Modeling Adaptable Business Service for Enterprise Collaboration

NASA Astrophysics Data System (ADS)

Boukadi, Khouloud; Vincent, Lucien; Burlat, Patrick

Nowadays, a Service Oriented Architecture (SOA) seems to be one of the most promising paradigms for leveraging enterprise information systems. SOA creates opportunities for enterprises to provide value added service tailored for on demand enterprise collaboration. With the emergence and rapid development of Web services technologies, SOA is being paid increasing attention and has become widespread. In spite of the popularity of SOA, a standardized framework for modeling and implementing business services are still in progress. For the purpose of supporting these service-oriented solutions, we adopt a model driven development approach. This paper outlines the Contextual Service Oriented Modeling and Analysis (CSOMA) methodology and presents UML profiles for the PIM level service-oriented architectural modeling, as well as its corresponding meta-models. The proposed PIM (Platform Independent Model) describes the business SOA at a high level of abstraction regardless of techniques involved in the application employment. In addition, all essential service-specific concerns required for delivering quality and context-aware service are covered. Some of the advantages of this approach are that it is generic and thus not closely allied with Web service technology as well as specifically treating the service adaptability during the design stage.

77 FR 46790 - Environmental Impact Statement: Dane County, WI

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-06

... input on the project's Coordination Plan (CP) and Impact Assessment Methodology (IAM) were afforded to.... Public input was obtained on the draft project CP and IAM plan at the October 2007 Public Information Meeting (PIM). The completed project CP and IAM plan was issued in October 2008. A follow-up Agency...

The association of change in medication regimen and use of inappropriate medication based on beers criteria with adverse outcomes in Japanese long-term care facilities.

PubMed

Ishii, Shinya; Kojima, Taro; Ezawa, Kazuhiko; Higashi, Kentaro; Ikebata, Yukihiko; Takehisa, Yozo; Akishita, Masahiro

2017-04-01

To describe medication use including potentially inappropriate medication (PIM) and examine the association between adverse outcomes and patient factors including PIM use in Japanese elderly patients in long-term care facilities. This was a retrospective cohort study of 470 patients in 53 Geriatric Health Service Facilities and 44 Sanatorium Type Medical Care Facilities for the Elderly Requiring Long Term Care. Standardized forms were used to collect information including oral and parenteral medication use on admission, and 1 month and 3 months after admission. PIMs were determined by the 2003 or 2012 Beers criteria. Adverse outcomes were any medical events leading to emergency department transfer, hospitalization to acute care hospitals or death. A total of 2,227 oral medications and 197 parenteral medications were prescribed for 470 patients on admission. PIM exposure based on the 2003 and 2012 Beers criteria was observed in 11.9% and 37.5%, respectively. Adverse outcomes within 3 months after admission were observed in 8.9% of the entire cohort, and were associated with age, sex, facility type and number of parenteral medications on admission. Adverse outcomes between one and three months after admission were associated with age, sex, number of parenteral medications at one month, and a change in the number of oral and parenteral medications within one month after admission. PIM exposure was not associated with adverse outcomes in any models. Use of PIM was prevalent in long-term care facilities. Our findings support the importance of comprehensive assessment of medication regimens including parenteral medication. Geriatr Gerontol Int 2017; 17: 591-597. © 2016 Japan Geriatrics Society.

The role of PIM1/PIM2 kinases in tumors of the male reproductive system.

PubMed

Jiménez-García, Manuel Pedro; Lucena-Cacace, Antonio; Robles-Frías, María José; Narlik-Grassow, Maja; Blanco-Aparicio, Carmen; Carnero, Amancio

2016-11-30

The PIM family of serine/threonine kinases has three highly conserved isoforms (PIM1, PIM2 and PIM3). PIM proteins are regulated through transcription and stability by JAK/STAT pathways and are overexpressed in hematological malignancies and solid tumors. The PIM kinases possess weak oncogenic abilities, but enhance other genes or chemical carcinogens to induce tumors. We generated conditional transgenic mice that overexpress PIM1 or PIM2 in male reproductive organs and analyzed their contribution to tumorigenesis. We found an increase in alterations of sexual organs and hyperplasia in the transgenic mice correlating with inflammation. We also found that PIM1/2 are overexpressed in a subset of human male germ cells and prostate tumors correlating with inflammatory features and stem cell markers. Our data suggest that PIM1/2 kinase overexpression is a common feature of male reproductive organs tumors, which provoke tissue alterations and a large inflammatory response that may act synergistically during the process of tumorigenesis. There is also a correlation with markers of cancer stem cells, which may contribute to the therapy resistance found in tumors overexpressing PIM kinases.

