment, PAT is readily degraded during heat treatment and may therefore be dealt with using other preventative measures.

Effects of a pre-moistened multilayered breathable fabric in promoting heat loss during recovery after exercise under hot conditions.

PubMed

Foreman, J H; Benson, G J; Foreman, M H

2006-08-01

Horses generate considerable internal heat burdens when exercising. Although common practice for a trainer or groom to place a wet blanket or towel on the dorsum of a hot horse post exercise, there are no data supporting the efficacy of this cooling method. To test the hypothesis that a pre-moistened blanket designed with a multilayered breathable fabric would enhance heat loss in horses post exercise. Eight treadmill-trained horses performed a standardised exercise test (SET) weekly for 3 weeks, with 3 different recovery treatments administered randomly. Pulmonary artery temperature (PAT) was measured via Swan-Ganz catheter. The SET consisted of 10 min at 3.7 m/sec, 3 min at 11.0 m/sec, 25 min at 3.7 m/sec and 20 min of recovery walking at 2.0 m/sec (58 min exercise and recovery under laboratory conditions of 35.0-40.6 degrees C and 27-49% RH). From 3-7 min during recovery, the treadmill was stopped and horses randomly received either: (a) no bath (negative control); (b) a bath consisting of 32 l of 1-4 degrees C water split into 3-4 cycles of bilateral water application (positive control) followed by water removal ('scraping'); or (c) application of a multilayered fabric blanket soaked in 16-19 degrees C water, wrung out, and placed over the dorsum and sides of the horse. PAT was compared using RM ANOVA with the Student Neuman-Keul's test used post hoc to discriminate between treatments at specific points in time. Mean PAT rose with each phase of exercise (P<0.001) and peaked at a mean of 40.2 +/- 0.2 degrees C. During recovery, the cold bath decreased HR and PAT for 9 min after walking resumed (P<0.001-P<0.05). The blanket did not decrease HR or PAT compared to negative control (P>0.05), and both were hotter than the cold bath treatment through 16 min of recovery (P<0.05). A specially-designed cooling blanket failed to reduce PAT when compared to negative control. Cold water bathing decreased HR and PAT but was not effective throughout all of recovery. A specially-designed, pre-moistened multilayered breathable fabric failed to promote evaporative cooling compared to negative control. Cold water baths may need to be repeated throughout recovery to optimise their effect.

[Alcohol-purification technology and its particle sedimentation process in manufactory of Fufang Kushen injection].

PubMed

Liu, Xiaoqian; Tong, Yan; Wang, Jinyu; Wang, Ruizhen; Zhang, Yanxia; Wang, Zhimin

2011-11-01

Fufang Kushen injection was selected as the model drug, to optimize its alcohol-purification process and understand the characteristics of particle sedimentation process, and to investigate the feasibility of using process analytical technology (PAT) on traditional Chinese medicine (TCM) manufacturing. Total alkaloids (calculated by matrine, oxymatrine, sophoridine and oxysophoridine) and macrozamin were selected as quality evaluation markers to optimize the process of Fufang Kushen injection purification with alcohol. Process parameters of particulate formed in the alcohol-purification, such as the number, density and sedimentation velocity, were also determined to define the sedimentation time and well understand the process. The purification process was optimized as that alcohol is added to the concentrated extract solution (drug material) to certain concentration for 2 times and deposited the alcohol-solution containing drug-material to sediment for some time, i.e. 60% alcohol deposited for 36 hours, filter and then 80% -90% alcohol deposited for 6 hours in turn. The content of total alkaloids was decreased a little during the depositing process. The average settling time of particles with the diameters of 10, 25 microm were 157.7, 25.2 h in the first alcohol-purified process, and 84.2, 13.5 h in the second alcohol-purified process, respectively. The optimized alcohol-purification process remains the marker compositions better and compared with the initial process, it's time saving and much economy. The manufacturing quality of TCM-injection can be controlled by process. PAT pattern must be designed under the well understanding of process of TCM production.

Applications of Raman Spectroscopy in Biopharmaceutical Manufacturing: A Short Review.

PubMed

Buckley, Kevin; Ryder, Alan G

2017-06-01

The production of active pharmaceutical ingredients (APIs) is currently undergoing its biggest transformation in a century. The changes are based on the rapid and dramatic introduction of protein- and macromolecule-based drugs (collectively known as biopharmaceuticals) and can be traced back to the huge investment in biomedical science (in particular in genomics and proteomics) that has been ongoing since the 1970s. Biopharmaceuticals (or biologics) are manufactured using biological-expression systems (such as mammalian, bacterial, insect cells, etc.) and have spawned a large (>€35 billion sales annually in Europe) and growing biopharmaceutical industry (BioPharma). The structural and chemical complexity of biologics, combined with the intricacy of cell-based manufacturing, imposes a huge analytical burden to correctly characterize and quantify both processes (upstream) and products (downstream). In small molecule manufacturing, advances in analytical and computational methods have been extensively exploited to generate process analytical technologies (PAT) that are now used for routine process control, leading to more efficient processes and safer medicines. In the analytical domain, biologic manufacturing is considerably behind and there is both a huge scope and need to produce relevant PAT tools with which to better control processes, and better characterize product macromolecules. Raman spectroscopy, a vibrational spectroscopy with a number of useful properties (nondestructive, non-contact, robustness) has significant potential advantages in BioPharma. Key among them are intrinsically high molecular specificity, the ability to measure in water, the requirement for minimal (or no) sample pre-treatment, the flexibility of sampling configurations, and suitability for automation. Here, we review and discuss a representative selection of the more important Raman applications in BioPharma (with particular emphasis on mammalian cell culture). The review shows that the properties of Raman have been successfully exploited to deliver unique and useful analytical solutions, particularly for online process monitoring. However, it also shows that its inherent susceptibility to fluorescence interference and the weakness of the Raman effect mean that it can never be a panacea. In particular, Raman-based methods are intrinsically limited by the chemical complexity and wide analyte-concentration-profiles of cell culture media/bioprocessing broths which limit their use for quantitative analysis. Nevertheless, with appropriate foreknowledge of these limitations and good experimental design, robust analytical methods can be produced. In addition, new technological developments such as time-resolved detectors, advanced lasers, and plasmonics offer potential of new Raman-based methods to resolve existing limitations and/or provide new analytical insights.

Resistance to glufosinate is proportional to phosphinothricin acetyltransferase expression and activity in LibertyLink® and WideStrike® Cotton

USDA-ARS?s Scientific Manuscript database

LibertyLink® cotton cultivars are engineered for glufosinate resistance by overexpressing the bar gene that encodes phosphinothricin acetyltransferase (PAT), whereas the insect-resistant WideStrike® cultivars were obtained by using the similar pat gene as a selectable marker. The latter cultivars ca...

Teacher's PAT? Multiple-Role Principal-Agent Theory, Education Politics, and Bureaucrat Power

ERIC Educational Resources Information Center

Vanhuysse, Pieter; Sulitzeanu-Kenan, Raanan

2009-01-01

This article aims to contribute to current debates about political power and agency relationships in education and other public sectors. In a recent clarion call for a major redirection of political principal-agent theories (PAT), Terry Moe has argued that standard information asymmetries ought no longer to be regarded as the sole foundation of…

The phylogenetic placement of Picoa, with a first report on Picoa lefebvrei (Pat.) Maire (=Phaeangium lefebvrei) from Iran

Treesearch

A. Ammarellou; M.E. Smith; M.A. Tajick; J.M. Trappe

2011-01-01

Desert truffles, hypogeous Pezizales (Ascomycota), are difficult to identify due to evolutionary convergence of morphological characters among taxa that share a similar habitat and mode of spore dispersal. In this paper we document the presence of Picoa lefebvrei (Pat.) Maire (=Phaeangium lefebvrei) in Iran and use phylogenetic...

Investigating Trauma in Narrating World War I: A Psychoanalytical Reading of Pat Barker's "Regeneration"

ERIC Educational Resources Information Center

Sadjadi, Bakhtiar; Esmkhani, Farnaz

2016-01-01

The present paper seeks to critically read Pat Barker's "Regeneration" in terms of Cathy Caruth's psychoanalytic study of trauma. This analysis attempts to trace the concepts of latency, post-traumatic stress disorders, traumatic memory, and trauma in Barker's novel in order to explore how trauma and history are interrelated in the…

Efficacy and Safety of Immediate-Release Methylphenidate Treatment for Preschoolers with ADHD

ERIC Educational Resources Information Center

Greenhill, Laurence; Kollins, Scott; Abikoff, Howard; McCracken, James; Riddle, Mark; Swanson, James; McGough, James; Wigal, Sharon; Wigal, Tim; Vitiello, Benedetto; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Cunningham, Charles; Davies, Mark; Chuang, Shirley; Cooper, Tom

2006-01-01

Objective: The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD). Method: The 8-phase, 70-week PATS protocol included…

A Poetry Workshop in Print: Pat Mora

ERIC Educational Resources Information Center

Hopkins, Lee Bennett

2006-01-01

After a successful career as a writer for adults, Pat Mora began creating books for children. Her first picture book, "Tomas and The Library Lady" (Knopf, 1997) is a tender story of a young migrant worker who unearths new worlds when he discovers the magic a public library holds. The text, cleverly interspersed with foreign words, became a…

Perceived self-orientation and self-motion in microgravity, after landing and during preflight adaptation training

NASA Technical Reports Server (NTRS)

Harm, D. L.; Parker, D. E.

1993-01-01

The research described in this paper is intended to support development and evaluation of preflight adaptation training (PAT) apparatus and procedures. Successful training depends on appropriate manipulation of visual and inertial stimuli that control perception of self-motion and self-orientation. For one part of this process, astronauts are trained to report their self-motion and self-orientation experiences. Before their space mission, they are exposed to the altered sensory environments produced by the PAT trainers. During and after the mission, they report their motion and orientation experiences. Subsequently, they are again exposed to the PAT trainers and are asked to describe relationships between their experiences in microgravity and following entry and their experiences in the trainers.

Total protein of whole saliva as a biomarker of anaerobic threshold.

PubMed

Bortolini, Miguel Junior Sordi; De Agostini, Guilherme Gularte; Reis, Ismair Teodoro; Lamounier, Romeu Paulo Martins Silva; Blumberg, Jeffrey B; Espindola, Foued Salmen

2009-09-01

Saliva provides a convenient and noninvasive matrix for assessing specific physiological parameters, including some biomarkers of exercise. We investigated whether the total protein concentration of whole saliva (TPWS) would reflect the anaerobic threshold during an incremental exercise test. After a warm-up period, 13 nonsmoking men performed a maximum incremental exercise on a cycle ergometer. Blood and stimulated saliva were collected during the test. The TPWS anaerobic threshold (PAT) was determined using the Dmax method. The PAT was correlated with the blood lactate anaerobic threshold (AT; r = .93, p < .05). No significant difference (p = .16) was observed between PAT and AT. Thus, TPWS provides a convenient and noninvasive matrix for determining the anaerobic threshold during incremental exercise tests.

Design of high energy laser pulse delivery in a multimode fiber for photoacoustic tomography.

PubMed

Ai, Min; Shu, Weihang; Salcudean, Tim; Rohling, Robert; Abolmaesumi, Purang; Tang, Shuo

2017-07-24

In photoacoustic tomography (PAT), delivering high energy pulses through optical fiber is critical for achieving high quality imaging. A fiber coupling scheme with a beam homogenizer is demonstrated for coupling high energy pulses in a single multimode fiber. This scheme can benefit PAT applications that require miniaturized illumination or internal illumination with a small fiber. The beam homogenizer is achieved by using a cross cylindrical lens array, which provides a periodic spatial modulation on the phase of the input light. Thus the lens array acts as a phase grating which diffracts the beam into a 2D diffraction pattern. Both theoretical analysis and experiments demonstrate that the focused beam can be split into a 2D spot array that can reduce the peak power on the fiber tip surface and thus enhance the coupling performance. The theoretical analysis of the intensity distribution of the focused beam is carried out by Fourier optics. In experiments, coupled energy at 48 mJ/pulse and 60 mJ/pulse have been achieved and the corresponding coupling efficiency is 70% and 90% in a 1000-μm and a 1500-μm-core-diameter fiber, respectively. The high energy pulses delivered by the multimode fiber are further tested for PAT imaging in phantoms. PAT imaging of a printed dot array shows a large illumination area of 7 cm 2 under 5 mm thick chicken breast tissue. In vivo imaging is also demonstrated on the human forearm. The large improvement in coupling energy can potentially benefit PAT with single fiber delivery to achieve large area imaging and deep penetration detection.

Quantifying Beetle-Mediated Effects on Gas Fluxes from Dung Pats

PubMed Central

Penttilä, Atte; Slade, Eleanor M.; Simojoki, Asko; Riutta, Terhi; Minkkinen, Kari; Roslin, Tomas

2013-01-01

Agriculture is one of the largest contributors of the anthropogenic greenhouse gases (GHGs) responsible for global warming. Measurements of gas fluxes from dung pats suggest that dung is a source of GHGs, but whether these emissions are modified by arthropods has not been studied. A closed chamber system was used to measure the fluxes of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) from dung pats with and without dung beetles on a grass sward. The presence of dung beetles significantly affected the fluxes of GHGs from dung pats. Most importantly, fresh dung pats emitted higher amounts of CO2 and lower amounts of CH4 per day in the presence than absence of beetles. Emissions of N2O showed a distinct peak three weeks after the start of the experiment – a pattern detected only in the presence of beetles. When summed over the main grazing season (June–July), total emissions of CH4 proved significantly lower, and total emissions of N2O significantly higher in the presence than absence of beetles. While clearly conditional on the experimental conditions, the patterns observed here reveal a potential impact of dung beetles on gas fluxes realized at a small spatial scale, and thereby suggest that arthropods may have an overall effect on gas fluxes from agriculture. Dissecting the exact mechanisms behind these effects, mapping out the range of conditions under which they occur, and quantifying effect sizes under variable environmental conditions emerge as key priorities for further research. PMID:23940758

Tests of gravity Using Lunar Laser Ranging

NASA Technical Reports Server (NTRS)

Merkowitz, Stephen M.

2010-01-01

Lunar laser ranging (LLR) has been a workhorse for testing general relativity over the pat four decades. The three retrorefiector arrays put on the Moon by the Apollo astronauts and the French built array on the second Soviet Lunokhod rover continue to be useful targets, and have provided the most stringent tests of the Strong Equivalence Principle and the time variation of Newton's gravitational constant. The relatively new ranging system at the Apache Point :3.5 meter telescope now routinely makes millimeter level range measurements. Incredibly. it has taken 40 years for ground station technology to advance to the point where characteristics of the lunar retrorefiectors are limiting the precision of the range measurements. In this article. we review the gravitational science and technology of lunar laser ranging and discuss prospects for the future.

10. GLASS, SCHNEIDER & REZNER BRIDGE PATENT MODEL, PAT. NO. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. GLASS, SCHNEIDER & REZNER BRIDGE PATENT MODEL, PAT. NO. 71, 868, DECEMBER 10, 1867. THIS MODEL IS ONE OF A FEW THAT SURVIVED THE PATENT OFFICE FIRE OF 1877. IF REPRODUCED, CREDIT SHOULD BE GIVEN TO THE SMITHSONIAN INSTITUTION, NEGATIVE NO. 48660-D. - White Bowstring Arch Truss Bridge, Spanning Yellow Creek at Cemetery Drive (Riverside Drive), Poland, Mahoning County, OH

CaMKII-MEDIATED PHOSPHORYLATION OF THE BOMBYX MORI LIPID STORAGE DROPLET PROTEIN-1 (BmLsd1), AN INSECT PAT FAMILY PROTEIN, IS ESSENTIAL FOR SILKMOTH SEX PHEROMONE BIOSYNTHESIS

USDA-ARS?s Scientific Manuscript database

The structurally-related members of the PAT family of proteins, which are so name based on similarity amongst perilipin, adipophilin/adipocyte differentiation-related protein (ADRP), and tail-interacting protein of 47 kilodaltons (TIP47), are cytoplasmic lipid droplet (LD)-associated proteins charac...

Pat Thiel talks about attending the Nobel Prize Award Ceremony

ScienceCinema

Thiel, Pat

2018-05-07

Pat Thiel, Ames Laboratory senior scientist and Iowa State University Distinguished Professor of Chemistry, was invited to be a guest at the ceremony on December 10th, in Stockholm, Sweden, where Danny Shechtman, Ames Laboratory scientist, received the 2011 Nobel Prize in Chemistry. Following her return to the Lab, Thiel shared some of her recollections of the momentous event.

Design and Fabrication of Cryostat Interface and Electronics for High Performance Antimatter Trap (HI-PAT)

NASA Technical Reports Server (NTRS)

Smith, Gerald A.

1999-01-01

Included in Appendix I to this report is a complete set of design and assembly schematics for the high vacuum inner trap assembly, cryostat interfaces and electronic components for the MSFC HI-PAT. Also included in the final report are summaries of vacuum tests, and electronic tests performed upon completion of the assembly.

Pat Thiel talks about attending the Nobel Prize Award Ceremony

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

Thiel, Pat

2012-01-01

Pat Thiel, Ames Laboratory senior scientist and Iowa State University Distinguished Professor of Chemistry, was invited to be a guest at the ceremony on December 10th, in Stockholm, Sweden, where Danny Shechtman, Ames Laboratory scientist, received the 2011 Nobel Prize in Chemistry. Following her return to the Lab, Thiel shared some of her recollections of the momentous event.

Survival of Campylobacter spp. in bovine faeces on pasture.

PubMed

Gilpin, B J; Robson, B; Scholes, P; Nourozi, F; Sinton, L W

2009-02-01

To determine the survival on pasture of Campylobacter spp. naturally present in bovine faeces and compare this with a previously published study using laboratory-cultured Campylobacter spp. Ten freshly collected cow pats were deposited on pasture during summer, and Campylobacter spp. were enumerated by enrichment broth culture. The counts in three pats were below detection limits. Counts of Campylobacter spp. in the other seven pats fell below detection limits within 14 days. The geometric means of the counts up to 7 days produced a T(90) of 2.2 days. Characterization of Campylobacter spp. by PCR and pulsed field gel electrophoresis indicated the presence of at least six genotypes of Campylobacter jejuni, Campylobacter coli and Campylobacter lari. Campylobacter spp. naturally present in cow faeces exhibited a similar survival rate to that previously determined using laboratory-cultured strains. The highly variable counts of naturally occurring Campylobacter spp., and the predominance of lower counts, also support the earlier decision to use laboratory-cultured strains in survival experiments. This study reaffirms the short survival of Campylobacter spp. in cow faeces deposited on pasture. This information will be incorporated into a 'reservoir model' for Campylobacter spp. in cow pats on New Zealand pastures.

Surface molecularly imprinted polymer capped Mn-doped ZnS quantum dots as a phosphorescent nanosensor for detecting patulin in apple juice.

PubMed

Zhang, Wengang; Han, Yong; Chen, Xiumei; Luo, Xueli; Wang, Jianlong; Yue, Tianli; Li, Zhonghong

2017-10-01

A Mn-doped ZnS quantum dots (QDs) based nanosensor for selective phosphorescent determination of patulin (PAT) was synthesized with 6-hydroxynicotinic acid (6-HNA) as dummy template via a surface molecular imprinting sol-gel process. FTIR and XRD indicated the successful graft of molecularly imprinted polymer (MIP) onto crystal QDs. Binding tests revealed that the MIP-QDs presented higher selectivity, adsorption capacity and mass transfer rate than non-imprinted polymers, demonstrating a specific recognition for PAT among competitive mycotoxins and its analogues with the imprinting factor of 2.02. The MIP-QDs could recognize PAT in a linear range of 0.43-6.50μmolL -1 with a detection limit of 0.32μmolL -1 and a correlation coefficient (R 2 ) of 0.9945. Recoveries of 102.9-127.2% with relative standard deviations <4.95% were achieved in apple juice samples which were in good agreement with high-performance liquid chromatography (HPLC) (P>0.05). The results indicated a simple phosphorescent nanosensor for PAT detection in complex matrix. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inverse transport problems in quantitative PAT for molecular imaging

NASA Astrophysics Data System (ADS)

Ren, Kui; Zhang, Rongting; Zhong, Yimin

2015-12-01

Fluorescence photoacoustic tomography (fPAT) is a molecular imaging modality that combines photoacoustic tomography with fluorescence imaging to obtain high-resolution imaging of fluorescence distributions inside heterogeneous media. The objective of this work is to study inverse problems in the quantitative step of fPAT where we intend to reconstruct physical coefficients in a coupled system of radiative transport equations using internal data recovered from ultrasound measurements. We derive uniqueness and stability results on the inverse problems and develop some efficient algorithms for image reconstructions. Numerical simulations based on synthetic data are presented to validate the theoretical analysis. The results we present here complement these in Ren K and Zhao H (2013 SIAM J. Imaging Sci. 6 2024-49) on the same problem but in the diffusive regime.

Rapid and noncontact photoacoustic tomography imaging system using an interferometer with high-speed phase modulation technique

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

Liu, Jun; Tang, Zhilie; Wu, Yongbo

2015-04-15

We designed, fabricated, and tested a rapid and noncontact photoacoustic tomography (PAT) imaging system using a low-coherence interferometer with high-speed phase modulation technique. Such a rapid and noncontact probing system can greatly decrease the time of imaging. The proposed PAT imaging system is experimentally verified by capturing images of a simulated tissue sample and the blood vessels within the ear flap of a mouse (pinna) in vivo. The axial and lateral resolutions of the system are evaluated at 45 and ∼15 μm, respectively. The imaging depth of the system is 1 mm in a special phantom. Our results show thatmore » the proposed system opens a promising way to realize noncontact, real-time PAT.« less

On-line multiple component analysis for efficient quantitative bioprocess development.

PubMed

Dietzsch, Christian; Spadiut, Oliver; Herwig, Christoph

2013-02-20

On-line monitoring devices for the precise determination of a multitude of components are a prerequisite for fast bioprocess quantification. On-line measured values have to be checked for quality and consistency, in order to extract quantitative information from these data. In the present study we characterized a novel on-line sampling and analysis device comprising an automatic photometric robot. We connected this on-line device to a bioreactor and concomitantly measured six components (i.e. glucose, glycerol, ethanol, acetate, phosphate and ammonium) during different batch cultivations of Pichia pastoris. The on-line measured data did not show significant deviations from off-line taken samples and were consequently used for incremental rate and yield calculations. In this respect we highlighted the importance of data quality and discussed the phenomenon of error propagation. On-line calculated rates and yields depicted the physiological responses of the P. pastoris cells in unlimited and limited cultures. A more detailed analysis of the physiological state was possible by considering the off-line determined biomass dry weight and the calculation of specific rates. Here we present a novel device for on-line monitoring of bioprocesses, which ensures high data quality in real-time and therefore refers to a valuable tool for Process Analytical Technology (PAT). Copyright © 2012 Elsevier B.V. All rights reserved.