Pre-clinical evidence of PIM kinase inhibitor activity in BCR-ABL1 unmutated and mutated Philadelphia chromosome-positive (Ph+) leukemias

PubMed Central

Curi, Dany A.; Beauchamp, Elspeth M.; Blyth, Gavin T.; Arslan, Ahmet Dirim; Donato, Nicholas J.; Giles, Francis J.; Altman, Jessica K.; Platanias, Leonidas C.

2015-01-01

We investigated the efficacy of targeting the PIM kinase pathway in Philadelphia chromosome-positive (Ph+) leukemias. We provide evidence that inhibition of PIM, with the pan-PIM inhibitor SGI-1776, results in suppression of classic PIM effectors and also elements of the mTOR pathway, suggesting interplay between PIM and mTOR signals. Our data demonstrate that PIM inhibition enhances the effects of imatinib mesylate on Ph+ leukemia cells. We also found that PIM inhibition results in suppression of leukemic cell proliferation and induction of apoptosis of Ph+ leukemia cells, including those resistant to imatinib mesylate. Importantly, inhibition of PIM results in enhanced suppression of primary leukemic progenitors from patients with CML. Altogether these findings suggest that pharmacological PIM targeting may provide a unique therapeutic approach for the treatment of Ph+ leukemias. PMID:26375673

Potentially inappropriate medicines in elderly hospitalised patients according to the EU(7)-PIM list, STOPP version 2 criteria and comprehensive protocol.

PubMed

Mucalo, Iva; Hadžiabdić, Maja Ortner; Brajković, Andrea; Lukić, Sonja; Marić, Patricia; Marinović, Ivana; Bačić-Vrca, Vesna

2017-08-01

The aim of this study was to measure the prevalence of potentially inappropriate medications (PIMs) by using the EU(7)-PIM list, STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions) version 2 criteria and the new comprehensive protocol. This prospective study involved a sample of 276 consecutive elderly patients discharged from the university teaching hospital. Age, gender, diagnoses, medication history and medicines at discharge were recorded. The main outcome measure was the prevalence of PIMs according to each set of criteria: EU(7)-PIM list, STOPP version 2 criteria and comprehensive protocol. The median patient age (range) was 74 (65-92) years. The median number of prescribed medications was 7 (1-17). STOPP identified 393 PIMs affecting 190 patients (69%), EU(7)-PIM list identified 330 PIMs in 184 patients (66.7%) whilst the comprehensive protocol identified 134 PIMs in 102 patients (37%). STOPP version 2 criteria identified significantly more PIMs per patient than the other two protocols (p < 0.001). Gender (p = 0.002), glomerular filtration rate (p = 0.039) and number of comorbidities (p = 0.001) were associated with the proportion of PIMs for the STOPP version 2 criteria only. A very high PIM prevalence at discharge was reported suggesting the urgent need for actions to reduce them. STOPP version 2 criteria identified significantly more PIMs than the EU(7)-PIM list and the comprehensive protocol and was found as a more sensitive tool for PIM detection.

A comparison of two tools to screen potentially inappropriate medication in internal medicine patients.