Development of a New Punch Head Shape to Replicate Scale-Up Issues on a Laboratory Tablet Press III: Replicating sticking phenomenon using the SAS punch and evaluation by checking the tablet surface using 3D laser scanning microscope.

PubMed

Ito, Manabu; Aoki, Shigeru; Uchiyama, Jumpei; Yamato, Keisuke

2018-04-20

Sticking is a common observation in the scale-up stage on the punch tip using a commercial tableting machine. The difference in the total compression time between a laboratory and a commercial tableting machine is considered one of the main root causes of scale up issues in the tableting processes. The proposed Size Adjusted for Scale-up (SAS) punch can be used to adjust the consolidation and dwell times for commercial tableting machine. As a result, the sticking phenomenon is able to be replicated at the pilot scale stage. As reported in this paper, the quantification of sticking was measured using a 3D laser scanning microscope to check the tablet surface. It was shown that the sticking area decreased with the addition of magnesium stearate in the formulation, but the sticking depth was not affected by the additional amount of magnesium stearate. It is proposed that use of a 3D laser scanning microscope can be applied to evaluate sticking as a process analytical technology (PAT) tool and so sticking can be monitored continuously without stopping the machine. Copyright © 2018. Published by Elsevier Inc.

Optimal design of groundwater remediation system using a probabilistic multi-objective fast harmony search algorithm under uncertainty

NASA Astrophysics Data System (ADS)

Luo, Qiankun; Wu, Jianfeng; Yang, Yun; Qian, Jiazhong; Wu, Jichun

2014-11-01

This study develops a new probabilistic multi-objective fast harmony search algorithm (PMOFHS) for optimal design of groundwater remediation systems under uncertainty associated with the hydraulic conductivity (K) of aquifers. The PMOFHS integrates the previously developed deterministic multi-objective optimization method, namely multi-objective fast harmony search algorithm (MOFHS) with a probabilistic sorting technique to search for Pareto-optimal solutions to multi-objective optimization problems in a noisy hydrogeological environment arising from insufficient K data. The PMOFHS is then coupled with the commonly used flow and transport codes, MODFLOW and MT3DMS, to identify the optimal design of groundwater remediation systems for a two-dimensional hypothetical test problem and a three-dimensional Indiana field application involving two objectives: (i) minimization of the total remediation cost through the engineering planning horizon, and (ii) minimization of the mass remaining in the aquifer at the end of the operational period, whereby the pump-and-treat (PAT) technology is used to clean up contaminated groundwater. Also, Monte Carlo (MC) analysis is employed to evaluate the effectiveness of the proposed methodology. Comprehensive analysis indicates that the proposed PMOFHS can find Pareto-optimal solutions with low variability and high reliability and is a potentially effective tool for optimizing multi-objective groundwater remediation problems under uncertainty.

Hybrid modeling as a QbD/PAT tool in process development: an industrial E. coli case study.

PubMed

von Stosch, Moritz; Hamelink, Jan-Martijn; Oliveira, Rui

2016-05-01

Process understanding is emphasized in the process analytical technology initiative and the quality by design paradigm to be essential for manufacturing of biopharmaceutical products with consistent high quality. A typical approach to developing a process understanding is applying a combination of design of experiments with statistical data analysis. Hybrid semi-parametric modeling is investigated as an alternative method to pure statistical data analysis. The hybrid model framework provides flexibility to select model complexity based on available data and knowledge. Here, a parametric dynamic bioreactor model is integrated with a nonparametric artificial neural network that describes biomass and product formation rates as function of varied fed-batch fermentation conditions for high cell density heterologous protein production with E. coli. Our model can accurately describe biomass growth and product formation across variations in induction temperature, pH and feed rates. The model indicates that while product expression rate is a function of early induction phase conditions, it is negatively impacted as productivity increases. This could correspond with physiological changes due to cytoplasmic product accumulation. Due to the dynamic nature of the model, rational process timing decisions can be made and the impact of temporal variations in process parameters on product formation and process performance can be assessed, which is central for process understanding.

An advanced search engine for patent analytics in medicinal chemistry.

PubMed

Pasche, Emilie; Gobeill, Julien; Teodoro, Douglas; Gaudinat, Arnaud; Vishnykova, Dina; Lovis, Christian; Ruch, Patrick

2012-01-01

Patent collections contain an important amount of medical-related knowledge, but existing tools were reported to lack of useful functionalities. We present here the development of TWINC, an advanced search engine dedicated to patent retrieval in the domain of health and life sciences. Our tool embeds two search modes: an ad hoc search to retrieve relevant patents given a short query and a related patent search to retrieve similar patents given a patent. Both search modes rely on tuning experiments performed during several patent retrieval competitions. Moreover, TWINC is enhanced with interactive modules, such as chemical query expansion, which is of prior importance to cope with various ways of naming biomedical entities. While the related patent search showed promising performances, the ad-hoc search resulted in fairly contrasted results. Nonetheless, TWINC performed well during the Chemathlon task of the PatOlympics competition and experts appreciated its usability.

A user-friendly tool for medical-related patent retrieval.

PubMed

Pasche, Emilie; Gobeill, Julien; Teodoro, Douglas; Gaudinat, Arnaud; Vishnyakova, Dina; Lovis, Christian; Ruch, Patrick

2012-01-01

Health-related information retrieval is complicated by the variety of nomenclatures available to name entities, since different communities of users will use different ways to name a same entity. We present in this report the development and evaluation of a user-friendly interactive Web application aiming at facilitating health-related patent search. Our tool, called TWINC, relies on a search engine tuned during several patent retrieval competitions, enhanced with intelligent interaction modules, such as chemical query, normalization and expansion. While the functionality of related article search showed promising performances, the ad hoc search results in fairly contrasted results. Nonetheless, TWINC performed well during the PatOlympics competition and was appreciated by intellectual property experts. This result should be balanced by the limited evaluation sample. We can also assume that it can be customized to be applied in corporate search environments to process domain and company-specific vocabularies, including non-English literature and patents reports.

Loss of the anion exchanger DRA (Slc26a3), or PAT1 (Slc26a6), alters sulfate transport by the distal ileum and overall sulfate homeostasis.

PubMed

Whittamore, Jonathan M; Hatch, Marguerite

2017-09-01

The ileum is considered the primary site of inorganic sulfate ([Formula: see text]) absorption. In the present study, we explored the contributions of the apical chloride/bicarbonate (Cl - /[Formula: see text]) exchangers downregulated in adenoma (DRA; Slc26a3), and putative anion transporter 1 (PAT1; Slc26a6), to the underlying transport mechanism. Transepithelial 35 [Formula: see text] and 36 Cl - fluxes were determined across isolated, short-circuited segments of the distal ileum from wild-type (WT), DRA-knockout (KO), and PAT1-KO mice, together with measurements of urine and plasma sulfate. The WT distal ileum supported net sulfate absorption [197.37 ± 13.61 (SE) nmol·cm -2 ·h -1 ], but neither DRA nor PAT1 directly contributed to the unidirectional mucosal-to-serosal flux ([Formula: see text]), which was sensitive to serosal (but not mucosal) DIDS, dependent on Cl - , and regulated by cAMP. However, the absence of DRA significantly enhanced net sulfate absorption by one-third via a simultaneous rise in [Formula: see text] and a 30% reduction to the secretory serosal-to-mucosal flux ([Formula: see text]). We propose that DRA, together with PAT1, contributes to [Formula: see text] by mediating sulfate efflux across the apical membrane. Associated with increased ileal sulfate absorption in vitro, plasma sulfate was 61% greater, and urinary sulfate excretion ( U SO4 ) 2.2-fold higher, in DRA-KO mice compared with WT controls, whereas U SO4 was increased 1.8-fold in PAT1-KO mice. These alterations to sulfate homeostasis could not be accounted for by any changes to renal sulfate handling suggesting that the source of this additional sulfate was intestinal. In summary, we characterized transepithelial sulfate fluxes across the mouse distal ileum demonstrating that DRA (and to a lesser extent, PAT1) secretes sulfate with significant implications for intestinal sulfate absorption and overall homeostasis. NEW & NOTEWORTHY Sulfate is an essential anion that is actively absorbed from the small intestine involving members of the Slc26 gene family. Here, we show that the main intestinal chloride transporter Slc26a3, known as downregulated in adenoma (DRA), also handles sulfate and contributes to its secretion into the lumen. In the absence of functional DRA (as in the disease congenital chloride diarrhea), net intestinal sulfate absorption was significantly enhanced resulting in substantial alterations to overall sulfate homeostasis. Copyright © 2017 the American Physiological Society.

Hormone signaling linked to silkmoth sex pheromone biosynthesis involves Ca2+/calmodulin-dependent protein kinase II-mediated phosphorylation of the insect PAT family protein Bombyx mori lipid storage droplet protein-1(BmLsd)

USDA-ARS?s Scientific Manuscript database

The structurally-related members of the PAT family of proteins, which are so name based on similarity amongst perilipin, adipophilin/adipocyte differentiation-related protein (ADRP), and tail-interacting protein of 47 kilodaltons (TIP47), are cytoplasmic lipid droplet (LD)-associated proteins charac...

Polymorphic amplified typing sequences (PATS) and pulsed-field gel electrophoresis (PFGE) yield comparable results in the strain typing of a diverse set of bovine Escherichia coli O157 isolates

USDA-ARS?s Scientific Manuscript database

The PCR-based Escherichia coli O157 (O157) strain typing system, Polymorphic Amplified Typing Sequences (PATS), targets insertions-deletions (Indels) and single nucleotide polymorphisms (SNPs) at the XbaI and AvrII(BlnI) restriction enzyme sites, respectively, besides amplifying four known virulenc...

Comparison of noninvasive pulse transit time estimates as markers of blood pressure using invasive pulse transit time measurements as a reference.

PubMed

Gao, Mingwu; Olivier, N Bari; Mukkamala, Ramakrishna

2016-05-01

Pulse transit time (PTT) measured as the time delay between invasive proximal and distal blood pressure (BP) or flow waveforms (invasive PTT [I-PTT]) tightly correlates with BP PTT estimated as the time delay between noninvasive proximal and distal arterial waveforms could therefore permit cuff-less BP monitoring. A popular noninvasive PTT estimate for this application is the time delay between ECG and photoplethysmography (PPG) waveforms (pulse arrival time [PAT]). Another estimate is the time delay between proximal and distal PPG waveforms (PPG-PTT). PAT and PPG-PTT were assessed as markers of BP over a wide physiologic range using I-PTT as a reference. Waveforms for determining I-PTT, PAT, and PPG-PTT through central arteries were measured from swine during baseline conditions and infusions of various hemodynamic drugs. Diastolic, mean, and systolic BP varied widely in each subject (group average (mean ± SE) standard deviation between 25 ± 2 and 36 ± 2 mmHg). I-PTT correlated well with all BP levels (group average R(2) values between 0.86 ± 0.03 and 0.91 ± 0.03). PPG-PTT also correlated well with all BP levels (group average R(2) values between 0.81 ± 0.03 and 0.85 ± 0.02), and its R(2) values were not significantly different from those of I-PTT PAT correlated best with systolic BP (group average R(2) value of 0.70 ± 0.04), but its R(2) values for all BP levels were significantly lower than those of I-PTT (P < 0.005) and PPG-PTT (P < 0.02). The pre-ejection period component of PAT was responsible for its inferior correlation with BP In sum, PPG-PTT was not different from I-PTT and superior to the popular PAT as a marker of BP. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

A photoacoustic imaging reconstruction method based on directional total variation with adaptive directivity.

PubMed

Wang, Jin; Zhang, Chen; Wang, Yuanyuan

2017-05-30

In photoacoustic tomography (PAT), total variation (TV) based iteration algorithm is reported to have a good performance in PAT image reconstruction. However, classical TV based algorithm fails to preserve the edges and texture details of the image because it is not sensitive to the direction of the image. Therefore, it is of great significance to develop a new PAT reconstruction algorithm to effectively solve the drawback of TV. In this paper, a directional total variation with adaptive directivity (DDTV) model-based PAT image reconstruction algorithm, which weightedly sums the image gradients based on the spatially varying directivity pattern of the image is proposed to overcome the shortcomings of TV. The orientation field of the image is adaptively estimated through a gradient-based approach. The image gradients are weighted at every pixel based on both its anisotropic direction and another parameter, which evaluates the estimated orientation field reliability. An efficient algorithm is derived to solve the iteration problem associated with DDTV and possessing directivity of the image adaptively updated for each iteration step. Several texture images with various directivity patterns are chosen as the phantoms for the numerical simulations. The 180-, 90- and 30-view circular scans are conducted. Results obtained show that the DDTV-based PAT reconstructed algorithm outperforms the filtered back-projection method (FBP) and TV algorithms in the quality of reconstructed images with the peak signal-to-noise rations (PSNR) exceeding those of TV and FBP by about 10 and 18 dB, respectively, for all cases. The Shepp-Logan phantom is studied with further discussion of multimode scanning, convergence speed, robustness and universality aspects. In-vitro experiments are performed for both the sparse-view circular scanning and linear scanning. The results further prove the effectiveness of the DDTV, which shows better results than that of the TV with sharper image edges and clearer texture details. Both numerical simulation and in vitro experiments confirm that the DDTV provides a significant quality improvement of PAT reconstructed images for various directivity patterns.

Photon activated therapy (PAT) using monochromatic Synchrotron x-rays and iron oxide nanoparticles in a mouse tumor model: feasibility study of PAT for the treatment of superficial malignancy

PubMed Central

2012-01-01

Background X-rays are known to interact with metallic nanoparticles, producing photoelectric species as radiosensitizing effects, and have been exploited in vivo mainly with gold nanoparticles. The purpose of this study was to investigate the potential of sensitizing effect of iron oxide nanoparticles for photon activated therapy. Methods X-rays photon activated therapy (PAT) was studied by treating CT26 tumor cells and CT26 tumor-bearing mice loaded with 13-nm diameter FeO NP, and irradiating them at 7.1 keV near the Fe K-edge using synchrotron x-rays radiation. Survival of cells was determined by MTT assay, and tumor regression assay was performed for in vivo model experiment. The results of PAT treated groups were compared with x-rays alone control groups. Results A more significant reduction in viability and damage was observed in the FeO NP-treated irradiated cells, compared to the radiation alone group (p < 0.04). Injection of FeO NP (100 mg/kg) 30 min prior to irradiation elevated the tumor concentration of magnetite to 40 μg of Fe/g tissue, with a tumor-to-muscle ratio of 17.4. The group receiving FeO NP and radiation of 10 Gy showed 80% complete tumor regression (CTR) after 15–35 days and relapse-free survival for up to 6 months, compared to the control group, which showed growth retardation, resulting in 80% fatality. The group receiving radiation of 40 Gy showed 100% CTR in all cases irrespective of the presence of FeO NP, but CTR was achieved earlier in the PAT-treated group compared with the radiation alone group. Conclusions An iron oxide nanoparticle enhanced therapeutic effect with relatively low tissue concentration of iron and 10 Gy of monochromatic X-rays. Since 7.1 keV X-rays is attenuated very sharply in the tissue, FeO NP-PAT may have promise as a potent treatment option for superficial malignancies in the skin, like chest wall recurrence of breast cancer. PMID:23111059

In-Flight Technique for Acquiring Mid- And Far-Field Sonic Boom Signatures

NASA Technical Reports Server (NTRS)

Stansbery, Eugene G.; Baize, Daniel G.; Maglieri, Domenic, J.

1999-01-01

Flight test experiments have been conducted to establish the feasibility of obtaining sonic boom signature measurements below a supersonic aircraft using the NASA Portable Automatic Triggering System (PATS) mounted in the USMC Pioneer Unmanned Aerial Vehicle (UAV). This study forms a part of the NASA sonic boom minimization activities, specifically the demonstration of persistence of modified boom signatures to very large distances in a real atmosphere. The basic objective of the measurement effort was to obtain a qualitative view of the sonic boom signature in terms of its shape, number of shocks, their locations, and their relative strength. Results suggest that the technique may very well provide quantitative information relative to mid-field and far-field boom signatures. The purpose of this presentation is to describe the arrangement and operation of this in-flight system and to present the resulting sonic boom measurements. Adaption and modification of two PATS to the UAV payload section are described and include transducer location, mounting arrangement and recording system isolation. Ground static runup, takeoff and landing, and cruise flight checkouts regarding UAV propeller and flow noise on the PATS automated triggering system and recording mode are discussed. For the proof-of-concept tests, the PATS instrumented UAV was flown under radar control in steady-level flight at the altitude of 8700 feet MSL and at a cruise speed of about 60 knots. The USN F-4N sonic boom generating aircraft was vectored over the UAV on reciprocal headings at altitudes of about 1 1,000 feet MSL and 13,000 feet MSL at about Mach 1. 15. Sonic boom signatures were acquired on both PATS for all six supersonic passes. Although the UAV propeller noise is clearly evident in all the measurements, the F-4 boom signature is clearly distinguishable and is typically N-wave in character with sharply rising shock fronts and with a mid-shock associated with the inlet-wing juncture. Consideration is being given to adapting the PATS/TJAV measurements technique to the NASA Learjet to determine feasibility of acquiring in-flight boom signatures in the altitude range of 10,000 feet to 40,000 feet.

Impact of embryo number and periconceptional undernutrition on factors regulating adipogenesis, lipogenesis, and metabolism in adipose tissue in the sheep fetus.

PubMed

Lie, Shervi; Morrison, Janna L; Williams-Wyss, Olivia; Ozanne, Susan E; Zhang, Song; Walker, Simon K; Kleemann, David O; MacLaughlin, Severence M; Roberts, Claire T; McMillen, I Caroline

2013-10-15

Maternal undernutrition around the time of conception is associated with an increased risk of insulin resistance in adulthood. We hypothesized that maternal undernutrition during the periconceptional (PCUN: -60 to 7 days) and/or preimplantation (PIUN: 0-7 days) periods would result in a decrease in UCP1 expression and the abundance of insulin signaling molecules and an increase in the abundance of factors that regulate adipogenesis and lipogenesis in fetal perirenal adipose tissue (PAT) and that these effects would be different in singletons and twins. Maternal PCUN and PIUN resulted in a decrease in UCP1 expression in PAT, and PIUN resulted in higher circulating insulin concentrations, an increased abundance of pPKCζ and PDK4, and a decreased abundance of Akt1, phosphorylated mTOR, and PPARγ in PAT in singleton and twin fetuses. In singletons, there was also a decrease in the abundance of p110β in PAT in the PCUN and PIUN groups and an increase in total AMPKα in PAT in the PIUN group. In twins, however, there was an increase in the abundance of mTOR in the PCUN group and an increase in PDK2 and decrease in total AMPKα in the PIUN group. Thus exposure to periconceptional undernutrition programs changes in the thermogenic capacity and the insulin and fatty acid oxidation signaling pathway in visceral fat, and these effects are different in singletons and twins. These findings are important, as the thermogenic capacity of brown fat and the insulin sensitivity of visceral fat are important determinants of the risk of developing obesity and an insulin resistance phenotype in later life.

Reliability of the Watch-PAT 200 in Detecting Sleep Apnea in Highway Bus Drivers

PubMed Central

Yuceege, Melike; Firat, Hikmet; Demir, Ahmet; Ardic, Sadik

2013-01-01

Objective: To predict the validity of Watch-PAT (WP) device for sleep disordered breathing (SDB) among highway bus drivers. Method: A total number of 90 highway bus drivers have undergone polysomnography (PSG) and Watch-PAT test simultaneously. Routine blood tests and the routine ear-nose-throat (ENT) exams have been done as well. Results: The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 89.1%, 76.9%, 82% and 85.7% for RDI > 15, respectively. WRDI, WODI, W < 90% duration and Wmean SaO2 results were well correlated with the PSG results. In the sensitivity and specificity analysis, when diagnosis of sleep apnea was defined for different cut-off values of RDI of 5, 10 and 15, AUC (95%CI) were found as 0.84 (0.74-0.93), 0.87 (95%CI: 0.79-0.94) and 0.91 (95%CI: 0.85-0.97), respectively. There were no statistically significant differences between Stage1+2/Wlight and Stage REM/WREM. The percentage of Stage 3 sleep had difference significant statistically from the percentage of Wdeep. Total sleep times in PSG and WP showed no statistically important difference. Total NREM duration and total WNREM duration had no difference either. Conclusion: Watch-PAT device is helpful in detecting SDB with RDI > 15 in highway bus drivers, especially in drivers older than 45 years, but has limited value in drivers younger than 45 years old who have less risk for OSA. Therefore, WP can be used in the former group when PSG is not easily available. Citation: Yuceege M; Firat F; Demir A; Ardic S. Reliability of the Watch-PAT 200 in detecting sleep apnea in highway bus drivers. J Clin Sleep Med 2013;9(4):339-344. PMID:23585749

Antioxidative cellular response of lepidopteran ovarian cells to photoactivated alpha-terthienyl.

PubMed

Huang, Qingchun; Yun, Xinming; Rao, Wenbing; Xiao, Ciying

2017-04-01

Photodynamic sensitizers as useful alternative agents have been used for population control against insect pests, and the response of insect ovarian cells towards the photosensitizers is gaining attention because of the next reproduction. In this paper, antioxidative responses of lepidopteran ovarian Tn5B1-4 and Sf-21 cells to photoactivated alpha-terthienyl (PAT) are investigated. PAT shows positive inhibitory cytotoxicity on the two ovarian cells, and its inhibition on cell viability is enhanced as the concentrations are increased and the irradiation time is extended. Median inhibitory concentrations (IC 50 ) are 3.36μg/ml to Tn5B1-4 cells, and 3.15μg/ml to Sf-21 cells at 15min-UV-A irradiation 2h-dark incubation. Under 10.0μg/ml PAT exposure, 15min-UV-A irradiation excites higher ROS production than 5min-UV-A irradiation does in the ovarian cells, the maximum ROS content is about 7.1 times in Tn5B1-4 cells and 4.3 times in Sf-21 cells, and the maximum malondialdehyde levels in Tn5B1-4 and Sf-21 cells are about 1.47- and 1.36-fold higher than the control groups, respectively. Oxidative stress generated by PAT strongly decreases the activities of POD, SOD and CAT, and induces an accumulation of Tn5B1-4 cells in S phase and Sf-21 cells in G2/M phase in a concentration-dependent fashion. Apoptosis accumulation of Tn5B1-4 cells and the persistent post-irradiation cytotoxicity are further observed, indicating different antioxidative tolerance and arrest pattern of the two ovarian cells towards the cytotoxicity of PAT. Copyright © 2016 Elsevier Inc. All rights reserved.