PubMed

Blanc, A-L; Spasojevic, S; Leszek, A; Théodoloz, M; Bonnabry, P; Fumeaux, T; Schaad, N

2018-04-01

Potentially inappropriate medication (PIM) is an important issue for inpatient management; it has been associated with safety problems, such as increases in adverse drugs events, and with longer hospital stays and higher healthcare costs. To compare two PIM-screening tools-STOPP/START and PIM-Check-applied to internal medicine patients. A second objective was to compare the use of PIMs in readmitted and non-readmitted patients. A retrospective observational study, in the general internal medicine ward of a Swiss non-university hospital. We analysed a random sample of 50 patients, hospitalized in 2013, whose readmission within 30 days of discharge had been potentially preventable, and compared them to a sample of 50 sex- and age-matched patients who were not readmitted. PIMs were screened using the STOPP/START tool, developed for geriatric patients, and the PIM-Check tool, developed for internal medicine patients. The time needed to perform each patient's analysis was measured. A clinical pharmacist counted and evaluated each PIM detected, based on its clinical relevance to the individual patient's case. The rates of screened and validated PIMs involving readmitted and non-readmitted patients were compared. Across the whole population, PIM-Check and STOPP/START detected 1348 and 537 PIMs, respectively, representing 13.5 and 5.4 PIMs/patient. Screening time was substantially shorter with PIM-Check than with STOPP/START (4 vs 10 minutes, respectively). The clinical pharmacist judged that 45% and 42% of the PIMs detected using PIM-Check and STOPP/START, respectively, were clinically relevant to individual patients' cases. No significant differences in the rates of detected and clinically relevant PIM were found between readmitted and non-readmitted patients. Internal medicine patients are frequently prescribed PIMs. PIM-Check's PIM detection rate was three times higher than STOPP/START's, and its screening time was shorter thanks to its electronic interface. Nearly half of the PIMs detected were judged to be non-clinically relevant, however, potentially overalerting the prescriber. These tools can, nevertheless, be considered useful in daily practice. Furthermore, the relevance of any PIM detected by these tools should always be carefully evaluated within the clinical context surrounding the individual patient. © 2017 John Wiley & Sons Ltd.

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

Walpen, Thomas; Kalus, Ina; Schwaller, Juerg

Highlights: Black-Right-Pointing-Pointer Pim1{sup -/-} endothelial cell proliferation displays increased sensitivity to rapamycin. Black-Right-Pointing-Pointer mTOR inhibition by rapamycin enhances PIM1 cytosolic and nuclear protein levels. Black-Right-Pointing-Pointer Truncation of Pim1 beyond serine 276 results in nuclear localization of the kinase. Black-Right-Pointing-Pointer Nuclear PIM1 increases endothelial proliferation independent of rapamycin. -- Abstract: The PIM serine/threonine kinases and the mTOR/AKT pathway integrate growth factor signaling and promote cell proliferation and survival. They both share phosphorylation targets and have overlapping functions, which can partially substitute for each other. In cancer cells PIM kinases have been reported to produce resistance to mTOR inhibition by rapamycin. Tumormore » growth depends highly on blood vessel infiltration into the malignant tissue and therefore on endothelial cell proliferation. We therefore investigated how the PIM1 kinase modulates growth inhibitory effects of rapamycin in mouse aortic endothelial cells (MAEC). We found that proliferation of MAEC lacking Pim1 was significantly more sensitive to rapamycin inhibition, compared to wildtype cells. Inhibition of mTOR and AKT in normal MAEC resulted in significantly elevated PIM1 protein levels in the cytosol and in the nucleus. We observed that truncation of the C-terminal part of Pim1 beyond Ser 276 resulted in almost exclusive nuclear localization of the protein. Re-expression of this Pim1 deletion mutant significantly increased the proliferation of Pim1{sup -/-} cells when compared to expression of the wildtype Pim1 cDNA. Finally, overexpression of the nuclear localization mutant and the wildtype Pim1 resulted in complete resistance to growth inhibition by rapamycin. Thus, mTOR inhibition-induced nuclear accumulation of PIM1 or expression of a nuclear C-terminal PIM1 truncation mutant is sufficient to increase endothelial cell proliferation, suggesting that nuclear localization of PIM1 is important for resistance of MAEC to rapamycin-mediated inhibition of proliferation.« less

An introduction to the new Productivity Information Management System (PIMS)

NASA Technical Reports Server (NTRS)

Hull, R.

1982-01-01

The productivity information management system (PIMS), is described. The main objective of this computerized system is to enable management scientists to interactively explore data concerning DSN operations, maintenance and repairs, to develop and verify models for management planning. The PIMS will provide a powerful set of tools for iteratively manipulating data sets in a wide variety of ways. The initial version of PIMS will be a small scale pilot system. The following topics are discussed: (1) the motivation for developing PIMS; (2) various data sets which will be integrated by PIMS; (3) overall design of PIMS; and (4) how PIMS will be used. A survey of relevant databases concerning DSN operations at Goldstone is also included.