Differential Effects of Bariatric Surgery Versus Exercise on Excessive Visceral Fat Deposits

PubMed Central

Wu, Fu-Zong; Huang, Yi-Luan; Wu, Carol C.; Wang, Yen-Chi; Pan, Hsiang-Ju; Huang, Chin-Kun; Yeh, Lee-Ren; Wu, Ming-Ting

2016-01-01

Abstract The aim of the present study was to compare differential impacts of bariatric surgery and exercise-induced weight loss on excessive abdominal and cardiac fat deposition. Excessive fat accumulation around the heart may play an important role in the pathogenesis of cardiovascular disease. Recent evidences have suggested that bariatric surgery results in relatively less decrease in epicardial fat compared with abdominal visceral fat and paracardial fat. Sixty-four consecutive overweight or obese subjects were enrolled in the study. Clinical characteristics and metabolic profiles were recorded. The volumes of abdominal visceral adipose tissue (AVAT), abdominal subcutaneous adipose tissue (ASAT), epicardial (EAT), and paracardial adipose tissue (PAT) were measured by computed tomography in the bariatric surgery group (N = 25) and the exercise group (N = 39) at baseline and 3 months after intervention. Subjects in both the surgery and exercise groups showed significant reduction in body mass index (15.97%, 7.47%), AVAT (40.52%, 15.24%), ASAT (31.40, 17.34%), PAT (34.40%, 12.05%), and PAT + EAT (22.31%, 17.72%) (all P < 0.001) after intervention compared with baseline. In both the groups, the decrease in EAT was small compared with the other compartments (P < 0.01 in both groups). Compared with the exercise group, the surgery group had greater loss in abdominal and cardiac visceral adipose tissue (AVAT, ASAT, PAT, EAT+PAT) (P < 0.001), but lesser loss in EAT (P = 0.037). Compared with the exercise group, bariatric surgery results in significantly greater percentage loss of excessive fat deposits except for EAT. EAT, but not PAT, was relatively preserved despite weight reduction in both the groups. The physiological impact of persistent EAT deserves further investigation. PMID:26844473

Microvascular endothelial function and cognitive performance: The ELSA-Brasil cohort study.

PubMed

Brant, Luisa; Bos, Daniel; Araujo, Larissa Fortunato; Ikram, M Arfan; Ribeiro, Antonio Lp; Barreto, Sandhi M

2018-06-01

Impaired microvascular endothelial function may be implicated in the etiology of cognitive decline. Yet, current data on this association are inconsistent. Our objective is to investigate the relation of microvascular endothelial function to cognitive performance in the ELSA-Brasil cohort study. A total of 1521 participants from ELSA-Brasil free of dementia underwent peripheral arterial tonometry (PAT) to quantify microvascular endothelial function (PAT-ratio and mean baseline pulse amplitude (BPA)) and cognitive tests that covered the domains of memory, verbal fluency, and executive function at baseline. Cognitive tests in participants aged 55 years old and above were repeated during the second examination (mean follow-up: 3.5 (0.3) years). Linear regression and generalized linear models were used to evaluate the association between endothelial function, global cognitive performance, and performance on specific cognitive domains. In unadjusted cross-sectional analyses, we found that BPA and PAT-ratio were associated with worse global cognitive performance (mean difference for BPA: -0.07, 95% CI: -0.11; -0.03, p<0.01; mean difference for PAT-ratio: 0.11, 95% CI: 0.01; 0.20, p=0.02), worse performance on learning, recall, and word recognition tests (BPA: -0.87, 95% CI: -1.21; -0.52, p<0.01; PAT-ratio: 1.58, 95% CI: 0.80; 2.36, p<0.01), and only BPA was associated with worse performance in verbal fluency tests (-0.70, 95% CI: -1.19; -0.21, p<0.01). Adjustments for age, sex, and level of education rendered the associations statistically non-significant. Longitudinally, there was no association between microvascular endothelial and cognitive functions. The associations between microvascular endothelial function and cognition are explained by age, sex, and educational level. Measures of microvascular endothelial function may be of limited value with regard to preclinical cognitive deficits.

bdhA-patD operon as a virulence determinant, revealed by a novel large-scale approach for identification of Legionella pneumophila mutants defective for amoeba infection.

PubMed

Aurass, P; Pless, B; Rydzewski, K; Holland, G; Bannert, N; Flieger, A

2009-07-01

Legionella pneumophila, the causative agent of Legionnaires' disease, is an intracellular parasite of eukaryotic cells. In the environment, it colonizes amoebae. After being inhaled into the human lung, the bacteria infect and damage alveolar cells in a way that is mechanistically similar to the amoeba infection. Several L. pneumophila traits, among those the Dot/Icm type IVB protein secretion machinery, are essential for exploiting host cells. In our search for novel Legionella virulence factors, we developed an agar plate assay, designated the scatter screen, which allowed screening for mutants deficient in infecting Acanthamoeba castellanii amoebae. Likewise, an L. pneumophila clone bank consisting of 23,000 transposon mutants was investigated here, and 19 different established Legionella virulence genes, for example, dot/icm genes, were identified. Importantly, 70 novel virulence-associated genes were found. One of those is L. pneumophila bdhA, coding for a protein with homology to established 3-hydroxybutyrate dehydrogenases involved in poly-3-hydroxybutyrate metabolism. Our study revealed that bdhA is cotranscribed with patD, encoding a patatin-like protein of L. pneumophila showing phospholipase A and lysophospholipase A activities. In addition to strongly reduced lipolytic activities and increased poly-3-hydroxybutyrate levels, the L. pneumophila bdhA-patD mutant showed a severe replication defect in amoebae and U937 macrophages. Our data suggest that the operon is involved in poly-3-hydroxybutyrate utilization and phospholipolysis and show that the bdhA-patD operon is a virulence determinant of L. pneumophila. In summary, the screen for amoeba-sensitive Legionella clones efficiently isolated mutants that do not grow in amoebae and, in the case of the bdhA-patD mutant, also human cells.

Accelerated high-resolution photoacoustic tomography via compressed sensing

NASA Astrophysics Data System (ADS)

Arridge, Simon; Beard, Paul; Betcke, Marta; Cox, Ben; Huynh, Nam; Lucka, Felix; Ogunlade, Olumide; Zhang, Edward

2016-12-01

Current 3D photoacoustic tomography (PAT) systems offer either high image quality or high frame rates but are not able to deliver high spatial and temporal resolution simultaneously, which limits their ability to image dynamic processes in living tissue (4D PAT). A particular example is the planar Fabry-Pérot (FP) photoacoustic scanner, which yields high-resolution 3D images but takes several minutes to sequentially map the incident photoacoustic field on the 2D sensor plane, point-by-point. However, as the spatio-temporal complexity of many absorbing tissue structures is rather low, the data recorded in such a conventional, regularly sampled fashion is often highly redundant. We demonstrate that combining model-based, variational image reconstruction methods using spatial sparsity constraints with the development of novel PAT acquisition systems capable of sub-sampling the acoustic wave field can dramatically increase the acquisition speed while maintaining a good spatial resolution: first, we describe and model two general spatial sub-sampling schemes. Then, we discuss how to implement them using the FP interferometer and demonstrate the potential of these novel compressed sensing PAT devices through simulated data from a realistic numerical phantom and through measured data from a dynamic experimental phantom as well as from in vivo experiments. Our results show that images with good spatial resolution and contrast can be obtained from highly sub-sampled PAT data if variational image reconstruction techniques that describe the tissues structures with suitable sparsity-constraints are used. In particular, we examine the use of total variation (TV) regularization enhanced by Bregman iterations. These novel reconstruction strategies offer new opportunities to dramatically increase the acquisition speed of photoacoustic scanners that employ point-by-point sequential scanning as well as reducing the channel count of parallelized schemes that use detector arrays.

Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami–Ogata syndrome)

PubMed Central

Kagami, Masayo; Kurosawa, Kenji; Miyazaki, Osamu; Ishino, Fumitoshi; Matsuoka, Kentaro; Ogata, Tsutomu

2015-01-01

Paternal uniparental disomy 14 (UPD(14)pat) and epimutations and microdeletions affecting the maternally derived 14q32.2 imprinted region lead to a unique constellation of clinical features such as facial abnormalities, small bell-shaped thorax with a coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly, and polyhydramnios. In this study, we performed comprehensive clinical studies in patients with UPD(14)pat (n=23), epimutations (n=5), and microdeletions (n=6), and revealed several notable findings. First, a unique facial appearance with full cheeks and a protruding philtrum and distinctive chest roentgenograms with increased coat-hanger angles to the ribs constituted the pathognomonic features from infancy through childhood. Second, birth size was well preserved, with a median birth length of ±0 SD (range, −1.7 to +3.0 SD) and a median birth weight of +2.3 SD (range, +0.1 to +8.8 SD). Third, developmental delay and/or intellectual disability was invariably present, with a median developmental/intellectual quotient of 55 (range, 29–70). Fourth, hepatoblastoma was identified in three infantile patients (8.8%), and histological examination in two patients showed a poorly differentiated embryonal hepatoblastoma with focal macrotrabecular lesions and well-differentiated hepatoblastoma, respectively. These findings suggest the necessity of an adequate support for developmental delay and periodical screening for hepatoblastoma in the affected patients, and some phenotypic overlap between UPD(14)pat and related conditions and Beckwith–Wiedemann syndrome. On the basis of our previous and present studies that have made a significant contribution to the clarification of underlying (epi)genetic factors and the definition of clinical findings, we propose the name ‘Kagami–Ogata syndrome' for UPD(14)pat and related conditions. PMID:25689926

In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages.

PubMed

Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher; Zhang, Qiang; Cobley, Claire M; Gao, Feng; Xia, Younan; Wang, Lihong V

2010-08-24

Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bioconjugated with [Nle(4),D-Phe(7)]-alpha-melanocyte-stimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bioconjugated AuNCs enhanced contrast approximately 300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS).

WE-H-206-03: Promises and Challenges of Benchtop X-Ray Fluorescence CT (XFCT) for Quantitative in Vivo Imaging

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

Cho, S.

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffersmore » from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.« less

WE-H-206-01: Photoacoustic Tomography: Multiscale Imaging From Organelles to Patients by Ultrasonically Beating the Optical Diffusion Limit

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

Wang, L.

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffersmore » from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.« less

WE-H-206-00: Advances in Preclinical Imaging

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

NONE

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffersmore » from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.« less

WE-H-206-02: Recent Advances in Multi-Modality Molecular Imaging of Small Animals

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

Tsui, B.

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffersmore » from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.« less

Decidability of formal theories and hyperincursivity theory

NASA Astrophysics Data System (ADS)

Grappone, Arturo G.

2000-05-01

This paper shows the limits of the Proof Standard Theory (briefly, PST) and gives some ideas of how to build a proof anticipatory theory (briefly, PAT) that has no such limits. Also, this paper considers that Gödel's proof of the undecidability of Principia Mathematica formal theory is not valid for axiomatic theories that use a PAT to build their proofs because the (hyper)incursive functions are self-representable.

Genomic Characterization Reveals Insights Into Patulin Biosynthesis and Pathogenicity in Penicillium Species.

PubMed

Li, Boqiang; Zong, Yuanyuan; Du, Zhenglin; Chen, Yong; Zhang, Zhanquan; Qin, Guozheng; Zhao, Wenming; Tian, Shiping

2015-06-01

Penicillium species are fungal pathogens that infect crop plants worldwide. P. expansum differs from P. italicum and P. digitatum, all major postharvest pathogens of pome and citrus, in that the former is able to produce the mycotoxin patulin and has a broader host range. The molecular basis of host-specificity of fungal pathogens has now become the focus of recent research. The present report provides the whole genome sequence of P. expansum (33.52 Mb) and P. italicum (28.99 Mb) and identifies differences in genome structure, important pathogenic characters, and secondary metabolite (SM) gene clusters in Penicillium species. We identified a total of 55 gene clusters potentially related to secondary metabolism, including a cluster of 15 genes (named PePatA to PePatO), that may be involved in patulin biosynthesis in P. expansum. Functional studies confirmed that PePatL and PePatK play crucial roles in the biosynthesis of patulin and that patulin production is not related to virulence of P. expansum. Collectively, P. expansum contains more pathogenic genes and SM gene clusters, in particular, an intact patulin cluster, than P. italicum or P. digitatum. These findings provide important information relevant to understanding the molecular network of patulin biosynthesis and mechanisms of host-specificity in Penicillium species.

Home sleep study for patients with myasthenia gravis.

PubMed

Yeh, J-H; Lin, C-M; Chiu, H-C; Bai, C-H

2015-09-01

The objective of the study was to examine predictors for sleep-disordered breathing (SDB) in patients with myasthenia gravis (MG) using Watch-PAT. We prospectively studied 58 consecutive patients with MG without respiratory symptoms for a full-night Watch-PAT with concomitant recording of the MG score and acetylcholine receptor antibody concentration and analyzed potential risk factors of SDB. Twenty-four patients (41%) had definitive SDB, which was mild in 12 patients, moderate in six, and severe in six. Assessing risk factors with multivariate models, we found four significant predictors (BMI, age, male gender, and use of azathioprine); BMI was the most powerful predictor. The severity and prevalence of sleep-disordered breathing had no significant association with MG score, myasthenia stage, or seropositivity of acetylcholine receptor antibody. The prevalence of SDB in myasthenic patients with mild and moderate weakness was high when using the Watch-PAT. Both myasthenia-specific factors (use of azathioprine) and general predictors in terms of BMI, age, and male gender predisposed the development of SDB in patients with myasthenia gravis. Careful screening of patients with myasthenia gravis at risk of SDB using Watch-PAT might improve the quality of sleep and cardiovascular health through proper treatment of underlying SDB. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Prospective, Multicenter Study to Compare a Disposable, High-fluid Capacity Underpad to Nonpermeable, Disposable, Reusable Containment Products on Incontinence-associated Dermatitis Rates Among Skilled Nursing Facility Residents.

PubMed

Motta, Glenda; Milne, Catherine T

2017-12-01

Due to the high prevalence of incontinence among skilled nursing facility (SNF) residents, incontinence-associated derma- titis (IAD) is a common occurrence. In addition, facility staff may mistakenly identify IAD as a pressure injury. A prospective, descriptive, multicenter study was conducted in 3 Connecticut facilities to evaluate the effect of substituting a disposable, high- uid capacity underpad for nonpermeable disposable and reusable containment products on the rate of IADs. Residents with and without IAD but with high IAD risk scores who were bed- or chairbound or ambulatory and used disposable nonpermeable briefs and underpads or reusable, laundered containment products when in bed longer than 2 hours were randomly enrolled and observed for a 4-week period. Facility staff were trained on the importance of differentiating between IAD and pressure injury; they substituted the study product (a disposable, high- uid capacity underpad) for all previously used containment products. Patient risk for IAD and skin condition were assessed using the Perineal Assessment Tool (PAT) and the Skin Condition Assessment Tool (SAT), respectively, at 5 time points: baseline, week 1, week 2, week 3, and week 4. The PAT is a 4-item instrument based conceptually on the 4 determinants in perineal skin breakdown; subscales are rated from 1 (least risk) to 3 (most risk), with a total score range of 4 to 12. The SAT is used to evaluate IAD speci cally, generating a cumulative severity score ranging from 0 to 3 on area of skin affected, degree of redness, and depth of ero- sion. Final data analysis was conducted on 40 residents: 25 had IAD present at enrollment and 15 were deemed high risk for developing IAD. Mean SAT scores in the 25 participants with IAD decreased with signi cance at week 1 (P = .0016), week 2 (P = .0023), week 3 (P = .0005), and week 4 (P <.0001). Baseline IAD severity scores averaged 3.3 ± 1.7. Overall IAD average severity scores in this group decreased from baseline mean of 3.3 ± 1.7 to 0.7 ± 1.4 at week 4 (P <.001). The 15 participants with intact, nondamaged skin at enrollment did not develop IAD from baseline to week 4, and PAT score risk levels decreased from high (7 or greater) to low (6 or less) as a result of a speci c reduction in the duration of irritant exposure category for 11 (73%) of this group of participants by week 4. PAT risk level scores for both IAD and non-IAD participants at baseline averaged 8.1 ± 1.4; after 4 weeks, they averaged 7.0 ± 1.5). Although change was not significant, results suggest the use of a disposable, high- uid capacity underpad improved SAT scores over time. IAD rates increased in each facility, but pressure injury incidence rates decreased for the study duration. Replacing a nonpermeable, reusable containment product with a disposable, high- uid capacity underpad when SNF residents are in bed longer than 2 hours may impact the severity of IAD and reduce its incidence. The inverse impact reported on IAD and pressure injury incidence rates 1 month after training suggest study educational efforts had a short-lasting effect. Future research is indicated to determine the most effective method to improve nurses' ability to identify and distinguish IAD from pressure injury in the SNF setting.

Pressure retarded osmosis as a controlling system for traditional renewables

NASA Astrophysics Data System (ADS)

Carravetta, Armando; Fecarotta, Oreste; La Rocca, Michele; Martino, Riccardo

2015-04-01

Pressure retarded osmosis (PRO) is a viable but still not diffused form of renewable energy (see Maisonneuve et al., 2015 for a recent literature review). In PRO, water from a low salinity feed solution permeates through a membrane into a pressurized, high salinity draw solution, giving rise to a positive pressure drop; then energy is obtained by depressurizing the permeate through a hydro-turbine and brackish water is discharged. Many technological, environmental and economical aspects are obstacles in the diffusion of PRO, like the vulnerability of the membranes to fouling, the impact of the brackish water on the local marine environment, the high cost of membranes, etc. We are interested in the use of PRO as a combined form of energy with other renewable energy source like solar, wind or mini hydro in water supply networks (WSN). For the wide diffusion of renewables one of the major concerns of commercial power companies is to obtain very stable form of energy to comply with prescriptions of electricity grid operators and with the instant energy demand curve. Renewables are generally very variable form of energy, for the influence of climatic conditions on available power, and of the fluctuation in water demand in WSN. PRO is a very flexible technology where with appropriate turbines and control system power can be varied continuously to compensate for variation of other source of energy. Therefore, PRO is suitable to be used as a balancing system for commercial power system. We will present a simulation of the performance of a PRO used in combination with three different renewables. In the first two scenarios PRO compensate the difference between energy demand and energy production of a solar power plant and hydro power plant in a WSN. In the third scenario PRO is used to compensate daily variation of energy production in a wind power plant. Standard curves of energy production and energy demand for southern Italy are used. In order to control PRO production an appropriate hydro turbine system is necessary. Therefore, pumps as turbine (PAT) are used in alternative to a classical hydraulic turbine (Carravetta et al., 2013). PAT can be easily regulated by hydraulic system, of by an inverter, granting the necessary flexibility of energy production with a sensible reduction of machinery cost. Maisonneuve J, Pillay P, Laflamme C.B. Pressure-retarded osmotic power system model considering non-ideal effects. Renewable Energy. 2015; 75(3): 416-424. Carravetta A, Del Giudice G, Fecarotta O, Ramos HM. Pump as Turbine (PAT) Design in Water Distribution Network by System Effectiveness. Water. 2013; 5(3):1211-1225.

Non-contact photoacoustic tomography and ultrasonography for tissue imaging

PubMed Central

Rousseau, Guy; Blouin, Alain; Monchalin, Jean-Pierre

2011-01-01

The detection of ultrasound in photoacoustic tomography (PAT) and ultrasonography (US) usually relies on ultrasonic transducers in contact with the biological tissue. This is a major drawback for important potential applications such as surgery and small animal imaging. Here we report the use of remote optical detection, as used in industrial laser-ultrasonics, to detect ultrasound in biological tissues. This strategy enables non-contact implementation of PAT and US without exceeding laser exposure safety limits. The method uses suitably shaped laser pulses and a confocal Fabry-Perot interferometer in differential configuration to reach quantum-limited sensitivity. Endogenous and exogenous inclusions exhibiting optical and acoustic contrasts were detected ex vivo in chicken breast and calf brain specimens. Inclusions down to 0.5 mm in size were detected at depths well exceeding 1 cm. The method could significantly expand the scope of applications of PAT and US in biomedical imaging. PMID:22254164

Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

PubMed Central

Nobel, Yael R.; Cox, Laura M.; Kirigin, Francis F.; Bokulich, Nicholas A.; Yamanishi, Shingo; Teitler, Isabel; Chung, Jennifer; Sohn, Jiho; Barber, Cecily M.; Goldfarb, David S.; Raju, Kartik; Abubucker, Sahar; Zhou, Yanjiao; Ruiz, Victoria E.; Li, Huilin; Mitreva, Makedonka; Alekseyenko, Alexander V.; Weinstock, George M.; Sodergren, Erica; Blaser, Martin J.

2015-01-01

Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment. PMID:26123276

Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment.

PubMed

Nobel, Yael R; Cox, Laura M; Kirigin, Francis F; Bokulich, Nicholas A; Yamanishi, Shingo; Teitler, Isabel; Chung, Jennifer; Sohn, Jiho; Barber, Cecily M; Goldfarb, David S; Raju, Kartik; Abubucker, Sahar; Zhou, Yanjiao; Ruiz, Victoria E; Li, Huilin; Mitreva, Makedonka; Alekseyenko, Alexander V; Weinstock, George M; Sodergren, Erica; Blaser, Martin J

2015-06-30

Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

In vivo molecular photoacoustic tomography of melanomas targeted by bio-conjugated gold nanocages

PubMed Central

Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher; Zhang, Qiang; Cobley, Claire M.; Gao, Feng; Xia, Younan; Wang, Lihong V.

2010-01-01

Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bio-conjugated with [Nle4,D-Phe7]-α-melanocyte-stimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bio-conjugated AuNCs enhanced contrast ~300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS). PMID:20731439

Petrology and Geochemistry of LEW 88663 and PAT 91501: High Petrologic L Chondrites

NASA Astrophysics Data System (ADS)

Mittlefehldt, D. W.; Lindstrom, M. M.; Field, S. W.

1993-07-01

Primitive achondrites (e.g., Acapulco, Lodran) are believed to be highly metamorphosed chondritic materials, perhaps up to the point of anatexis in some types. Low petrologic grade equivalents of these achondrites are unknown, so the petrologic transition from chondritic to achondritic material cannot be documented. However, there are rare L chondrites of petrologic grade 7 that may have experienced igneous processes, and study of these may yield information relevant to the formation of primitive achondrites, and perhaps basaltic achondrites, from chondritic precursors. We have begun the study of the L7 chondrites LEW 88663 and PAT 91501 as part of our broader study of primitive achondrites. Here, we present our preliminary petrologic and geochemical data on these meteorites. Petrology and Mineral Compositions: LEW 88663 is a granular achondrite composed of equant, subhedral to anhedral olivine grains poikilitically enclosed in networks of orthopyroxene and plagioclase. Small grains of clinopyroxene are spatially associated with orthopyroxene. Troilite occurs as large anhedral and small rounded grains. The smaller troilite grains are associated with the orthopyroxene-plagioclase networks. PAT 91501 is a vesicular stone containing centimeter-sized troilite +/- metal nodules. Its texture consists of anhedral to euhedral olivine grains, anhedral orthopyroxene grains (some with euhedral clinopyroxene overgrowths), anhedral to euhedral clinopyroxene, and interstitial plagioclase and SiO2-Al2O3-K2O- rich glass. In some areas, olivine is poikilitically enclosed in orthopyroxene. Fine-grained troilite, metal, and euhedral chromite occur interstitial to the silicates. Average mineral compositions for LEW 88663 are olivine Fo(sub)75.8, orthopyroxene Wo(sub)3.4En(sub)76.2Fs(sub)20.4, clinopyroxene Wo(sub)42.6En(sub)47.8Fs(sub)9.6, plagioclase Ab(sub)75.0An(sub)21.6Or(sub)3.4. Mineral compositions for PAT 91501 are olivine Fo(sub)73.8, orthopyroxene Wo(sub)4.5En(sub)74.8Fs(sub)20.7, clinopyroxene Wo(sub)34.3En(sub)52.4Fs(sub)13.3, plagioclase Ab(sub)81.6An(sub)14.0Or(sub)44. Geochemistry: We have completed INM analysis of LEW 88663 only; analyses of PAT 91501 are in progress. The weighted mean lithophile element (refractory, moderately volatile, and volatile) content of LEW 88663 normalized to average L chondrites [1] is 0.97. The weighted mean siderophile element (excluding Fe) content is only 0.57x L. This supports the suggestion that LEW 88663 lost metal relative to average L chondrites, although not as complete as implied earlier [1]. The mean lithophile-element abundance is that of L chondrites, but the lithophile-element pattern is fractionated. Highly incompatible elements are enriched in LEW 88663 relative to L chondrites (e.g., La 2.6x, Sm 1.9x L chondrites), while the more compatible elements are near L chondrite levels or depleted (e.g., Lu 1.1x, Sc 0.94x, Cr 0.87x L chondrites). Discussion: LEW 88663 and PAT 91501 are texturally similar to the Shaw L7 chondrite [3] and to poikilitic textured clasts in LL chondrites [4]. Several textural and mineralogical characteristics of PAT 91501 indicate that this stone is in part igneous. Large rounded troilite +/- metal nodules imply that melting occurred in the metal-troilite system. Interstitial material consists of euhedral, zoned chromites, euhedral clinopyroxene overgrowths on orthopyroxene, and plagioclase + glass. Olivine often shows euhedral faces in contact with the interstitial regions. These textures indicate that the interstitial regions were molten. The average pyroxene compositions in PAT 91501 indicate equilibration at 1200 degrees C [5], above the ordinary chondrite solidus [6]. Although PAT 91501 is in part igneous in origin, we have yet to determine whether it represents an extension of parent body heating from that of metamorphosed L chondrites, or whether it represents impact melting on the parent body. We will evaluate shock features, cooling rates, and the bulk composition of PAT 91501 in order to investigate this further. Orthopyroxenes in LEW 88663 have a lower Wo content, and clinopyroxenes have a higher Wo content, than those in PAT 91501, and have equilibrated to lower temperatures, perhaps ~1000 degrees C [5]. References: [1] Wasson and Kallemeyn (1988) Phil. Trans. R. Soc. Lond., A325, 535. [2] Davis et al. (1993) LPS XXIV, 375. [3] Taylor et al. (1979) GCA, 43, 323. [4] Fodor and Keil (1975) Meteoritics, 10, 325. [5] Lindsley (1983) Am. Mineral., 68, 477. [6] Jurewicz et al. (1993) LPS XXIV, 739.

Data Exploration Theater 3

NASA Image and Video Library

2017-12-08

The NASA Center for Climate Simulation (NCCS) Data Exploration Theater features a 17- by 6-foot multi-screen visualization wall for engaging visitors and scientists with high-definition movies of simulation results. Here, the wall displays a 3.5-kilometer-resolution global simulation that captures numerous cloud types at groundbreaking fidelity. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

Data Exploration Theater 4

NASA Image and Video Library

2017-12-08

The NASA Center for Climate Simulation (NCCS) Data Exploration Theater features a 17- by 6-foot multi-screen visualization wall for engaging visitors and scientists with high-definition movies of simulation results. Here, the wall displays a 5-kilometer-resolution global simulation that captures numerous cloud types at groundbreaking fidelity. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

Data Exploration Theater 1

NASA Image and Video Library

2017-12-08

The NASA Center for Climate Simulation (NCCS) Data Exploration Theater features a 17- by 6-foot multi-screen visualization wall for engaging visitors and scientists with high-definition movies of simulation results. Here, the wall displays a 3.5-kilometer-resolution global simulation that captures numerous cloud types at groundbreaking fidelity. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

Data Exploration Theater 2

NASA Image and Video Library

2017-12-08

The NASA Center for Climate Simulation (NCCS) Data Exploration Theater features a 17- by 6-foot multi-screen visualization wall for engaging visitors and scientists with high-definition movies of simulation results. Here, the wall displays a 5-kilometer-resolution global simulation that captures numerous cloud types at groundbreaking fidelity. Credit: NASA/Pat Izzo To learn more about NCCS go to: www.nasa.gov/topics/earth/features/climate-sim-center.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

In-line monitoring of granule moisture in fluidized-bed dryers using microwave resonance technology.

PubMed

Buschmüller, Caroline; Wiedey, Wolfgang; Döscher, Claas; Dressler, Jochen; Breitkreutz, Jörg

2008-05-01

This is the first report on in-line moisture measurement of pharmaceutical products by microwave resonance technology. In order to meet the FDA's PAT approach, a microwave resonance sensor appropriate for pharmaceutical use was developed and implemented into two different fluidized-bed dryers. The novel sensor enables a continuous moisture measurement independent from the product density. Hence, for the first time precise real time determination of the moisture in pharmaceutical granules becomes possible. The qualification of the newly developed sensor was performed by drying placebo granules under experimental conditions and the validation using drug loaded granules under real process conditions. The results of the investigations show good correlations between water content of the granules determined by the microwave resonance sensor and both reference methods, loss on drying by infrared light exposure and Karl Fischer titration. Furthermore, a considerable time saving in the drying process was achieved through monitoring the residual water content continuously by microwave resonance technology instead of the formerly used discontinuous methods.

Mutation of the murC and murB Genes Impairs Heterocyst Differentiation in Anabaena sp. Strain PCC 7120

PubMed Central

Videau, Patrick; Rivers, Orion S.; Ushijima, Blake; Oshiro, Reid T.; Kim, Min Joo; Philmus, Benjamin

2016-01-01

ABSTRACT To stabilize cellular integrity in the face of environmental perturbations, most bacteria, including cyanobacteria, synthesize and maintain a strong, flexible, three-dimensional peptidoglycan lattice. Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium capable of differentiating morphologically distinct nitrogen-fixing heterocyst cells in a periodic pattern. While heterocyst development has been shown to require proper peptidoglycan remodeling, the role of peptidoglycan synthesis has remained unclear. Here we report the identification of two peptidoglycan synthesis genes, murC (alr5065) and murB (alr5066), as required for heterocyst development. The murC and murB genes are predicted to encode a UDP-N-acetylmuramate:l-alanine ligase and a UDP-N-acetylenolpyruvoylglucosamine reductase, respectively, and we confirm enzymatic function through complementation of Escherichia coli strains deficient for these enzymes. Cells depleted of either murC or murB expression failed to differentiate heterocysts under normally inducing conditions and displayed decreased filament integrity. To identify the stage(s) of development affected by murC or murB depletion, the spatial distribution of expression of the patterning marker gene, patS, was examined. Whereas murB depletion did not affect the pattern of patS expression, murC depletion led to aberrant expression of patS in all cells of the filament. Finally, expression of gfp controlled by the region of DNA immediately upstream of murC was enriched in differentiating cells and was repressed by the transcription factor NtcA. Collectively, the data in this work provide evidence for a direct link between peptidoglycan synthesis and the maintenance of a biological pattern in a multicellular organism. IMPORTANCE Multicellular organisms that differentiate specialized cells must regulate morphological changes such that both cellular integrity and the dissemination of developmental signals are preserved. Here we show that the multicellular bacterium Anabaena, which differentiates a periodic pattern of specialized heterocyst cells, requires peptidoglycan synthesis by the murine ligase genes murC (alr5065) and murB (alr5066) for maintenance of patterned gene expression, filament integrity, and overall development. This work highlights the significant influence that intracellular structure and intercellular connections can have on the execution of a developmental program. PMID:26811320

Mutation of the murC and murB Genes Impairs Heterocyst Differentiation in Anabaena sp. Strain PCC 7120.

PubMed

Videau, Patrick; Rivers, Orion S; Ushijima, Blake; Oshiro, Reid T; Kim, Min Joo; Philmus, Benjamin; Cozy, Loralyn M

2016-04-01

To stabilize cellular integrity in the face of environmental perturbations, most bacteria, including cyanobacteria, synthesize and maintain a strong, flexible, three-dimensional peptidoglycan lattice. Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium capable of differentiating morphologically distinct nitrogen-fixing heterocyst cells in a periodic pattern. While heterocyst development has been shown to require proper peptidoglycan remodeling, the role of peptidoglycan synthesis has remained unclear. Here we report the identification of two peptidoglycan synthesis genes, murC (alr5065) and murB (alr5066), as required for heterocyst development. The murC and murB genes are predicted to encode a UDP-N-acetylmuramate:L-alanine ligase and a UDP-N-acetylenolpyruvoylglucosamine reductase, respectively, and we confirm enzymatic function through complementation of Escherichia coli strains deficient for these enzymes. Cells depleted of either murC or murB expression failed to differentiate heterocysts under normally inducing conditions and displayed decreased filament integrity. To identify the stage(s) of development affected by murC or murB depletion, the spatial distribution of expression of the patterning marker gene, patS, was examined. Whereas murB depletion did not affect the pattern of patS expression, murC depletion led to aberrant expression of patS in all cells of the filament. Finally, expression of gfp controlled by the region of DNA immediately upstream of murC was enriched in differentiating cells and was repressed by the transcription factor NtcA. Collectively, the data in this work provide evidence for a direct link between peptidoglycan synthesis and the maintenance of a biological pattern in a multicellular organism. Multicellular organisms that differentiate specialized cells must regulate morphological changes such that both cellular integrity and the dissemination of developmental signals are preserved. Here we show that the multicellular bacterium Anabaena, which differentiates a periodic pattern of specialized heterocyst cells, requires peptidoglycan synthesis by the murine ligase genes murC (alr5065) and murB (alr5066) for maintenance of patterned gene expression, filament integrity, and overall development. This work highlights the significant influence that intracellular structure and intercellular connections can have on the execution of a developmental program. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Effects of proposed preflight adaptation training on eye movements, self-motion perception, and motion sickness - A progress report

NASA Technical Reports Server (NTRS)

Parker, D. E.; Reschke, M. F.; Von Gierke, H. E.; Lessard, C. S.

1987-01-01

The preflight adaptation trainer (PAT) was designed to produce rearranged relationships between visual and otolith signals analogous to those experienced in space. Investigations have been undertaken with three prototype trainers. The results indicated that exposure to the PAT sensory rearrangement altered self-motion perception, induced motion sickness, and changed the amplitude and phase of the horizontal eye movements evoked by roll stimulation. However, the changes were inconsistent.

A Bowtie Antenna Coupled Tunable Photon-Assisted Tunneling Double Quantum Well (DQW) THz Detector

DTIC Science & Technology

2002-01-01

Proc. Vol. 692 © 2002 Materials Research Society H4.2 A Bowtie Antenna Coupled Tunable Photon-Assisted Tunneling Double Quantum Well (DQW) THz Detector ...on photon-assisted tunneling (PAT) between the two electron layers in a double quantum well (DQW) heterostructure, will be explained. The detector is...the frequency and strength of that radiation. The THz detector discussed in this paper makes use of photon- assisted tunnelling (PAT) between multiple

Ion Dynamic Capture Experiments With The High Performance Antiproton Trap (HiPAT)

NASA Technical Reports Server (NTRS)

Martin, James; Lewis, Raymond; Chakrabarti, Suman; Sims, William H.; Pearson, J. Boise; Fant, Wallace E.

2002-01-01

To take the first step towards using the energy produced from the matter-antimatter annihilation for propulsion applications, the NASA Marshall Space Flight Center (MSFC) Propulsion Research Center (PRC) has initiated a research activity examining the storage of low energy antiprotons. The High Performance Antiproton Trap (HiPAT) is an electromagnetic system (Penning-Malmberg design) consisting of a 4 Tesla superconductor, a high voltage electrode confinement system, and an ultra high vacuum test section. It has been designed with an ultimate goal of maintaining 10(exp 12) charged particles with a half-life of 18 days. Currently, this system is being evaluated experimentally using normal matter ions that are cheap to produce, relatively easy to handle, and provide a good indication of overall trap behavior (with the exception of assessing annihilation losses). The ions are produced via a positive hydrogen ion source and transported to HiPAT in a beam line equipped with electrostatic optics. The optics serve to both focus and gate the incoming ions, providing microsecond-timed beam pulses that are dynamically captured by cycling the HiPAT forward containment field like a "trap door". Initial dynamic capture experiments have been successfully performed with beam energy and currents set to 1.9 kV and 23 micro-amps, respectively. At these settings up to 2x10(exp 9) ions have been trapped during a single dynamic cycle.

A novel 4-phenyl amino thiourea derivative designed for real-time ratiometric-colorimetric detection of toxic Pb2.

PubMed

Guang, Yi S; Ren, Xia; Zhao, Shuang; Yan, Quan Z; Zhao, Gang; Xu, Yao H

2018-05-12

The objective of this study was to develop a ratiometric and colorimetric organic sensor for Pb 2+ detection in environmental samples. A new probe 4-phenyl amino thiourea (PAT) was designed and synthesized using hydrazine hydrate and phenyl isothiocyanate as raw materials. After its structure was characterized and confirmed, its UV-vis spectral property was investigated in detail. PAT possesses a specifically real-time, ratiometric and colorimetric response to Pb 2+ in dimethyl formamide (DMF)/H 2 O (v/v = 9:1, pH = 7.0) within 18.0 s. There was little interference in the presence of some other common metal ions, such as Fe 3+ , Cd 2+ , Zn 2+ , Mg 2+ , Cr 3+ , Ca 2+ , Ba 2+ , Sn 2+ , Na + , Mn 2+ , Hg 2+ , and Pb 2+ . Under the optimized conditions (DMF/H 2 O with v/v of 9:1, c PAT = 1.0 × 10 -3 mol·L -1 , pH = 7.0), the present sensor PAT was successfully applied for Pb 2+ determination in environmental water samples with satisfied recoveries (83.0%-106.0%) and analytical precision (≤7.2%). The recognition mechanism was confirmed to form a stable 1:1 six-member ring complex between the target dye and Pb 2+ with a coordination constant of 4.96 × 10 4 .

Sinusoidal echo-planar imaging with parallel acquisition technique for reduced acoustic noise in auditory fMRI.

PubMed

Zapp, Jascha; Schmitter, Sebastian; Schad, Lothar R

2012-09-01

To extend the parameter restrictions of a silent echo-planar imaging (sEPI) sequence using sinusoidal readout (RO) gradients, in particular with increased spatial resolution. The sound pressure level (SPL) of the most feasible configurations is compared to conventional EPI having trapezoidal RO gradients. We enhanced the sEPI sequence by integrating a parallel acquisition technique (PAT) on a 3 T magnetic resonance imaging (MRI) system. The SPL was measured for matrix sizes of 64 × 64 and 128 × 128 pixels, without and with PAT (R = 2). The signal-to-noise ratio (SNR) was examined for both sinusoidal and trapezoidal RO gradients. Compared to EPI PAT, the SPL could be reduced by up to 11.1 dB and 5.1 dB for matrix sizes of 64 × 64 and 128 × 128 pixels, respectively. The SNR of sinusoidal RO gradients is lower by a factor of 0.96 on average compared to trapezoidal RO gradients. The sEPI PAT sequence allows for 1) increased resolution, 2) expanded RO frequency range toward lower frequencies, which is in general beneficial for SPL, or 3) shortened TE, TR, and RO train length. At the same time, it generates lower SPL compared to conventional EPI for a wide range of RO frequencies while having the same imaging parameters. Copyright © 2012 Wiley Periodicals, Inc.

Role of amplified spontaneous emission in optical free-space communication links with optical amplification: impact on isolation and data transmission and utilization for pointing, acquisition, and

NASA Astrophysics Data System (ADS)

Winzer, Peter J.; Kalmar, Andras; Leeb, Walter R.

1999-04-01

We investigate the role of amplified spontaneous emission (ASE) produced by an optical booster amplifier at the transmitter of free-space optical communication links. In a communication terminal with a single telescope for both transmission and reception, this ASE power has to be taken into account in connection with transmit-to-receive channel isolation, especially since it partly occupies the same state of polarization and the same frequency band as the receive signal. We show that the booster ASE intercepted by the receiver can represent a non-negligible source of background radiation: In a typical optical intersatellite link scenario, the ASE power spectral density generated by the booster amplifier at the transmitter and coupled to the receiver will be on the order of 10-20 W/Hz, which equals the background radiation of the sun. Exploiting these findings for pointing, acquisition, and tracking (PAT) purposes, we describe a patent-pending PAT system doing without beacon lasers and without the need for diverting a part of the data signal for PAT. Utilizing the transmit booster ASE over a bandwidth of e.g. 20 nm at the receiver, a total power of about -46 dBm is available for PAT purposes without extra power consumption at the transmitter and without the need for beacon lAser alignment.

University of Oklahoma - High Energy Physics

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

Skubic, Patrick L.

2013-07-31

The High Energy Physics program at the University of Oklahoma, Pat Skubic, Principal Investigator, is attempting to understand nature at the deepest level using the most advanced experimental and theoretical tools. The four experimental faculty, Brad Abbott, Phil Gutierrez, Pat Skubic, and Mike Strauss, together with post-doctoral associates and graduate students, are finishing their work as part of the D0 collaboration at Fermilab, and increasingly focusing their investigations at the Large Hadron Collidor (LHC) as part of the ATLAS Collaboration. Work at the LHC has become even more exciting with the recent discovery by ATLAS and the other collaboration, CMS,more » of the long-sought Higgs boson, which plays a key role in generating masses for the elementary constituents of matter. Work of the OUHEP group has been in the three areas of hardware, software, and analysis. Now that the Higgs boson has been discovered, completing the Standard Model of fundamental physics, new efforts will focus on finding hints of physics beyond the standard model, such as supersymmetry. The OUHEP theory group (Kim Milton, PI) also consists of four faculty members, Howie Baer, Chung Kao, Kim Milton, and Yun Wang, and associated students and postdocs. They are involved in understanding fundamental issues in formulating theories of the microworld, and in proposing models that carry us past the Standard Model, which is an incomplete description of nature. They therefore work in close concert with their experimental colleagues. One also can study fundamental physics by looking at the large scale structure of the universe; in particular the ``dark energy'' that seems to be causing the universe to expand at an accelerating rate, effectively makes up about 3/4 of the energy in the universe, and yet is totally unidentified. Dark energy and dark matter, which together account for nearly all of the energy in the universe, are an important probe of fundamental physics at the very shortest distances, or at the very highest energies. The outcomes of the group's combined experimental and theoretical research will be an improved understanding of nature, at the highest energies reachable, from which applications to technological innovation will surely result, as they always have from such studies in the past.« less

Influence of GSTM1 null and low repair XPC PAT+ on anti-B[a]PDE-DNA adduct in mononuclear white blood cells of subjects low exposed to PAHs through smoking and diet.

PubMed

Pavanello, Sofia; Pulliero, Alessandra; Clonfero, Erminio

2008-02-01

The influence of low-activity NER genotypes (XPC PAT-/+, XPA-A23G, XPD Asp312Asn, XPD Lys751Gln) and GSTM1 (active or null) was evaluated on anti-benzo[a]pyrene diol epoxide-(B[a]PDE)-DNA adduct formed in the lymphocyte plus monocyte fraction (LMF). The sample population consisted of 291 healthy subjects with low exposure to polycyclic aromatic hydrocarbons (PAHs) (B[a]P) through their smoking (n=126 smokers) or dietary habits (n=165 non-smokers with high (>or=52 times/year) consumption of charcoaled meat or pizza). The bulky anti-B[a]PDE-DNA adduct levels were detected by HPLC/fluorescence analysis and genotypes by PCR. Anti-B[a]PDE-DNA was present (>or=0.5 adducts/10(8) nucleotides) in 163 (56%) subjects (median (range) 0.77 (0.125-32.0) adducts/10(8) nucleotides), with smokers showing a significantly higher adduct level than non-smokers with high consumption of PAH-rich meals (P<0.01). Our exposed-sample population with unfavourable XPC PAT+/- or +/+ and GSTM1 null genotypes has the significantly highest adduct level (P<0.01). Taking into account tobacco smoke and diet as sources of exposure to B[a]P, low-activity XPC PAT+ shows a major role in smokers (P<0.05) and GSTM1 null in non-smokers with frequent consumption of PAH-rich meals (P<0.01). The modulation of anti-B[a]PDE-DNA adduct in the LMF by GSTM1 null and low-activity XPC PAT+ polymorphisms may be considered as potential genetic susceptibility factors that can modify individual responses to low PAH (B[a]P) genotoxic exposure, with the consequent risk of cancer in the general population.

Measurement of endothelial dysfunction via peripheral arterial tonometry predicts vasculogenic erectile dysfunction

PubMed Central

Kovac, Jason R.; Gomez, Lissette; Smith, Ryan P.; Coward, Robert M.; Gonzales, Marshall A.; Khera, Mohit; Lamb, Dolores J.; Lipshultz, Larry I.

2014-01-01

Introduction Endothelial cell dysfunction is associated with cardiovascular disease and vasculogenic erectile dysfunction (ED). Measured via Peripheral Artery Tonometry (PAT), endothelial dysfunction in the penis is an independent predictor of future cardiovascular events. Aim Determine whether measurement of endothelial dysfunction differentiates men with vasculogenic ED identified by duplex ultrasound from those without. Methods A total of 142 men were retrospectively assessed using patient history, penile duplex ultrasonography (US) and PAT (EndoPAT 2000). ED was self reported and identified on history. Vasculogenic ED was identified in men who exhibited a peak systolic velocity (PSV) of ≤25 cm/s obtained 15 minutes following vasodilator injection. The reactive hyperemia index (RHI), a measurement of endothelial dysfunction in medium/small arteries and the Augmentation Index (AI), a measurement of arterial stiffness, were recorded via PAT. Results Penile duplex US separated men into those with ED (n=111) and without (n=31). The cohort with ED had a PSV of 21±1 cm/s (left cavernous artery) and 22±1 cm/s (Right). The control group without ED had values of 39±2 cm/s (Left) and 39±2 (Right). Given the potential for altered endothelial function in diabetes mellitus, we confirmed that hemoglobin A1c, urinary microalbumin, and vibration pulse threshold were not different in men with vasculogenic ED and those without. RHI in patients with ED (1.85±0.06) was significantly decreased compared to controls (2.15±0.2) (p<0.05). The AI was unchanged when examined in isolation, and when standardized to heart rate. Conclusions Measurement of endothelial function with EndoPAT differentiates men with vasculogenic ED from those without. RHI could be used as a non-invasive surrogate in the assessment of vasculogenic ED and to identify those patients with higher cardiovascular risk. PMID:24784889

Dextran sulfate as a drug delivery platform for drug‐coated balloons: Preparation, characterization, in vitro drug elution, and smooth muscle cell response

PubMed Central

Lamichhane, Sujan; Anderson, Jordan; Remund, Tyler; Kelly, Patrick

2015-01-01

Abstract Drug‐coated balloons (DCBs) have now emerged as a promising approach to treat peripheral artery disease. However, a significant amount of drug from the balloon surface is lost during balloon tracking and results in delivering only a subtherapeutic dose of drug at the diseased site. Hence, in this study, the use of dextran sulfate (DS) polymer was investigated as a platform to control the drug release from balloons. An antiproliferative drug, paclitaxel (PAT), was incorporated into DS films (PAT‐DS). The characterizations using SEM, FT‐IR, and DSC showed that the films prepared were smooth and homogenous with PAT molecularly dispersed in the bulk of DS matrix in amorphous form. An investigation on the interaction of smooth muscle cells (SMCs) with control‐DS and PAT‐DS films showed that both films inhibited SMC growth, with a superior inhibitory effect observed for PAT‐DS films. PAT‐DS coatings were then produced on balloon catheters. The integrity of coatings was well‐maintained when the balloons were either deflated or inflated. In this study, up to 2.2 µg/mm2 of PAT was loaded on the balloons using the DS platform. Drug elution studies showed that only 10 to 20% of the total PAT loaded was released from the PAT‐DS coated balloons during the typical time period of balloon tracking (1 min) and then ∼80% of the total PAT loaded was released during the typical time period of balloon inflation and treatment (from 1 min to 4 min). Thus, this study demonstrated the use of DS as a platform to control drug delivery from balloons. © 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1416–1430, 2016. PMID:26227252

Petrologic and oxygen isotopic study of ALH 85085-like chondrites

NASA Astrophysics Data System (ADS)

Prinz, M.; Weisberg, M. K.; Clayton, R. N.; Mayeda, T. K.; Ebihara, M.

1994-07-01

Four meteorites (PAT 91546, PCA 91328, PCA 91452, PCA 91467) petrologically similar to ALH 85085 chondrite have now been found. Previous studies of ALH 85085 showed it be a new kind of CR-related microchondrule-bearing chondrite, although one called it a sub-chondrite. The purpose of this study is to learn more about ALH 85085-like meteorites and their relationship to CR and CR-related (LEW 85332, Acfer 182, Bencubbin) chondrites. The methods used included petrology, INA bulk chemical analysis (PAT 91546, PCA 91467), and O isotopic analyses of the whole rocks and separated chondrules and dark inclusions (DIs) from PAT 91546. Since microchondrules and fragments are approximately 20 microns it was necessary to analyze composite samples for O; one was of approximately 100 chondrules, and another was of 5 DIs. Petrologically, the four meteorites are similar to ALH 85085, and there is no basis for determining if all of them, or any combinations, are paired. Mineralogically, olivine and pyroxene are highly magnesian FeNi metal generally has 3-10% Ni, and has a positive Ni-Co correlation similar to that in CR and CR-related chondrites. Refractory inclusions are similar in size to the chondrules and have the following assemblages: (1) hibonite-perovskite, (2) melilite-fassaite-forsterite, (3) grossite (Ca-dialuminate)-melilite-perovskite, (4) spinel-melilite, and (5) spinel-pyroxene aggregates. Chemically, INA analyses indicate that PAT 91546 and PCA 91467 are generally similar to ALH 85085. Oxygen isotopic analyses of the four whole-rock compositions fall along the CR mixing line as does ALH 85085; they are also close to LEW 85332, Acfer 182, and Bencubbin. This supports the concept that these are all CR-related chondrites. Even stronger support is found in the compositions of the chondrules and DIs in PAT 91546, which also plot on or near the CR line.

Design and Preliminary Testing of a High Performance Antiproton Trap (HiPAT)

NASA Technical Reports Server (NTRS)

Martin, James; Meyer, Kirby; Kramer, Kevin; Smith, Gerald; Lewis, Raymond; Rodgers, Stephen L. (Technical Monitor)

2000-01-01

Antimatter represents the pinnacle of energy density, offering the potential to enhance current fusion/fission concepts enabling various classes of deep space missions. Current production rates are sufficient to support proof-of-concept evaluation of many key technologies associated with antimatter-derived propulsion. Storage has been identified as a key enabling technology for all antimatter-related operations, and as such is the current focus of this NASA-MSFC effort to design and fabricate a portable device capable of holding up to 10(exp 12) particles. Hardware has been assembled and initial tests are underway to evaluate the trap behavior using electron gun generated, positive hydrogen ions. Ions have been stored for tens of minutes, limited by observed interaction with background gas. Additionally, radio frequency manipulation is being tested to increase lifetime by stabilizing the stored particles, potentially reducing their interaction with background gas, easing requirements on ultimate trap vacuum and precision mechanical alignment.

Solid Biomass Consumption in Households and Greenhouse Gas Emission Reduction in Latvia / CIETĀS Biomasas PATĒRIŅŠ un SILTUMNĪCEFEKTA GĀZU Emisiju SAMAZINĀŠANAS PERSPEKTĪVA Latvijas MĀJSAIMNIECĪBĀS

NASA Astrophysics Data System (ADS)

Kudrenickis, I.; Klavs, G.

2013-12-01

Utilisation of biomass is an important factor in reducing emission of greenhouse gases (GHG); at the same time, high efficiency of biomass combustion technologies is to be ensured to minimise the methane (CH4) emission thus achieving the most efficient reduction in the total GHG emission. The authors analyse the GHG emission breakdown in Latvia among the sectors not included in the EU Emissions Trading Scheme (ETS), and, in the context of emission reduction, evaluate the energy supply in the Latvian household sector, the types of combustion technologies and the used fuels. The trend is considered for the CH4 emission factor during 1990-2010 in the household sector of EU countries, and the numerical index is calculated which illustrates decoupling the consumption of biomass fuel from CH4 emission. To evaluate the perspective of CH4 emission reduction in the Latvian household sector, two scenarios are investigated for efficiency improvement as related to the central heating equipment based on wood fuel. Biomasas izmantošana ir viens no principiālajiem virzieniem siltumnīcefekta gāzu (SEG) emisiju samazināšanā. Maksimāla SEG emisiju samazinājuma panākšanai ir nepieciešams nodrošināt biomasas sadedzināšanas iekārtu augstu efektivitāti, lai minimizētu ar biomasas kurināmā patēriņu saistīto metāna (CH4) emisiju pieaugumu. Autori raksturo Eiropas Savienības (ES) Emisiju kvotu tirdzniecības sistēmas (ETS) un tajā neietilpstošo sektoru (ne-ETS) nozīmi Latvijas SEG emisiju veidošanā, SEG emisiju relatīvo sadalījumu atbilstoši dažādiem ne- ETS sektoriem un SEG emisiju samazināšanas kontekstā analizē Latvijas mājsaimniecību sektora energoapgādi, patērēto kurināmo un izmantotās kurināmā sadedzināšanas tehnoloģijas. Rakstā ir demonstrēta SEG emisiju inventarizācijā pielietotā CH4 emisiju specifiskā faktora mājsaimniecību sektora koksnes kurināmajam skaitlisko vērtību dinamika 1990-2010 gados dažādās ES valstīs. Salīdzinot kurināmā patēriņa un CH4 emisiju apjoma izmaiņas, ir aprēķināts skaitliskais rādītājs, kas raksturo biomasas kurināmā patēriņa un CH4 emisiju "atsaisti" ES valstīs analizējamā laika posmā. Lai kvantitatīvi novērtētu CH4 emisiju samazināšanas perspektīvu Latvijas mājsaimniecību sektorā, autori analizē divus attīstības scenārijus, kas paredz dažādus mājsaimniecību centrālajā apkurē izmantoto koksnes sadedzināšanas iekārtu efektivitātes pieaugumus.

[The Patient Rights Act (PatRG)--part 1: legislative procedure, treatment contract, contracting parties and their obligations to cooperate and inform].

PubMed

Parzeller, Markus; Zedler, Barbara

2013-01-01

The article deals with the new regulations in the German Civil Code (BGB) which came into effect in Germany on 26 Feb 2013 as the Patient Rights Act (PatRG). In Part I, the legislative procedure, the treatment contract and the contracting parties (Section 630a Civil Code), the applicable regulations (Section 630b Civil Code) and the obligations to cooperate and inform (Section 630c Civil Code) are discussed and critically analysed.

STS-105 Crew Interview: Pat Forrester

NASA Technical Reports Server (NTRS)

2001-01-01

STS-105 Mission Specialist Pat Forrester is seen during a prelaunch interview. He answers questions about his inspiration to become an astronaut, his career path, training for the mission, and his role in the mission's activities. He gives details on the mission's goals, which include the transfer of supplies from the Discovery Orbiter to the International Space Station (ISS) and the change-over of the Expedition 2 and Expedition 3 crews (the resident crews of ISS). Forrester discusses the importance of the ISS in the future of human spaceflight.

Citation for presentation of the 2016 Alfred E. Treibs Award to Patrick G. Hatcher

NASA Astrophysics Data System (ADS)

Bianchi, Thomas S.

2017-03-01

I am privileged and honored to introduce Patrick G. Hatcher as the recipient of the 2016 Alfred E. Treibs Award. I have known Pat for almost twenty years, over which time we have shared an interest in biomacromolecules, biodegradation, and the development of analytical methods. Pat is a true chemist at heart and we have all benefited greatly from his insights on the examination of complex macromolecular materials through state-of-the art spectroscopic analyses.

Freeze-drying process monitoring using a cold plasma ionization device.

PubMed

Mayeresse, Y; Veillon, R; Sibille, P H; Nomine, C

2007-01-01

A cold plasma ionization device has been designed to monitor freeze-drying processes in situ by monitoring lyophilization chamber moisture content. This plasma device, which consists of a probe that can be mounted directly on the lyophilization chamber, depends upon the ionization of nitrogen and water molecules using a radiofrequency generator and spectrometric signal collection. The study performed on this probe shows that it is steam sterilizable, simple to integrate, reproducible, and sensitive. The limitations include suitable positioning in the lyophilization chamber, calibration, and signal integration. Sensitivity was evaluated in relation to the quantity of vials and the probe positioning, and correlation with existing methods, such as microbalance, was established. These tests verified signal reproducibility through three freeze-drying cycles. Scaling-up studies demonstrated a similar product signature for the same product using pilot-scale and larger-scale equipment. On an industrial scale, the method efficiently monitored the freeze-drying cycle, but in a larger industrial freeze-dryer the signal was slightly modified. This was mainly due to the positioning of the plasma device, in relation to the vapor flow pathway, which is not necessarily homogeneous within the freeze-drying chamber. The plasma tool is a relevant method for monitoring freeze-drying processes and may in the future allow the verification of current thermodynamic freeze-drying models. This plasma technique may ultimately represent a process analytical technology (PAT) approach for the freeze-drying process.

Evaluation of the Dark-Medium Objective Lens in Counting Asbestos Fibers by Phase-Contrast Microscopy

PubMed Central

Lee, Eun Gyung; Nelson, John H.; Kashon, Michael L.; Harper, Martin

2015-01-01

A Japanese round-robin study revealed that analysts who used a dark-medium (DM) objective lens reported higher fiber counts from American Industrial Hygiene Association (AIHA) Proficiency Analytical Testing (PAT) chrysotile samples than those using a standard objective lens, but the cause of this difference was not investigated at that time. The purpose of this study is to determine any major source of this difference by performing two sets of round-robin studies. For the first round-robin study, 15 AIHA PAT samples (five each of chrysotile and amosite generated by water-suspended method, and five chrysotile generated by aerosolization method) were prepared with relocatable cover slips and examined by nine laboratories. A second round-robin study was then performed with six chrysotile field sample slides by six out of nine laboratories who participated in the first round-robin study. In addition, two phase-shift test slides to check analysts’ visibility and an eight-form diatom test plate to compare resolution between the two objectives were examined. For the AIHA PAT chrysotile reference slides, use of the DM objective resulted in consistently higher fiber counts (1.45 times for all data) than the standard objective (P-value < 0.05), regardless of the filter generation (water-suspension or aerosol) method. For the AIHA PAT amosite reference and chrysotile field sample slides, the fiber counts between the two objectives were not significantly different. No statistically significant differences were observed in the visibility of blocks of the test slides between the two objectives. Also, the DM and standard objectives showed no pattern of differences in viewing the fine lines and/or dots of each species images on the eight-form diatom test plate. Among various potential factors that might affect the analysts’ performance of fiber counts, this study supports the greater contrast caused by the different phase plate absorptions as the main cause of high counts for the AIHA PAT chrysotile slides using the DM objective. The comparison of fiber count ratios (DM/standard) between the AIHA PAT chrysotile samples and chrysotile field samples indicates that there is a fraction of fibers in the PAT samples approaching the theoretical limit of visibility of the phase-contrast microscope with 3-degree phase-shift. These fibers become more clearly visible through the greater contrast from the phase plate absorption of the DM objective. However, as such fibers are not present in field samples, no difference in counts between the two objectives was observed in this study. The DM objective, therefore, could be allowed for routine fiber counting as it will maintain continuity with risk assessments based on earlier phase-contrast microscopy fiber counts from field samples. Published standard methods would need to be modified to allow a higher aperture specification for the objective. PMID:25737333

Assessing the effect of sea-level change and human activities on a major delta on the Pacific coast of northern South America: The Patía River

NASA Astrophysics Data System (ADS)

Restrepo A, Juan D.

2012-05-01

This paper presents the main physical and human-induced stresses that have shaped the recent evolution of the Patía River delta, the largest and best-developed delta on the western margin of South America. During the Holocene, the Patía Delta moved southward and the northern part became an estuarine system characterized by large extensions of mangrove ecosystems. However, a major human-induced water diversion, starting in 1972, diverted the Patía flow to the Sanguianga River, and shifted the active delta plain back to its former Holocene location. This discharge diversion has led to sediment starvation of the southern delta lobe and changed the northern estuarine system into an active delta plain. In addition, coastal areas of the Patía delta subsided as a result of a devastating tsunami in 1979. Morphological changes along the delta coast are evidenced by: (1) coastal retreat along the whole delta front during the period 1986-2001; (2) coastal retreat along the abandoned delta lobe for the period 2001-2008; 56% of the southern delta shoreline is retreating and only 4% of the coast shows signs of accretion; (3) progradation of the northern delta region during the period 2001-2008; the discharge diversion of the Patía River to the Sanquianga has apparently balanced the observed trends in coastal erosion and sea-level rise (5.1 mm yr- 1 for the period 1984-2006, after the 1979 tsunami); (4) formation of transgressive barrier islands with exposed peat soils in the surf zone; and (5) abandonment of former active distributaries in the southern delta plain with associated inlet closure. In the northern delta lobe, major geomorphic changes include: (1) distributary channel accretion by morphological processes such as sedimentation (also in crevasses), overbank flow, increasing width of levees, inter-distributary channel fill, and colonization of pioneer mangrove; (2) freshening conditions in the Sanguianga distributary channel, a hydrologic change that has shifted the upper estuarine region (salinity < 1 psu) downstream; and (3) changes in vegetation succession; approximately 30% of mangrove forests in the current delta apex have been replaced by freshwater vegetation. Overall, the recent evolution of the Patía has been controlled by the interplay of (1) high basin-wide sediment load; (2) low discharge variability (Qmax/Qmin); (3) spatial switch of delta distributaries related to tectonic movements and subsidence; (4) a relative sea-level rise of 5.1 mm yr- 1 after the occurrence of the 1979 tsunami; (5) episodes of sea-level rise associated with the ENSO cycle; and (6) human-induced discharge diversion. The information presented here is valuable evidence for understanding the role of extreme events versus 'normal' conditions in creating and shaping deltas.

Ultrasensitive Single Fluorescence-Labeled Probe-Mediated Single Universal Primer-Multiplex-Droplet Digital Polymerase Chain Reaction for High-Throughput Genetically Modified Organism Screening.

PubMed

Niu, Chenqi; Xu, Yuancong; Zhang, Chao; Zhu, Pengyu; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

2018-05-01

As genetically modified (GM) technology develops and genetically modified organisms (GMOs) become more available, GMOs face increasing regulations and pressure to adhere to strict labeling guidelines. A singleplex detection method cannot perform the high-throughput analysis necessary for optimal GMO detection. Combining the advantages of multiplex detection and droplet digital polymerase chain reaction (ddPCR), a single universal primer-multiplex-ddPCR (SUP-M-ddPCR) strategy was proposed for accurate broad-spectrum screening and quantification. The SUP increases efficiency of the primers in PCR and plays an important role in establishing a high-throughput, multiplex detection method. Emerging ddPCR technology has been used for accurate quantification of nucleic acid molecules without a standard curve. Using maize as a reference point, four heterologous sequences ( 35S, NOS, NPTII, and PAT) were selected to evaluate the feasibility and applicability of this strategy. Surprisingly, these four genes cover more than 93% of the transgenic maize lines and serve as preliminary screening sequences. All screening probes were labeled with FAM fluorescence, which allows the signals from the samples with GMO content and those without to be easily differentiated. This fiveplex screening method is a new development in GMO screening. Utilizing an optimal amplification assay, the specificity, limit of detection (LOD), and limit of quantitation (LOQ) were validated. The LOD and LOQ of this GMO screening method were 0.1% and 0.01%, respectively, with a relative standard deviation (RSD) < 25%. This method could serve as an important tool for the detection of GM maize from different processed, commercially available products. Further, this screening method could be applied to other fields that require reliable and sensitive detection of DNA targets.

High Efficiency, Low Cost Solar Cells Manufactured Using 'Silicon Ink' on Thin Crystalline Silicon Wafers

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

Antoniadis, H.

Reported are the development and demonstration of a 17% efficient 25mm x 25mm crystalline Silicon solar cell and a 16% efficient 125mm x 125mm crystalline Silicon solar cell, both produced by Ink-jet printing Silicon Ink on a thin crystalline Silicon wafer. To achieve these objectives, processing approaches were developed to print the Silicon Ink in a predetermined pattern to form a high efficiency selective emitter, remove the solvents in the Silicon Ink and fuse the deposited particle Silicon films. Additionally, standard solar cell manufacturing equipment with slightly modified processes were used to complete the fabrication of the Silicon Ink highmore » efficiency solar cells. Also reported are the development and demonstration of a 18.5% efficient 125mm x 125mm monocrystalline Silicon cell, and a 17% efficient 125mm x 125mm multicrystalline Silicon cell, by utilizing high throughput Ink-jet and screen printing technologies. To achieve these objectives, Innovalight developed new high throughput processing tools to print and fuse both p and n type particle Silicon Inks in a predetermined pat-tern applied either on the front or the back of the cell. Additionally, a customized Ink-jet and screen printing systems, coupled with customized substrate handling solution, customized printing algorithms, and a customized ink drying process, in combination with a purchased turn-key line, were used to complete the high efficiency solar cells. This development work delivered a process capable of high volume producing 18.5% efficient crystalline Silicon solar cells and enabled the Innovalight to commercialize its technology by the summer of 2010.« less

Focal Point Theory Models for Dissecting Dynamic Duality Problems of Microbial Infections

PubMed Central

Huang, S.-H.; Zhou, W.; Jong, A.

2008-01-01

Extending along the dynamic continuum from conflict to cooperation, microbial infections always involve symbiosis (Sym) and pathogenesis (Pat). There exists a dynamic Sym-Pat duality (DSPD) in microbial infection that is the most fundamental problem in infectomics. DSPD is encoded by the genomes of both the microbes and their hosts. Three focal point (FP) theory-based game models (pure cooperative, dilemma, and pure conflict) are proposed for resolving those problems. Our health is associated with the dynamic interactions of three microbial communities (nonpathogenic microbiota (NP) (Cooperation), conditional pathogens (CP) (Dilemma), and unconditional pathogens (UP) (Conflict)) with the hosts at different health statuses. Sym and Pat can be quantitated by measuring symbiotic index (SI), which is quantitative fitness for the symbiotic partnership, and pathogenic index (PI), which is quantitative damage to the symbiotic partnership, respectively. Symbiotic point (SP), which bears analogy to FP, is a function of SI and PI. SP-converting and specific pathogen-targeting strategies can be used for the rational control of microbial infections. PMID:18350122

Convergent and discriminant validity of measures of parenting efficacy and control.

PubMed

Lovejoy, M C; Verda, M R; Hays, C E

1997-12-01

Examined the convergent and discriminant validity of the Parent Attribution Test (PAT; Bugental, Blue, & Cruzcosa, 1989), the Parental Locus of Control Scale (PLOC; Campis, Lyman, & Prentice-Dunn, 1986), and the Parenting Sense of Competence-Efficacy Scale (PSOC-Efficacy; Johnston & Mash, 1989) in 3 samples of community mothers. In the 1st 2 samples, mothers also completed measures of negative affect and social desirability. In the 3rd sample, the PAT and PSOC-Efficacy scales were administered with measures of adult attachment style and child behavior problems. There was weak support for the convergent validity of the measures. Moreover, the discriminant validity of the measures was not adequately demonstrated. Our results suggest that PLOC and PSOC-Efficacy scores may reflect distress and response style as well as beliefs about parenting. Scores on the PAT, although less influenced by response style and distress, appear to reflect a different dimension of efficacy than that assessed by other self-report measures.

Micromachined silicon parallel acoustic delay lines as time-delayed ultrasound detector array for real-time photoacoustic tomography

NASA Astrophysics Data System (ADS)

Cho, Y.; Chang, C.-C.; Wang, L. V.; Zou, J.

2016-02-01

This paper reports the development of a new 16-channel parallel acoustic delay line (PADL) array for real-time photoacoustic tomography (PAT). The PADLs were directly fabricated from single-crystalline silicon substrates using deep reactive ion etching. Compared with other acoustic delay lines (e.g., optical fibers), the micromachined silicon PADLs offer higher acoustic transmission efficiency, smaller form factor, easier assembly, and mass production capability. To demonstrate its real-time photoacoustic imaging capability, the silicon PADL array was interfaced with one single-element ultrasonic transducer followed by one channel of data acquisition electronics to receive 16 channels of photoacoustic signals simultaneously. A PAT image of an optically-absorbing target embedded in an optically-scattering phantom was reconstructed, which matched well with the actual size of the imaged target. Because the silicon PADL array allows a signal-to-channel reduction ratio of 16:1, it could significantly simplify the design and construction of ultrasonic receivers for real-time PAT.

Determination of patulin in commercial apple juice by micellar electrokinetic chromatography.

PubMed

Murillo, M; González-Peñas, E; Amézqueta, S

2008-01-01

A novel and validated micellar electrokinetic capillary chromatography (MEKC) method using ultraviolet detection (UV) has been applied to the quantitative analysis of patulin (PAT) in commercial apple juice. Patulin was extracted from samples with an ethylacetate solution. The micellar electrokinetic capillary chromatography (MECK) parameters studied for method optimization were buffer composition, voltage, temperature, and a separation between PAT and 5-hydroxymethylfurfural (HMF) (main interference in apple juice PAT analysis) peaks until reaching baseline. The method passes a series of validation tests including selectivity, linearity, limit of detection and quantification (0.7 and 2.5 microgL(-1), respectively), precision (within and between-day variability) and recovery (80.2% RSD=4%), accuracy, and robustness. This method was successfully applied to the measurement of 20 apple juice samples obtained from different supermarkets. One hundred percent of the samples were contaminated with a level greater than the limit of detection, with mean and median values of 41.3 and 35.7 microgL(-1), respectively.

Calibration-free quantification of absolute oxygen saturation based on the dynamics of photoacoustic signals

PubMed Central

Xia, Jun; Danielli, Amos; Liu, Yan; Wang, Lidai; Maslov, Konstantin; Wang, Lihong V.

2014-01-01

Photoacoustic tomography (PAT) is a hybrid imaging technique that has broad preclinical and clinical applications. Based on the photoacoustic effect, PAT directly measures specific optical absorption, which is the product of the tissue-intrinsic optical absorption coefficient and the local optical fluence. Therefore, quantitative PAT, such as absolute oxygen saturation (sO2) quantification, requires knowledge of the local optical fluence, which can be estimated only through invasive measurements or sophisticated modeling of light transportation. In this work, we circumvent this requirement by taking advantage of the dynamics in sO2. The new method works when the sO2 transition can be simultaneously monitored with multiple wavelengths. For each wavelength, the ratio of photoacoustic amplitudes measured at different sO2 states is utilized. Using the ratio cancels the contribution from optical fluence and allows calibration-free quantification of absolute sO2. The new method was validated through both phantom and in vivo experiments. PMID:23903146

Functionalization of gold nanoparticles as antidiabetic nanomaterial

NASA Astrophysics Data System (ADS)

Venkatachalam, M.; Govindaraju, K.; Mohamed Sadiq, A.; Tamilselvan, S.; Ganesh Kumar, V.; Singaravelu, G.

2013-12-01

In the present investigation, functionalization of gold nanoparticles synthesized using propanoic acid 2-(3-acetoxy-4,4,14-trimethylandrost-8-en-17-yl) (PAT) an active biocomponent isolated from Cassia auriculata is studied in detail. On reaction of PAT with aqueous HAuCl4, rapid formation of stable gold nanoparticles was achieved. Formation of gold nanoparticles was confirmed by UV-vis spectroscopy, XRD, GC-MS, FTIR, TEM and SEM with EDAX. Gold nanoparticles mostly were monodisperse, spherical in shape and ranged in size 12-41 nm. Gold nanoparticles synthesised using PAT was administered to alloxan (150 mg/kg body weight) induced diabetic male albino rats at different doses (0.25, 0.5, 0.75 and 1.0 mg/kg body weight) for 28 days. Plasma glucose level, cholesterol and triglyceride were significantly (p < 0.001) reduced in experimental animals treated with gold nanoparticles at dosage of 0.5 mg/kg body weight and plasma insulin increased significantly. The newly genre green gold nanoparticles exhibit remarkable protein tyrosine phosphatase 1B inhibitory activity.

Cuff-less blood pressure measurement using pulse arrival time and a Kalman filter

NASA Astrophysics Data System (ADS)

Zhang, Qiang; Chen, Xianxiang; Fang, Zhen; Xue, Yongjiao; Zhan, Qingyuan; Yang, Ting; Xia, Shanhong

2017-02-01

The present study designs an algorithm to increase the accuracy of continuous blood pressure (BP) estimation. Pulse arrival time (PAT) has been widely used for continuous BP estimation. However, because of motion artifact and physiological activities, PAT-based methods are often troubled with low BP estimation accuracy. This paper used a signal quality modified Kalman filter to track blood pressure changes. A Kalman filter guarantees that BP estimation value is optimal in the sense of minimizing the mean square error. We propose a joint signal quality indice to adjust the measurement noise covariance, pushing the Kalman filter to weigh more heavily on measurements from cleaner data. Twenty 2 h physiological data segments selected from the MIMIC II database were used to evaluate the performance. Compared with straightforward use of the PAT-based linear regression model, the proposed model achieved higher measurement accuracy. Due to low computation complexity, the proposed algorithm can be easily transplanted into wearable sensor devices.

PAT-1 safety analysis report addendum.

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

Weiner, Ruth F.; Schmale, David T.; Kalan, Robert J.

2010-09-01

The Plutonium Air Transportable Package, Model PAT-1, is certified under Title 10, Code of Federal Regulations Part 71 by the U.S. Nuclear Regulatory Commission (NRC) per Certificate of Compliance (CoC) USA/0361B(U)F-96 (currently Revision 9). The purpose of this SAR Addendum is to incorporate plutonium (Pu) metal as a new payload for the PAT-1 package. The Pu metal is packed in an inner container (designated the T-Ampoule) that replaces the PC-1 inner container. The documentation and results from analysis contained in this addendum demonstrate that the replacement of the PC-1 and associated packaging material with the T-Ampoule and associated packaging withmore » the addition of the plutonium metal content are not significant with respect to the design, operating characteristics, or safe performance of the containment system and prevention of criticality when the package is subjected to the tests specified in 10 CFR 71.71, 71.73 and 71.74.« less

Non-invasive monitoring of pulmonary artery pressure from timing information by EIT: experimental evaluation during induced hypoxia.

PubMed

Proença, Martin; Braun, Fabian; Solà, Josep; Adler, Andy; Lemay, Mathieu; Thiran, Jean-Philippe; Rimoldi, Stefano F

2016-06-01

Monitoring of pulmonary artery pressure (PAP) in pulmonary hypertensive patients is currently limited to invasive solutions. We investigate a novel non-invasive approach for continuous monitoring of PAP, based on electrical impedance tomography (EIT), a safe, low-cost and non-invasive imaging technology. EIT recordings were performed in three healthy subjects undergoing hypoxia-induced PAP variations. The pulmonary pulse arrival time (PAT), a timing parameter physiologically linked to the PAP, was automatically calculated from the EIT signals. Values were compared to systolic PAP values from Doppler echocardiography, and yielded strong correlation scores ([Formula: see text]) for all three subjects. Results suggest the feasibility of non-invasive, unsupervised monitoring of PAP.

Weighing Scale-Based Pulse Transit Time is a Superior Marker of Blood Pressure than Conventional Pulse Arrival Time

NASA Astrophysics Data System (ADS)

Martin, Stephanie L.-O.; Carek, Andrew M.; Kim, Chang-Sei; Ashouri, Hazar; Inan, Omer T.; Hahn, Jin-Oh; Mukkamala, Ramakrishna

2016-12-01

Pulse transit time (PTT) is being widely pursued for cuff-less blood pressure (BP) monitoring. Most efforts have employed the time delay between ECG and finger photoplethysmography (PPG) waveforms as a convenient surrogate of PTT. However, these conventional pulse arrival time (PAT) measurements include the pre-ejection period (PEP) and the time delay through small, muscular arteries and may thus be an unreliable marker of BP. We assessed a bathroom weighing scale-like system for convenient measurement of ballistocardiography and foot PPG waveforms - and thus PTT through larger, more elastic arteries - in terms of its ability to improve tracking of BP in individual subjects. We measured “scale PTT”, conventional PAT, and cuff BP in humans during interventions that increased BP but changed PEP and smooth muscle contraction differently. Scale PTT tracked the diastolic BP changes well, with correlation coefficient of -0.80 ± 0.02 (mean ± SE) and root-mean-squared-error of 7.6 ± 0.5 mmHg after a best-case calibration. Conventional PAT was significantly inferior in tracking these changes, with correlation coefficient of -0.60 ± 0.04 and root-mean-squared-error of 14.6 ± 1.5 mmHg (p < 0.05). Scale PTT also tracked the systolic BP changes better than conventional PAT but not to an acceptable level. With further development, scale PTT may permit reliable, convenient measurement of BP.

Impact of metformin treatment and swimming exercise on visfatin levels in high-fat-induced obesity rats.

PubMed

Gao, Ya; Wang, Changjiang; Pan, Tianrong; Luo, Li

2014-02-01

Visfatin is a recently discovered adipocytokine that contributes to glucose and obesity-related conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unknown. We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats. Sprague-Dawley rats were fed a normal diet or a high-fat diet for 16 weeks to develop obesity model. The high-fat-induced obesity model rats were then randomized to metformin (MET), swimming exercise (SWI), or adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat obesity control group and a normal control group, all with 10 rats per group. Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT and SM were determined by Western Blot. Metformin and swimming exercise improved lipid profile, and increased insulin sensitivity and body weight reduction were observed. Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM. Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity.

Weighing Scale-Based Pulse Transit Time is a Superior Marker of Blood Pressure than Conventional Pulse Arrival Time.

PubMed

Martin, Stephanie L-O; Carek, Andrew M; Kim, Chang-Sei; Ashouri, Hazar; Inan, Omer T; Hahn, Jin-Oh; Mukkamala, Ramakrishna

2016-12-15

Pulse transit time (PTT) is being widely pursued for cuff-less blood pressure (BP) monitoring. Most efforts have employed the time delay between ECG and finger photoplethysmography (PPG) waveforms as a convenient surrogate of PTT. However, these conventional pulse arrival time (PAT) measurements include the pre-ejection period (PEP) and the time delay through small, muscular arteries and may thus be an unreliable marker of BP. We assessed a bathroom weighing scale-like system for convenient measurement of ballistocardiography and foot PPG waveforms - and thus PTT through larger, more elastic arteries - in terms of its ability to improve tracking of BP in individual subjects. We measured "scale PTT", conventional PAT, and cuff BP in humans during interventions that increased BP but changed PEP and smooth muscle contraction differently. Scale PTT tracked the diastolic BP changes well, with correlation coefficient of -0.80 ± 0.02 (mean ± SE) and root-mean-squared-error of 7.6 ± 0.5 mmHg after a best-case calibration. Conventional PAT was significantly inferior in tracking these changes, with correlation coefficient of -0.60 ± 0.04 and root-mean-squared-error of 14.6 ± 1.5 mmHg (p < 0.05). Scale PTT also tracked the systolic BP changes better than conventional PAT but not to an acceptable level. With further development, scale PTT may permit reliable, convenient measurement of BP.

A method for aircraft afterburner combustion without flameholders

NASA Astrophysics Data System (ADS)

Birmaher, Shai

2009-12-01

State of the art aircraft afterburners employ spray bars to inject fuel and flameholders to stabilize the combustion process. Such afterburner designs significantly increase the length (and thus weight), pressure losses, and observability of the engine. This thesis presents a feasibility study of a compact 'prime and trigger' (PAT) afterburner concept that eliminates the fuel spray bars and flameholders and, thus, eliminates the above-mentioned problems. In this concept, afterburner fuel is injected just upstream or in between the turbine stages. As the fuel travels through the turbine stages, it evaporates, mixes with the bulk flow, and undergoes some chemical reactions without any significant heat release, a process referred to as 'priming'. Downstream of the turbine stages, combustion could take place through autoignition. However, if fuel autoignition does not occur or if autoignition does not produce a combustion zone that is stable and highly efficient, then a low power pilot, or 'trigger', can be used to control the combustion process. The envisioned trigger for the PAT concept is a jet of product gas from ultra-rich hydrocarbon/air combustion that is injected through the afterburner liner. This 'partial oxidation' (POx) gas, which consists mostly of H2, CO, and diluents, rapidly produces radicals and heat that accelerate the autoignition of the primed mixture and, thus, provide an anchor point for the afterburner combustion process. The objective of this research was to demonstrate the feasibility of the PAT concept by showing that (1) combustion of fuel injected within or upstream of turbine stages can occur only downstream of the turbine stages, and (2) the combustion zone is compact, stable and efficient. This was accomplished using two experimental facilities, a developed theoretical model, and Chemkin simulations. The first facility, termed the Afterburner Facility (AF), simulated the bulk flow temperature, velocity and O2 content through a turbojet combustor, turbine stage and afterburner. To model the PAT concept, Jet-A was injected upstream of the simulated turbine stage and a H2 jet was used to trigger the primed Jet-A combustion process downstream of the turbine stage. H2 was used because POx gas was not available for experiments. The second facility, termed the Propane Autoignition Combustor (PAC), was essentially a scaled-down, simplified version of the AF. The PAC experiments focused on the trigger stage of the PAT concept, using H 2 in lieu of POx gas and employing measurement techniques that were in some ways more detailed than in the AF experiments. The developed model simulated the physics of fuel priming in the AF and predicted the Jet-A autoignition location. It was used to predict and interpret the AF results and to study the feasibility of the PAT concept at pressures outside the AF operating range. Finally, the Chemkin simulations were used to examine the effect of several POx gas compositions on the Jet-A/vitiated-air autoignition process; to compare the POx and H2 triggers; and to explore several reasons for why POx gas and H2 are suitable trigger mechanisms. he experimental, theoretical, and numerical results obtained in this investigation indicated that the PAT concept provides a feasible approach to afterburner combustion. The experiments in the AF showed that the ignition delay of Jet-A is sufficiently long to allow fuel injection within turbine stages without significant heat release upstream of the afterburner. In the AF experiments without the H2 trigger, Jet-A combustion was achieved through autoignition; however, the autoignition combustion zone exhibited large axial fluctuations and low combustion efficiency. The H2 trigger was able to shift the combustion zone upstream, make it more compact, reduce fluctuations in its axial position, and raise the combustion efficiency to nearly 100%. The PAC experiments also showed that a H2 trigger can shift the combustion zone upstream, make it more compact, and increase the combustion efficiency. The PAC results were obtained with lower O 2 content and higher equivalence ratios than in the AF. Therefore, the combined AF and PAC results suggested that the PAT concept is feasible over a wide range of operating conditions. The developed model showed good agreement with the AF results. It also predicted that the PAT concept is feasible at bulk flow pressures outside the AF operating range. Finally, the Chemkin results showed that both the H2 and POx gas triggers can significantly reduce the ignition delay time of primed Jet-A/vitiated air mixtures. Thus, POx gas is a suitable trigger for the PAT concept and should be tested in future experimental investigations.

Unpacking Pat Parker: Intersections and Revolutions in "Movement in Black".

PubMed

Washburn, Amy

2015-01-01

This article explores Pat Parker's poem "Movement in Black." It examines the ways in which she emblematizes intersectionality and simultaneity as forms of revolution in struggles of self and society. It begins with a theoretical and historical apparatus to contextualize Parker as an artist and activist. Then it offers a literary analysis of the poem, focusing on themes of time and space, marginalization and movement, difference and power, visibility and invisibility, and history and memory. It argues that Parker uses autobiographical writing to fuse personal and political sites of resistance.

NASA Aviation Safety Program Systems Analysis/Program Assessment Metrics Review

NASA Technical Reports Server (NTRS)

Louis, Garrick E.; Anderson, Katherine; Ahmad, Tisan; Bouabid, Ali; Siriwardana, Maya; Guilbaud, Patrick

2003-01-01

The goal of this project is to evaluate the metrics and processes used by NASA's Aviation Safety Program in assessing technologies that contribute to NASA's aviation safety goals. There were three objectives for reaching this goal. First, NASA's main objectives for aviation safety were documented and their consistency was checked against the main objectives of the Aviation Safety Program. Next, the metrics used for technology investment by the Program Assessment function of AvSP were evaluated. Finally, other metrics that could be used by the Program Assessment Team (PAT) were identified and evaluated. This investigation revealed that the objectives are in fact consistent across organizational levels at NASA and with the FAA. Some of the major issues discussed in this study which should be further investigated, are the removal of the Cost and Return-on-Investment metrics, the lack of the metrics to measure the balance of investment and technology, the interdependencies between some of the metric risk driver categories, and the conflict between 'fatal accident rate' and 'accident rate' in the language of the Aviation Safety goal as stated in different sources.

NeuroSeek dual-color image processing infrared focal plane array

NASA Astrophysics Data System (ADS)

McCarley, Paul L.; Massie, Mark A.; Baxter, Christopher R.; Huynh, Buu L.

1998-09-01

Several technologies have been developed in recent years to advance the state of the art of IR sensor systems including dual color affordable focal planes, on-focal plane array biologically inspired image and signal processing techniques and spectral sensing techniques. Pacific Advanced Technology (PAT) and the Air Force Research Lab Munitions Directorate have developed a system which incorporates the best of these capabilities into a single device. The 'NeuroSeek' device integrates these technologies into an IR focal plane array (FPA) which combines multicolor Midwave IR/Longwave IR radiometric response with on-focal plane 'smart' neuromorphic analog image processing. The readout and processing integrated circuit very large scale integration chip which was developed under this effort will be hybridized to a dual color detector array to produce the NeuroSeek FPA, which will have the capability to fuse multiple pixel-based sensor inputs directly on the focal plane. Great advantages are afforded by application of massively parallel processing algorithms to image data in the analog domain; the high speed and low power consumption of this device mimic operations performed in the human retina.

'Fast cast' and 'needle Tenotomy' protocols with the Ponseti method to improve clubfoot management in Bangladesh.

PubMed

Evans, Angela; Chowdhury, Mamun; Rana, Sohel; Rahman, Shariar; Mahboob, Abu Hena

2017-01-01

The management of congenital talipes equino varus ( clubfoot deformity ) has been transformed in the last 20 years as surgical correction has been replaced by the non-surgical Ponseti method. The Ponseti method, consists of corrective serial casting followed by maintenance bracing, and has been repeatedly demonstrated to give best results - regarded as the 'gold standard' treatment for paediatric clubfoot. To develop the study protocol Level 2 evidence was used to modify the corrective casting phase of the Ponseti method in children aged up to 12 months. Using Level 4 evidence, the percutaneous Achilles tenotomy (PAT) was performed using a 19-gauge needle instead of a scalpel blade, a technique found to reduce bleeding and scarring. A total of 123 children participated in this study; 88 male, 35 female. Both feet were affected in 67 cases, left only in 22 cases, right only in 34 cases. Typical clubfeet were found in 112/123 cases, six atypical, five syndromic. The average age at first cast was 51 days (13-240 days).The average number of casts applied was five (2-10 casts). The average number of days between the first cast and brace was 37.8 days (10-122 days), including 21 days in a post-PAT cast. Hence, average time of corrective casts was 17 days.Parents preferred the reduced casting time, and were less concerned about unseen skin wounds.PAT was performed in 103/123 cases, using the needle technique. All post tenotomy casts were in situ for three weeks. Minor complications occurred in seven cases - four cases had skin lesions, three cases disrupted casting phase. At another site, 452 PAT were performed using the needle technique. The 'fast cast' protocol Ponseti casting was successfully used in infants aged less than 8 months. Extended manual manipulation of two minutes was the essential modification. Parents preferred the faster treatment phase, and ability to closer observe the foot and skin. The treating physiotherapists preferred the 'fast cast' protocol, achieving better correction with less complication. The needle technique for PAT is a further improvement for the Ponseti method.

EARLY IMPACT MELTING AND SPACE EXPOSURE HISTORY OF THE PAT91501 LCHONDRITE

NASA Technical Reports Server (NTRS)

Bogard, Donald D.; Garrison, D. H.; Herzog, G. F.; Xue, S.; Klein, J.; Middleton, R.

2004-01-01

Collisions probably occurred frequently in the early history of the asteroid belt. Their effects, which should be recorded in meteorites, must have included heating and melting along with shock alteration of mineral textures. Some non-chondritic meteorite types e.g., eucrites and IIE and IAB irons - do indeed give evidence of extensive impact heating more than 3.4 Gyr ago. The ordinary chondrites, in contrast, show little evidence of early impact heating. The Ar-Ar and Rb-Sr ages of ordinary chondrites that experienced intense shock are for the most part relatively young, many less than 1.5 Gyr. The numerous L-chondrites with Ar- Ar ages clustering near 0.5 Gy are a well-known example. One of them, the 105-kg Chico Lchondrite, shows the effects of unusually intense heating. It is approximately 60% impact melt and likely formed as a dyke beneath a large crater when the L-chondrite parent body underwent a very large impact approximately 0.5 Gyr ago. In rare instances, older shock dates are indicated for ordinary chondrites. Dixon et al show early impact resetting of Ar-Ar ages of a few LL-chondrites including MIL 99301 at 4.23 0.03 Gyr, but in none of these stones did shock lead to extensive melting. As of 2003, searches for chondritic melts attributable to early shock had turned up only the Shaw L-chondrite, which has an Ar-Ar age of approximately 4.42 Gyr. PAT91501 is an 8.55-kg L-chondrite containing vesicles and metal-troilite nodules. It is a unique, near-total impact melt, unshocked, depleted in siderophile and chalcophile elements, and contains only approximately 10% relic chondritic material. The authors conclude that PAT91501 crystallized rapidly and from a much more homogeneous melt than did Shaw. They suggest that PAT resembles Chico and likely formed as an impact melt vein within an impact crater. To define the history of PAT, we have determined its Ar-39-Ar-40 age and measured several radioactive and stable nuclides produced during its space exposure to cosmic rays.

Assessing interactions of binary mixtures of Penicillium mycotoxins (PMs) by using a bovine macrophage cell line (BoMacs)

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

Oh, Se-Young, E-mail: ohs@uoguelph.ca

Penicillium mycotoxins (PMs) are toxic contaminants commonly found as mixtures in animal feed. Therefore, it is important to investigate potential joint toxicity of PM mixtures. In the present study, we assessed the joint effect of binary combinations of the following PMs: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA) and penicillic acid (PA) using independent action (IA) and concentration addition (CA) concepts. Previously published toxicity data (i.e. IC25; PM concentration that inhibited bovine macrophage (BoMacs) proliferation by 25%) were initially analyzed, and both concepts agreed that OTA + PA demonstrated synergism (p < 0.05), while PAT + PAmore » showed antagonism (p < 0.05). When a follow-up dilution study was carried out using binary combinations of PMs at three different dilution levels (i.e. IC25, 0.5 ∗ IC25, 0.25 ∗ IC25), only the mixture of CIT + OTA at 0.5 ∗ IC25 was determined to have synergism by both IA and CA concepts with Model Deviation Ratios (MDRs; the ratio of predicted versus observed effect concentrations) of 1.4 and 1.7, respectively. The joint effect of OTA + MPA, OTA + PA and CIT + PAT complied with the IA concept, while CIT + PA, PAT + MPA and PAT + PA were better predicted with the CA over the IA concept. The present study suggests to test both IA and CA concepts using multiple doses when assessing risk of mycotoxin mixtures if the mode of action is unknown. In addition, the study showed that the tested PMs could be predicted by IA or CA within an approximate two-fold certainty, raising the possibility for a joint risk assessment of mycotoxins in food and feed. - Highlights: • We investigated the potential joint toxicity of Penicillium mycotoxin (PM) mixtures. • Independent action (IA) and concentration addition (CA) concepts were used. • 7 out of 10 mixtures followed joint toxicity described by IA or CA concepts. • Both concepts agreed that CIT + OTA mixture had synergistic interaction.« less

Ballistocardiogram as Proximal Timing Reference for Pulse Transit Time Measurement: Potential for Cuffless Blood Pressure Monitoring

PubMed Central

Kim, Chang-Sei; Carek, Andrew M.; Mukkamala, Ramakrishna; Inan, Omer T.; Hahn, Jin-Oh

2015-01-01

Goal We tested the hypothesis that the ballistocardiogram (BCG) waveform could yield a viable proximal timing reference for measuring pulse transit time (PTT). Methods From fifteen healthy volunteers, we measured PTT as the time interval between BCG and a non-invasively measured finger blood pressure (BP) waveform. To evaluate the efficacy of the BCG-based PTT in estimating BP, we likewise measured pulse arrival time (PAT) using the electrocardiogram (ECG) as proximal timing reference and compared their correlations to BP. Results BCG-based PTT was correlated with BP reasonably well: the mean correlation coefficient (r) was 0.62 for diastolic (DP), 0.65 for mean (MP) and 0.66 for systolic (SP) pressures when the intersecting tangent method was used as distal timing reference. Comparing four distal timing references (intersecting tangent, maximum second derivative, diastolic minimum and systolic maximum), PTT exhibited the best correlation with BP when the systolic maximum method was used (mean r value was 0.66 for DP, 0.67 for MP and 0.70 for SP). PTT was more strongly correlated with DP than PAT regardless of the distal timing reference: mean r value was 0.62 versus 0.51 (p=0.07) for intersecting tangent, 0.54 versus 0.49 (p=0.17) for maximum second derivative, 0.58 versus 0.52 (p=0.37) for diastolic minimum, and 0.66 versus 0.60 (p=0.10) for systolic maximum methods. The difference between PTT and PAT in estimating DP was significant (p=0.01) when the r values associated with all the distal timing references were compared altogether. However, PAT appeared to outperform PTT in estimating SP (p=0.31 when the r values associated with all the distal timing references were compared altogether). Conclusion We conclude that BCG is an adequate proximal timing reference in deriving PTT, and that BCG-based PTT may be superior to ECG-based PAT in estimating DP. Significance PTT with BCG as proximal timing reference has potential to enable convenient and ubiquitous cuffless BP monitoring. PMID:26054058

The impact of prism adaptation test on surgical outcomes in patients with primary exotropia.

PubMed

Kiyak Yilmaz, Ayse; Kose, Suheyla; Guven Yilmaz, Suzan; Uretmen, Onder

2015-05-01

We aimed to determine the impact of the preoperative prism adaptation test (PAT) on surgical outcomes in patients with primary exotropia. Thirty-eight consecutive patients with primary exotropia were enrolled. Pre-operative PAT was performed in 18 randomly selected patients (Group 1). Surgery was based on the angle of deviation at distance measured after PAT. The remaining 20 patients in whom PAT was not performed comprised Group 2. Surgery was based on the angle of deviation at distance in these patients. Surgical success was defined as ocular alignment within eight prism dioptres (PD) of orthophoria. Satisfactory motor alignment (± 8 PD) was achieved in 16 Group 1 patients (88.9 per cent) and 16 Group 2 patients (80 per cent) one year after surgery (p = 0.6; chi-square test). There were no statistically significant differences in demographic parameters, pre-operative and post-operative angle of deviation between the two groups (p > 0.05; Mann-Whitney U and chi-square tests). Nine patients in Group 1 (50 per cent) and two patients in Group 2 (10 per cent) had increased binocular vision one year post-operatively. A statistically significant difference was determined in terms of change in binocular single vision between the two groups (p = 0.01; chi-square test). Although the prism adaptation test did not lead to a significant increment in motor success, it may be helpful in achieving a more favourable functional surgical outcome in patients with primary exotropia. © 2014 The Authors. Clinical and Experimental Optometry © 2014 Optometrists Association Australia.

Deep-tissue temperature mapping by multi-illumination photoacoustic tomography aided by a diffusion optical model: a numerical study

NASA Astrophysics Data System (ADS)

Zhou, Yuan; Tang, Eric; Luo, Jianwen; Yao, Junjie

2018-01-01

Temperature mapping during thermotherapy can help precisely control the heating process, both temporally and spatially, to efficiently kill the tumor cells and prevent the healthy tissues from heating damage. Photoacoustic tomography (PAT) has been used for noninvasive temperature mapping with high sensitivity, based on the linear correlation between the tissue's Grüneisen parameter and temperature. However, limited by the tissue's unknown optical properties and thus the optical fluence at depths beyond the optical diffusion limit, the reported PAT thermometry usually takes a ratiometric measurement at different temperatures and thus cannot provide absolute measurements. Moreover, ratiometric measurement over time at different temperatures has to assume that the tissue's optical properties do not change with temperatures, which is usually not valid due to the temperature-induced hemodynamic changes. We propose an optical-diffusion-model-enhanced PAT temperature mapping that can obtain the absolute temperature distribution in deep tissue, without the need of multiple measurements at different temperatures. Based on the initial acoustic pressure reconstructed from multi-illumination photoacoustic signals, both the local optical fluence and the optical parameters including absorption and scattering coefficients are first estimated by the optical-diffusion model, then the temperature distribution is obtained from the reconstructed Grüneisen parameters. We have developed a mathematic model for the multi-illumination PAT of absolute temperatures, and our two-dimensional numerical simulations have shown the feasibility of this new method. The proposed absolute temperature mapping method may set the technical foundation for better temperature control in deep tissue in thermotherapy.

Not all glucocorticoid-induced obesity is the same: differences in adiposity among various diagnostic groups of Cushing syndrome.

PubMed

London, E; Lodish, M; Keil, M; Lyssikatos, C; de la Luz Sierra, M; Nesterova, M; Stratakis, C A

2014-11-01

The cAMP signaling pathway is implicated in bilateral adrenocortical hyperplasias (BAHs), which are often associated with ACTH-independent Cushing syndrome (CS). Although CS is invariably associated with obesity and is frequently associated with PKA signaling defects, we recently reported that its different forms appear to also present with variable weight gain and adiposity. The present study was aimed at characterizing further the phenotypic and molecular differences in periadrenal adipose tissue (PAT) among patients with subtypes of CS, by anthropometric/biochemical analyses and quantification of PKA expression and activity in BAHs in comparison to a non-CS group with aldosterone producing adenomas (APAs). Glucocorticoid levels, serum parameters, and BMI were analyzed among a larger patient cohort including those with different forms of CS, APAs, and Cushing disease. Abdominal CT scans were available for a small subset of patients examined for fat distribution. PAT collected during adrenalectomy was assayed for PKA activity, cAMP, and PKA expression. BMI and BMI z-score were lower in adults with PPNAD with PRKAR1A mutations and in pediatric patients with PPNAD with and without PRKAR1A mutations, respectively. Patients with PPNAD had higher cAMP levels in PAT and different fat distribution. Thus, PKA activity in PAT differed between CS diagnostic groups. Increased cAMP and PKA activity may have contributed to phenotypic differences among subtypes of CS. In agreement with the known roles of cAMP signaling in the regulation of adiposity, patients with PPNAD were less obese than other patients with CS. © Georg Thieme Verlag KG Stuttgart · New York.

Diagnostic Laparoscopy for Trauma: How Not to Miss Injuries.

PubMed

Koto, Modise Z; Matsevych, Oleh Y; Aldous, Colleen

2018-05-01

Diagnostic laparoscopy (DL) is a well-accepted approach for penetrating abdominal trauma (PAT). However, the steps of procedure and the systematic laparoscopic examination are not clearly defined in the literature. The aim of this study was to clarify the definition of DL in trauma surgery by auditing DL performed for PAT at our institution, and to describe the strategies on how to avoid missed injuries. The data of patients managed with laparoscopy for PAT from January 2012 to December 2015 were retrospectively analyzed. The details of operative technique and strategies on how to avoid missed injuries were discussed. Out of 250 patients managed with laparoscopy for PAT, 113 (45%) patients underwent DL. Stab wounds sustained 94 (83%) patients. The penetration of the peritoneal cavity or retroperitoneum was documented in 67 (59%) of patients. Organ evisceration was present in 21 (19%) patients. Multiple injuries were present in 22% of cases. The chest was the most common associated injury. Two (1.8%) iatrogenic injuries were recorded. The conversion rate was 1.7% (2/115). The mean length of hospital stay was 4 days. There were no missed injuries. In the therapeutic laparoscopy (TL) group, DL was performed as the initial part and identified all injuries. There were no missed injuries in the TL group. The predetermined sequential steps of DL and the standard systematic examination of intraabdominal organs were described. DL is a feasible and safe procedure. It accurately identifies intraabdominal injuries. The selected use of preoperative imaging, adherence to the predetermined steps of procedure and the standard systematic laparoscopic examination will minimize the rate of missed injuries.

Simulation of photoacoustic tomography (PAT) system in COMSOL and comparison of two popular reconstruction techniques

NASA Astrophysics Data System (ADS)

Sowmiya, C.; Thittai, Arun K.

2017-03-01

Photoacoustic imaging is a molecular cum functional imaging modality based on differential optical absorption of the incident laser pulse by the endogeneous tissue chromophores. Several numerical simulations and finite element models have been developed in the past to describe and study Photoacoustic (PA) signal generation principles and study the effect of variation in PA parameters. Most of these simulation work concentrate on analyzing extracted 1D PA signals and each of them mostly describe only few of the building blocks of a Photoacoustic Tomography (PAT) imaging system. Papers describing simulation of the entire PAT system in one simulation platform, along with reconstruction is seemingly rare. This study attempts to describe how a commercially available Finite Element software (COMSOL(R)), can serve as a single platform for simulating PAT that couples the electromagnetic, thermodynamic and acoustic pressure physics involved in PA phenomena. Further, an array of detector elements placed at the boundary in the FE model can provide acoustic pressure data that can be exported to Matlab(R) to perform tomographic image reconstruction. The performance of two most commonly used image reconstruction techniques; namely, Filtered Backprojection (FBP) and Synthetic Aperture (SA) beamforming are compared. Results obtained showed that the lateral resolution obtained using FBP vs. SA largely depends on the aperture parameters. FBP reconstruction was able to provide a slightly better lateral resolution for smaller aperture while SA worked better for larger aperture. This interesting effect is currently being investigated further. Computationally FBP was faster, but it had artifacts along the spherical shell on which the data is projected.

Reliability of the Watch-PAT 200 in detecting sleep apnea in highway bus drivers.

PubMed

Yuceege, Melike; Firat, Hikmet; Demir, Ahmet; Ardic, Sadik

2013-04-15

To predict the validity of Watch-PAT (WP) device for sleep disordered breathing (SDB) among highway bus drivers. A total number of 90 highway bus drivers have undergone polysomnography (PSG) and Watch-PAT test simultaneously. Routine blood tests and the routine ear-nose-throat (ENT) exams have been done as well. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 89.1%, 76.9%, 82% and 85.7% for RDI > 15, respectively. WRDI, WODI, W < 90% duration and Wmean SaO2 results were well correlated with the PSG results. In the sensitivity and specificity analysis, when diagnosis of sleep apnea was defined for different cut-off values of RDI of 5, 10 and 15, AUC (95%CI) were found as 0.84 (0.74-0.93), 0.87 (95%CI: 0.79-0.94) and 0.91 (95%CI: 0.85-0.97), respectively. There were no statistically significant differences between Stage1+2/Wlight and Stage REM/WREM. The percentage of Stage 3 sleep had difference significant statistically from the percentage of Wdeep. Total sleep times in PSG and WP showed no statistically important difference. Total NREM duration and total WNREM duration had no difference either. Watch-PAT device is helpful in detecting SDB with RDI > 15 in highway bus drivers, especially in drivers older than 45 years, but has limited value in drivers younger than 45 years old who have less risk for OSA. Therefore, WP can be used in the former group when PSG is not easily available.

Weighing Scale-Based Pulse Transit Time is a Superior Marker of Blood Pressure than Conventional Pulse Arrival Time

PubMed Central

Martin, Stephanie L.-O.; Carek, Andrew M.; Kim, Chang-Sei; Ashouri, Hazar; Inan, Omer T.; Hahn, Jin-Oh; Mukkamala, Ramakrishna

2016-01-01

Pulse transit time (PTT) is being widely pursued for cuff-less blood pressure (BP) monitoring. Most efforts have employed the time delay between ECG and finger photoplethysmography (PPG) waveforms as a convenient surrogate of PTT. However, these conventional pulse arrival time (PAT) measurements include the pre-ejection period (PEP) and the time delay through small, muscular arteries and may thus be an unreliable marker of BP. We assessed a bathroom weighing scale-like system for convenient measurement of ballistocardiography and foot PPG waveforms – and thus PTT through larger, more elastic arteries – in terms of its ability to improve tracking of BP in individual subjects. We measured “scale PTT”, conventional PAT, and cuff BP in humans during interventions that increased BP but changed PEP and smooth muscle contraction differently. Scale PTT tracked the diastolic BP changes well, with correlation coefficient of −0.80 ± 0.02 (mean ± SE) and root-mean-squared-error of 7.6 ± 0.5 mmHg after a best-case calibration. Conventional PAT was significantly inferior in tracking these changes, with correlation coefficient of −0.60 ± 0.04 and root-mean-squared-error of 14.6 ± 1.5 mmHg (p < 0.05). Scale PTT also tracked the systolic BP changes better than conventional PAT but not to an acceptable level. With further development, scale PTT may permit reliable, convenient measurement of BP. PMID:27976741

Comparison of two assays for detection of antibodies against canine parvovirus and canine distemper virus in dogs admitted to a Florida animal shelter.

PubMed

Gray, Lauren K; Crawford, P Cynda; Levy, Julie K; Dubovi, Edward J

2012-05-01

To compare 2 assays for use in the identification of dogs with a protective antibody titer (PAT) against canine parvovirus (CPV) and canine distemper virus (CDV). Prospective cross-sectional study. 431 dogs admitted to a municipal animal shelter in north central Florida. Blood samples were collected from dogs on the day of admission to the shelter. Serum was obtained, criterion-referenced assays were used to identify dogs that had PATs against CPV (titers ≥ 80; hemagglutination inhibition assay) and CDV (titers ≥ 32; virus neutralization assay), and results were compared with results of a semiquantitative ELISA and an immunofluorescence assay (IFA). For correct identification of dogs that had PATs against viruses, the ELISA had significantly higher specificity for CPV (98%) and CDV (95%) than did the IFA (82% and 70%, respectively) and had significantly lower sensitivity for CDV (88%) than did the IFA (97%); the sensitivity for CPV was similar (ELISA, 98%; IFA, 97%). Overall diagnostic accuracy was significantly greater with the ELISA than with the IFA. Predictive value of a positive result for PATs was significantly higher with the ELISA for CPV (99%) and CDV (93%) than with the IFA (92% and 71%, respectively). The ELISA had fewer false-positive results than did the IFA and could be performed on-site in shelters in < 1 hour. Accuracy and practicality of the ELISA may be useful for identifying the infection risk of dogs exposed during outbreaks attributable to CPV and CDV infections in shelters.

Sparse-view photoacoustic tomography using virtual parallel-projections and spatially adaptive filtering

NASA Astrophysics Data System (ADS)

Wang, Yihan; Lu, Tong; Wan, Wenbo; Liu, Lingling; Zhang, Songhe; Li, Jiao; Zhao, Huijuan; Gao, Feng

2018-02-01

To fully realize the potential of photoacoustic tomography (PAT) in preclinical and clinical applications, rapid measurements and robust reconstructions are needed. Sparse-view measurements have been adopted effectively to accelerate the data acquisition. However, since the reconstruction from the sparse-view sampling data is challenging, both of the effective measurement and the appropriate reconstruction should be taken into account. In this study, we present an iterative sparse-view PAT reconstruction scheme where a virtual parallel-projection concept matching for the proposed measurement condition is introduced to help to achieve the "compressive sensing" procedure of the reconstruction, and meanwhile the spatially adaptive filtering fully considering the a priori information of the mutually similar blocks existing in natural images is introduced to effectively recover the partial unknown coefficients in the transformed domain. Therefore, the sparse-view PAT images can be reconstructed with higher quality compared with the results obtained by the universal back-projection (UBP) algorithm in the same sparse-view cases. The proposed approach has been validated by simulation experiments, which exhibits desirable performances in image fidelity even from a small number of measuring positions.

Beam-Plasma Interaction Experiments on the Princeton Advanced Test Stand

NASA Astrophysics Data System (ADS)

Stepanov, A.; Gilson, E. P.; Grisham, L.; Kaganovich, I. D.; Davidson, R. C.

2011-10-01

The Princeton Advanced Test Stand (PATS) is a compact experimental facility for studying the fundamental physics of intense beam-plasma interactions relevant to the Neutralized Drift Compression Experiment - II (NDCX-II). The PATS facility consists of a 100 keV ion beam source mounted on a six-foot-long vacuum chamber with numerous ports for diagnostic access. A 100 keV Ar+ beam is launched into a volumetric plasma, which is produced by a ferroelectric plasma source (FEPS). Beam diagnostics upstream and downstream of the FEPS allow for detailed studies of the effects that the plasma has on the beam. This setup is designed for studying the dependence of charge and current neutralization and beam emittance growth on the beam and plasma parameters. This work reports initial measurements of beam quality produced by the extraction electrodes that were recently installed on the PATS device. The transverse beam phase space is measured with double-slit emittance scanners, and the experimental results are compared to WARP simulations of the extraction system. This research is supported by the U.S. Department of Energy.

Non-invasive Photoacoustic and Fluorescence Sentinel Lymph Node Identification using Dye-loaded Perfluorocarbon Nanoparticles

PubMed Central

Akers, Walter J.; Kim, Chulhong; Berezin, Mikhail; Guo, Kevin; Fuhrhop, Ralph; Lanza, Gregory M.; Fischer, Georg M.; Daltrozzo, Ewald; Zumbusch, Andreas; Cai, Xin; Wang, Lihong V.; Achilefu, Samuel

2010-01-01

The contrast mechanisms used for photoacoustic tomography (PAT) and fluorescence imaging differ in subtle but significant ways. Design of contrast agents for each or both modalities requires an understanding of the spectral characteristics as well as intra- and intermolecular interactions that occur during formulation. We found that fluorescence quenching that occurs in the formulation of near infrared (NIR) fluorescent dyes in nanoparticles results in enhanced contrast for PAT. The ability of the new PAT method to utilize strongly absorbing chromophores for signal generation allowed us to convert a highly fluorescent dye into an exceptionally high PA contrast material. Spectroscopic characterization of the developed NIR dye-loaded perfluorocarbon-based nanoparticles for combined fluorescence and PA imaging revealed distinct dye-dependent photophysical behavior. We demonstrate that the enhanced contrast allows detection of regional lymph nodes of rats in vivo with time-domain optical and photoacoustic imaging methods. The results further show that the use of fluorescence lifetime (FLT) imaging, which is less dependent on fluorescence intensity, provides a strategic approach to bridge the disparate contrast reporting mechanisms of fluorescence and PA imaging methods. PMID:21171567

Simplified solution for osculating Keplerian parameter corrections of GEO satellites for intersatellite optical link

NASA Astrophysics Data System (ADS)

Yılmaz, Umit C.; Cavdar, Ismail H.

2015-04-01

In intersatellite optical communication, the Pointing, Acquisition and Tracking (PAT) phase is one of the important phases that needs to be completed successfully before initiating communication. In this paper, we focused on correcting the possible errors on the Geostationary Earth Orbit (GEO) by using azimuth and elevation errors between Low Earth Orbit (LEO) to GEO optical link during the PAT phase. To minimise the PAT duration, a simplified correction of longitude and inclination errors of the GEO satellite's osculating Keplerian parameters has been suggested. A simulation has been done considering the beaconless tracking and spiral-scanning technique. As a result, starting from the second day, we are able to reduce the uncertainty cone of the GEO satellite by about 200 μrad, if the values are larger than that quantity. The first day of the LEO-GEO links have been used to determine the parameters. Thanks to the corrections, the locking time onto the GEO satellite has been reduced, and more data are able to transmit to the GEO satellite.

Relationships among stallion fertility and semen traits using estimated breeding values of German Warmblood stallions.

PubMed

Gottschalk, Maren; Sieme, Harald; Martinsson, Gunilla; Distl, Ottmar

2017-02-01

A high quality of stallion semen is of particular importance for maximum reproductive efficiency. In the present study, we estimated the relationships among estimated breeding values (EBVs) of semen traits and EBVs for the paternal component of the pregnancy rate per estrus cycle (EBV-PAT) for 100 German Warmblood stallions using correlation and general linear model analyses. The most highly correlated sperm quality trait was total number of progressively motile sperm (r = 0.36). EBV-PAT was considered in three classes with stallions 1 SD below (<80), around (80-120), and above (>120) the population mean of 100. The general linear model analysis showed significant effects for EBVs of all semen traits. EBVs of sperm quality traits greater than 100 to 110 were indicative for EBV-PAT greater than 120. Recommendations for breeding soundness examinations on the basis of the assessments of sperm quality traits and estimation of breeding values seem to be an option to support breeders to improve stallion fertility in the present and future stallion generation. Copyright © 2016 Elsevier Inc. All rights reserved.

The Killer Will Remain Free: On Pat Parker and the Poetics of Madness.

PubMed

Ali, Kazim

2015-01-01

Poet and scholar Kazim Ali reads Pat Parker's Movement in Black intimately, one poet to another, uncovering the shadow-fact of the lives of most people of color: not only the anger that is somehow sublimated into every part of our lives but also the issue that carrying this feeling around has on our mental health itself-that "anger" and "madness" might have sources in one another. Ali concludes that Parker offers a brutal and clear-eyed and ultimately hopeful assessment of the conditions that were faced at the time, and even now, by communities of color.

Acquisition and analysis of primate physiologic data for the Space Shuttle

NASA Astrophysics Data System (ADS)

Eberhart, Russell C.; Hogrefe, Arthur F.; Radford, Wade E.; Sanders, Kermit H.; Dobbins, Roy W.

1988-03-01

This paper describes the design and prototypes of the Physiologic Acquisition and Telemetry System (PATS), which is a multichannel system, designed for large primates, for the data acquisition, telemetry, storage, and analysis of physiological data. PATS is expected to acquire data from units implanted in the abdominal cavities of rhesus monkeys that will be flown aboard the Spacelab. The system will telemeter both stored and real-time internal physiologic measurements to an external Flight Support Station (FSS) computer system. The implanted Data Acquition and Telemetry Subsystem subunit will be externally activated, controlled and reprogrammed from the FSS.

Noninvasively measuring oxygen saturation of human finger-joint vessels by multi-transducer functional photoacoustic tomography

NASA Astrophysics Data System (ADS)

Deng, Zijian; Li, Changhui

2016-06-01

Imaging small blood vessels and measuring their functional information in finger joint are still challenges for clinical imaging modalities. In this study, we developed a multi-transducer functional photoacoustic tomography (PAT) system and successfully imaged human finger-joint vessels from ˜1 mm to <0.2 mm in diameter. In addition, the oxygen saturation (SO2) values of these vessels were also measured. Our results demonstrate that PAT can provide both anatomical and functional information of individual finger-joint vessels with different sizes, which might help the study of finger-joint diseases, such as rheumatoid arthritis.

Ultrasound-Mediated Biophotonic Imaging: A Review of Acousto-Optical Tomography and Photo-Acoustic Tomography

PubMed Central

Wang, Lihong V.

2004-01-01

This article reviews two types of ultrasound-mediated biophotonic imaging–acousto-optical tomography (AOT, also called ultrasound-modulated optical tomography) and photo-acoustic tomography (PAT, also called opto-acoustic or thermo-acoustic tomography)–both of which are based on non-ionizing optical and ultrasonic waves. The goal of these technologies is to combine the contrast advantage of the optical properties and the resolution advantage of ultrasound. In these two technologies, the imaging contrast is based primarily on the optical properties of biological tissues, and the imaging resolution is based primarily on the ultrasonic waves that either are provided externally or produced internally, within the biological tissues. In fact, ultrasonic mediation overcomes both the resolution disadvantage of pure optical imaging in thick tissues and the contrast and speckle disadvantages of pure ultrasonic imaging. In our discussion of AOT, the relationship between modulation depth and acoustic amplitude is clarified. Potential clinical applications of ultrasound-mediated biophotonic imaging include early cancer detection, functional imaging, and molecular imaging. PMID:15096709

'Televaluation' of clinical information systems: an integrative approach to assessing Web-based systems.

PubMed

Kushniruk, A W; Patel, C; Patel, V L; Cimino, J J

2001-04-01

The World Wide Web provides an unprecedented opportunity for widespread access to health-care applications by both patients and providers. The development of new methods for assessing the effectiveness and usability of these systems is becoming a critical issue. This paper describes the distance evaluation (i.e. 'televaluation') of emerging Web-based information technologies. In health informatics evaluation, there is a need for application of new ideas and methods from the fields of cognitive science and usability engineering. A framework is presented for conducting evaluations of health-care information technologies that integrates a number of methods, ranging from deployment of on-line questionnaires (and Web-based forms) to remote video-based usability testing of user interactions with clinical information systems. Examples illustrating application of these techniques are presented for the assessment of a patient clinical information system (PatCIS), as well as an evaluation of use of Web-based clinical guidelines. Issues in designing, prototyping and iteratively refining evaluation components are discussed, along with description of a 'virtual' usability laboratory.

Fast freeze-drying cycle design and optimization using a PAT based on the measurement of product temperature.

PubMed

Bosca, Serena; Barresi, Antonello A; Fissore, Davide

2013-10-01

This paper is focused on the use of an innovative Process Analytical Technology for the fast design and optimization of freeze-drying cycles for pharmaceuticals. The tool is based on a soft-sensor, a device that uses the experimental measure of product temperature during freeze-drying, a mathematical model of the process, and the Extended Kalman Filter algorithm to estimate the sublimation flux, the residual amount of ice in the vial, and some model parameters (heat and mass transfer coefficients). The accuracy of the estimations provided by the soft-sensor has been shown using as test case aqueous solutions containing different excipients (sucrose, polyvinylpyrrolidone), processed at various operating conditions, pointing out that the soft-sensor allows a fast estimation of model parameters and product dynamics without involving expensive hardware or time consuming analysis. The possibility of using the soft-sensor to calculate in-line (or off-line) the design space of the primary drying phase is here presented and discussed. Results evidences that by this way, it is possible to identify the values of the heating fluid temperature that maintain product temperature below the limit value, as well as the operating conditions that maximize the sublimation flux. Various experiments have been carried out to test the effectiveness of the proposed approach for a fast design of the cycle, evidencing that drying time can be significantly reduced, without impairing product quality. Copyright © 2013 Elsevier B.V. All rights reserved.

PDA survey of quality risk management practices in the pharmaceutical, devices, & biotechnology industries.

PubMed

Ahmed, Ruhi; Baseman, Harold; Ferreira, Jorge; Genova, Thomas; Harclerode, William; Hartman, Jeffery; Kim, Samuel; Londeree, Nanette; Long, Michael; Miele, William; Ramjit, Timothy; Raschiatore, Marlene; Tomonto, Charles

2008-01-01

In July 2006 the Parenteral Drug Association's Risk Management Task Force for Aseptic Processes, conducted an electronic survey of PDA members to determine current industry practices regarding implementation of Quality Risk Management in their organizations. This electronic survey was open and publicly available via the PDA website and targeted professionals in our industry who are involved in initiating, implementing, or reviewing risk management programs or decisions in their organizations. One hundred twenty-nine members participated and their demographics are presented in the sidebar "Correspondents Profile". Among the major findings are: *The "Aseptic Processing/Filling" operation is the functional area identified as having the greatest need for risk assessment and quality risk management. *The most widely used methodology in industry to identify risk is Failure Mode and Effects Analysis (FMEA). This tool was most widely applied in assessing change control and for adverse event, complaint, or failure investigations. *Despite the fact that personnel training was identified as the strategy most used for controlling/minimizing risk, the largest contributors to sterility failure in operations are still "Personnel". *Most companies still rely on "Manufacturing Controls" to mitigate risk and deemed the utilization of Process Analytical Technology (PAT) least important in this aspect. *A majority of correspondents verified that they did not periodically assess their risk management programs. *A majority of the correspondents desired to see case studies or examples of risk analysis implementation (as applicable to aseptic processing) in future PDA technical reports on risk management.

Predicting final product properties of melt extruded solid dispersions from process parameters using Raman spectrometry.

PubMed

Vigh, Tamás; Drávavölgyi, Gábor; Sóti, Péter L; Pataki, Hajnalka; Igricz, Tamás; Wagner, István; Vajna, Balázs; Madarász, János; Marosi, György; Nagy, Zsombor K

2014-09-01

Raman spectrometry was utilized to estimate degraded drug percentage, residual drug crystallinity and glass-transition temperature in the case of melt-extruded pharmaceutical products. Tight correlation was shown between the results obtained by confocal Raman mapping and transmission Raman spectrometry, a PAT-compatible potential in-line analytical tool. Immediate-release spironolactone-Eudragit E solid dispersions were the model system, owing to the achievable amorphization and the heat-sensitivity of the drug compound. The deep investigation of the relationship between process parameters, residual drug crystallinity and degradation was performed using statistical tools and a factorial experimental design defining 54 different circumstances for the preparation of solid dispersions. From the examined factors, drug content (10, 20 and 30%), temperature (110, 130 and 150°C) and residence time (2.75, 11.00 and 24.75min) were found to have significant and considerable effect. By forming physically stable homogeneous dispersions, the originally very slow dissolution of the lipophilic and poorly water-soluble spironolactone was reasonably improved, making 3minute release possible in acidic medium. Copyright © 2014 Elsevier B.V. All rights reserved.

A stent for co-delivering paclitaxel and nitric oxide from abluminal and luminal surfaces: Preparation, surface characterization, and in vitro drug release studies

NASA Astrophysics Data System (ADS)

Gallo, Annemarie; Mani, Gopinath

2013-08-01

Most drug-eluting stents currently available are coated with anti-proliferative drugs on both abluminal (toward blood vessel wall) and luminal (toward lumen) surfaces to prevent neointimal hyperplasia. While the abluminal delivery of anti-proliferative drugs is useful for controlling neointimal hyperplasia, the luminal delivery of such drugs impairs or prevents endothelialization which causes late stent thrombosis. This research is focused on developing a bidirectional dual drug-eluting stent to co-deliver an anti-proliferative agent (paclitaxel - PAT) and an endothelial cell promoting agent (nitric oxide - NO) from abluminal and luminal surfaces of the stent, respectively. Phosphonoacetic acid, a polymer-free drug delivery platform, was initially coated on the stents. Then, the PAT and NO donor drugs were co-coated on the abluminal and luminal stent surfaces, respectively. The co-coating of drugs was collectively confirmed by the surface characterization techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), 3D optical surface profilometry, and contact angle goniometry. SEM showed that the integrity of the co-coating of drugs was maintained without delamination or cracks formation occurring during the stent expansion experiments. In vitro drug release studies showed that the PAT was released from the abluminal stent surfaces in a biphasic manner, which is an initial burst followed by a slow and sustained release. The NO was burst released from the luminal stent surfaces. Thus, this study demonstrated the co-delivery of PAT and NO from abluminal and luminal stent surfaces, respectively. The stent developed in this study has potential applications in inhibiting neointimal hyperplasia as well as encouraging luminal endothelialization to prevent late stent thrombosis.

Clinical features associated with copy number variations of the 14q32 imprinted gene cluster.

PubMed

Rosenfeld, Jill A; Fox, Joyce E; Descartes, Maria; Brewer, Fallon; Stroud, Tracy; Gorski, Jerome L; Upton, Sheila J; Moeschler, John B; Monteleone, Berrin; Neill, Nicholas J; Lamb, Allen N; Ballif, Blake C; Shaffer, Lisa G; Ravnan, J Britt

2015-02-01

Uniparental disomy (UPD) for imprinted chromosomes can cause abnormal phenotypes due to absent or overexpression of imprinted genes. UPD(14)pat causes a unique constellation of features including thoracic skeletal anomalies, polyhydramnios, placentomegaly, and limited survival; its hypothesized cause is overexpression of paternally expressed RTL1, due to absent regulatory effects of maternally expressed RTL1as. UPD(14)mat causes a milder condition with hypotonia, growth failure, and precocious puberty; its hypothesized cause is absence of paternally expressed DLK1. To more clearly establish how gains and losses of imprinted genes can cause disease, we report six individuals with copy number variations of the imprinted 14q32 region identified through clinical microarray-based comparative genomic hybridization. Three individuals presented with UPD(14)mat-like phenotypes (Temple syndrome) and had apparently de novo deletions spanning the imprinted region, including DLK1. One of these deletions was shown to be on the paternal chromosome. Two individuals with UPD(14)pat-like phenotypes had 122-154kb deletions on their maternal chromosomes that included RTL1as but not the differentially methylated regions that regulate imprinted gene expression, providing further support for RTL1 overexpression as a cause for the UPD(14)pat phenotype. The sixth individual is tetrasomic for a 1.7Mb segment, including the imprinted region, and presents with intellectual disability and seizures but lacks significant phenotypic overlap with either UPD(14) syndrome. Therefore, the 14q32 imprinted region is dosage sensitive, with deletions of different critical regions causing UPD(14)mat- and UPD(14)pat-like phenotypes, while copy gains are likely insufficient to recapitulate these phenotypes.

Real time optical coherence tomography monitoring of Candida albicans biofilm in vitro during photodynamic treatment

NASA Astrophysics Data System (ADS)

Suzuki, Luis Cláudio; Araujo Prates, Renato; Raele, Marcus Paulo; Zanardi di Freitas, Anderson; Simões Ribeiro, Martha

2010-04-01

The biofilm formed by Candida albicans is the mainly cause of infections associated to medical devices such as catheters. Studies have shown that photodynamic antimicrobial therapy (PAT) has lethal effect on C. albicans, and it is based on photosensitizer (PS) in the presence of low intensity light to generate reactive oxygen species in biological systems. The aim of this study was to analyze in real time, by Optical Coherence Tomography (OCT), the alterations in C. albicans biofilm in vitro during PAT using methylene blue (MB) as a PS and red light. An OCT system with working at 930nm was used, sequential images of 2000×512 pixels were generated at the frame rate of 2.5frames/sec. The dimension of the analyzed sample was 6000μm wide by 1170μm of depth corrected by refraction index of 1.35. We recorded 1min. before and after the irradiation with LED for PAT, generating 8min. of video. For biofilm formation, discs were made from elastomeric silicone catheters. The PS was dissolved in PBS solution, and a final concentration of 1mM MB was applied on biofilm, followed by a red LED irradiation (λ=630nm+/-20nm) during 6min. We performed a curve of survival fraction versus time of irradiation and it was reduced by 100% following 6min. of irradiation. OCT was performed for measurement of biofilm thickness of 110μm when biofilm was formed. During irradiation, the variation of biofilm thickness was ~70μm. We conclude that OCT system is able to show real time optical changes provided by PAT in yeasts organized in biofilm.

Modelling the dynamics of polar auxin transport in inflorescence stems of Arabidopsis thaliana

PubMed Central

Boot, Kees J.M.; Hille, Sander C.; Libbenga, Kees R.; Peletier, Lambertus A.; van Spronsen, Paulina C.; van Duijn, Bert; Offringa, Remko

2016-01-01

The polar transport of the plant hormone auxin has been the subject of many studies, several involving mathematical modelling. Unfortunately, most of these models have not been experimentally verified. Here we present experimental measurements of long-distance polar auxin transport (PAT) in segments of inflorescence stems of Arabidopsis thaliana together with a descriptive mathematical model that was developed from these data. It is based on a general advection–diffusion equation for auxin density, as suggested by the chemiosmotic theory, but is extended to incorporate both immobilization of auxin and exchange with the surrounding tissue of cells involved in PAT, in order to account for crucial observations. We found that development of the present model assisted effectively in the analysis of experimental observations. As an example, we discuss the analysis of a quadruple mutant for all four AUX1/LAX1–LAX3 influx carriers genes. We found a drastic change in the parameters governing the exchange of PAT channels with the surrounding tissue, whereas the velocity was still of the order of magnitude of the wild type. In addition, the steady-state flux of auxin through the PAT system of the mutant did not exhibit a saturable component, as we found for the wild type, suggesting that the import carriers are responsible for the saturable component in the wild type. In the accompanying Supplementary data available at JXB online, we describe in more detail the data-driven development of the model, review and derive predictions from a mathematical model of the chemiosmotic theory, and explore relationships between parameters in our model and processes and parameters at the cellular level. PMID:26531101

Prevalence and Virulence Factors of Escherichia coli Serogroups O26, O103, O111, and O145 Shed by Cattle in Scotland

PubMed Central

Pearce, M. C.; Evans, J.; McKendrick, I. J.; Smith, A. W.; Knight, H. I.; Mellor, D. J.; Woolhouse, M. E. J.; Gunn, G. J.; Low, J. C.

2006-01-01

A national survey was conducted to determine the prevalence of Escherichia coli O26, O103, O111, and O145 in feces of Scottish cattle. In total, 6,086 fecal pats from 338 farms were tested. The weighted mean percentages of farms on which shedding was detected were 23% for E. coli O26, 22% for E. coli O103, and 10% for E. coli O145. The weighted mean prevalences in fecal pats were 4.6% for E. coli O26, 2.7% for E. coli O103, and 0.7% for E. coli O145. No E. coli O111 was detected. Farms with cattle shedding E. coli serogroup O26, O103, or O145 were widely dispersed across Scotland and were identified most often in summer and autumn. However, on individual farms, fecal shedding of E. coli O26, O103, or O145 was frequently undetectable or the numbers of pats testing positive were small. For serogroup O26 or O103 there was clustering of positive pats within management groups, and the presence of an animal shedding one of these serogroups was a positive predictor for shedding by others, suggesting local transmission of infection. Carriage of vtx was rare in E. coli O103 and O145 isolates, but 49.0% of E. coli O26 isolates possessed vtx, invariably vtx1 alone or vtx1 and vtx2 together. The carriage of eae and ehxA genes was highly associated in all three serogroups. Among E. coli serogroup O26 isolates, 28.9% carried vtx, eae, and ehxA—a profile consistent with E. coli O26 strains known to cause human disease. PMID:16391103

NetpathXL - An Excel Interface to the Program NETPATH

USGS Publications Warehouse

Parkhurst, David L.; Charlton, Scott R.

2008-01-01

NetpathXL is a revised version of NETPATH that runs under Windows? operating systems. NETPATH is a computer program that uses inverse geochemical modeling techniques to calculate net geochemical reactions that can account for changes in water composition between initial and final evolutionary waters in hydrologic systems. The inverse models also can account for the isotopic composition of waters and can be used to estimate radiocarbon ages of dissolved carbon in ground water. NETPATH relies on an auxiliary, database program, DB, to enter the chemical analyses and to perform speciation calculations that define total concentrations of elements, charge balance, and redox state of aqueous solutions that are then used in inverse modeling. Instead of DB, NetpathXL relies on Microsoft Excel? to enter the chemical analyses. The speciation calculation formerly included in DB is implemented within the program NetpathXL. A program DBXL can be used to translate files from the old DB format (.lon files) to NetpathXL spreadsheets, or to create new NetpathXL spreadsheets. Once users have a NetpathXL spreadsheet with the proper format, new spreadsheets can be generated by copying or saving NetpathXL spreadsheets. In addition, DBXL can convert NetpathXL spreadsheets to PHREEQC input files. New capabilities in PHREEQC (version 2.15) allow solution compositions to be written to a .lon file, and inverse models developed in PHREEQC to be written as NetpathXL .pat and model files. NetpathXL can open NetpathXL spreadsheets, NETPATH-format path files (.pat files), and NetpathXL-format path files (.pat files). Once the speciation calculations have been performed on a spreadsheet file or a .pat file has been opened, the NetpathXL calculation engine is identical to the original NETPATH. Development of models and viewing results in NetpathXL rely on keyboard entry as in NETPATH.

Dispersion and Transport of Cryptosporidium Oocysts from Fecal Pats under Simulated Rainfall Events

PubMed Central

Davies, Cheryl M.; Ferguson, Christobel M.; Kaucner, Christine; Krogh, Martin; Altavilla, Nanda; Deere, Daniel A.; Ashbolt, Nicholas J.

2004-01-01

The dispersion and initial transport of Cryptosporidium oocysts from fecal pats were investigated during artificial rainfall events on intact soil blocks (1,500 by 900 by 300 mm). Rainfall events of 55 mm h−1 for 30 min and 25 mm h−1 for 180 min were applied to soil plots with artificial fecal pats seeded with approximately 107 oocysts. The soil plots were divided in two, with one side devoid of vegetation and the other left with natural vegetation cover. Each combination of event intensity and duration, vegetation status, and degree of slope (5° and 10°) was evaluated twice. Generally, a fivefold increase (P < 0.05) in runoff volume was generated on bare soil compared to vegetated soil, and significantly more infiltration, although highly variable, occurred through the vegetated soil blocks (P < 0.05). Runoff volume, event conditions (intensity and duration), vegetation status, degree of slope, and their interactions significantly affected the load of oocysts in the runoff. Surface runoff transported from 100.2 oocysts from vegetated loam soil (25-mm h−1, 180-min event on 10° slope) to up to 104.5 oocysts from unvegetated soil (55-mm h−1, 30-min event on 10° slope) over a 1-m distance. Surface soil samples downhill of the fecal pat contained significantly higher concentrations of oocysts on devegetated blocks than on vegetated blocks. Based on these results, there is a need to account for surface soil vegetation coverage as well as slope and rainfall runoff in future assessments of Cryptosporidium transport and when managing pathogen loads from stock grazing near streams within drinking water watersheds. PMID:14766600

Inconsistent Correlation Between Carotid Artery Intima-Media Thickness and Peripheral Arterial Tonometry

PubMed Central

Lemos, Sara P.; Passos, Valéria Maria A.; Brant, Luisa C.C.; Bensenor, Isabela J.M.; Ribeiro, Antônio Luiz P.; Barreto, Sandhi Maria

2015-01-01

Abstract To estimate the association between 2 markers for atherosclerosis, measurements of carotid artery intima-media thickness (IMT) and of peripheral arterial tonometry (PAT), and to evaluate the role of traditional cardiovascular risk factors in this association. We applied the 2 diagnostic tests to 588 participants from the ELSA-Brazil longitudinal study cohort. The PAT measurements, obtained with the EndoPAT2000, were the reactive hyperemia index (RHI), the Framingham RHI (F-RHI), and the mean basal pulse amplitude (BPA). We used the mean of the mean scores of carotid IMT of the distal layers of the left and right common carotids obtained by ultrasonography after 3 cardiac cycles. We used linear regression and the Spearman correlation coefficient to test the relationship between the 2 markers, and multiple linear regressions to exam the relationship between the RHI/F-RHI scores and the mean BPA and IMT scores after adjusting for cardiovascular risk factors. In the multivariate analysis, RHI (but not F-RHI) was positively correlated with the mean of the means of the IMT values after adjusting for sex and risk factors connected with both measures (β = 0.05, P = 0.02). Mean BPA did not remain significantly associated with IMT after adjusting for common risk factors. We found that the higher the IMT (or the worse the IMT), the higher the RHI (or the better the endothelial function). F-RHI was not associated with IMT. These 2 results are against the direction that one would expect and may imply that digital endothelial function (RHI and F-RHI) and IMT correspond to distinct and independent stages of the complex atherosclerosis process and represent different pathways in the disease's progression. Therefore, IMT and PAT measures may be considered complementary and not interchangeable. PMID:26287431

Root transcriptional responses of two melon genotypes with contrasting resistance to Monosporascus cannonballus (Pollack et Uecker) infection.

PubMed

Roig, Cristina; Fita, Ana; Ríos, Gabino; Hammond, John P; Nuez, Fernando; Picó, Belén

2012-11-08

Monosporascus cannonballus is the main causal agent of melon vine decline disease. Several studies have been carried out mainly focused on the study of the penetration of this pathogen into melon roots, the evaluation of symptoms severity on infected roots, and screening assays for breeding programs. However, a detailed molecular view on the early interaction between M. cannonballus and melon roots in either susceptible or resistant genotypes is lacking. In the present study, we used a melon oligo-based microarray to investigate the gene expression responses of two melon genotypes, Cucumis melo 'Piel de sapo' ('PS') and C. melo 'Pat 81', with contrasting resistance to the disease. This study was carried out at 1 and 3 days after infection (DPI) by M. cannonballus. Our results indicate a dissimilar behavior of the susceptible vs. the resistant genotypes from 1 to 3 DPI. 'PS' responded with a more rapid infection response than 'Pat 81' at 1 DPI. At 3 DPI the total number of differentially expressed genes identified in 'PS' declined from 451 to 359, while the total number of differentially expressed transcripts in 'Pat 81' increased from 187 to 849. Several deregulated transcripts coded for components of Ca2+ and jasmonic acid (JA) signalling pathways, as well as for other proteins related to defence mechanisms. Transcriptional differences in the activation of the JA-mediated response in 'Pat 81' compared to 'PS' suggested that JA response might be partially responsible for their observed differences in resistance. As a result of this study we have identified for the first time a set of candidate genes involved in the root response to the infection of the pathogen causing melon vine decline. This information is useful for understanding the disease progression and resistance mechanisms few days after inoculation.