Up-regulation of Pim-3 in Chronic Obstructive Pulmonary Disease (COPD) patients and its potential therapeutic role in COPD rat modeling.

PubMed

Yang, Cheng; Li, Li; Guo, Junhua; Zhang, Weiqiang; Zhu, Wenbiao; Rao, Xinhui; Huang, Wenjie

2017-04-01

Pim-3 belongs to the PIM kinase family and plays an important role in promoting inflammation, which is essential in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Immunohistochemistry (IHC), western blot, and RT-PCR analyses were performed to assess the expression of Pim-3 in both COPD and healthy lung tissue samples. SMA (Smooth Muscle Actin) and Cyclin D1 expression were detected by IHC. We also constructed animal models for the control, COPD, and Pim-3 inhibition groups, in order to analyze the effects of Pim-3 inhibition on COPD, and the role of Pim-3 in the p38 pathway. Compared with normal lung tissue, Pim-3 mRNA and protein were up-regulated in COPD tissue. Expression of Cyclin D1 and SMA were also up-regulated in the COPD group. In the animal model experiment, we found that suppression of Pim-3 decreased Pim-3, Cyclin D1, and SMA expression, as well as ameliorated lung damage in COPD patients. The inhibition of Pim-3 also resulted in the suppression of the p38 pathway. Our study suggests that up-regulation of Pim-3 successfully accelerated COPD development, and aggravated lung damage. The molecular mechanism of Pim-3 in COPD might be related to the p38 pathway, and is correlated with Cyclin D1 and SMA expression. Copyright © 2017 Elsevier GmbH. All rights reserved.

Localized traveling ionization zones and their importance for the high power impulse magnetron sputtering process

NASA Astrophysics Data System (ADS)

Maszl, Christian

2016-09-01

High power impulse magnetron sputtering (HiPIMS) is a technique to deposit thin films with superior quality. A high ionization degree up to 90% and the natural occurence of high energetic metal ions are the reason why HiPIMS exceeds direct current magnetron sputtering in terms of coating quality. On the other hand HiPIMS suffers from a reduced efficiency, especially if metal films are produced. Therefore, a lot of research is done by experimentalists and theoreticians to clarify the transport mechanisms from target to substrate and to identify the energy source of the energetic metal ions. Magnetron plasmas are prone to a wide range of wave phenomena and instabilities. Especially, during HiPIMS at elevated power/current densities, symmetry breaks and self-organization in the plasma torus are observed. In this scenario localized travelling ionization zones with certain quasi-mode numbers are present which are commonly referred to as spokes. Because of their high rotation speed compared to typical process times of minutes their importance for thin film deposition was underestimated at first. Recent investigations show that spokes have a strong impact on particle transport, are probably the source of the high energetic metal ions and are therefore the essence of HiPIMS plasmas. In this contribution we will describe the current understanding of spokes, discuss implications for thin film synthesis and highlight open questions. This project is supported by the DFG (German Science Foundation) within the framework of the Coordinated Research Center SFB-TR 87 and the Research Department ``Plasmas with Complex Interactions'' at Ruhr-University Bochum.

Functional Effect of Pim1 Depends upon Intracellular Localization in Human Cardiac Progenitor Cells

PubMed Central

Samse, Kaitlen; Emathinger, Jacqueline; Hariharan, Nirmala; Quijada, Pearl; Ilves, Kelli; Völkers, Mirko; Ormachea, Lucia; De La Torre, Andrea; Orogo, Amabel M.; Alvarez, Roberto; Din, Shabana; Mohsin, Sadia; Monsanto, Megan; Fischer, Kimberlee M.; Dembitsky, Walter P.; Gustafsson, Åsa B.; Sussman, Mark A.

2015-01-01

Human cardiac progenitor cells (hCPC) improve heart function after autologous transfer in heart failure patients. Regenerative potential of hCPCs is severely limited with age, requiring genetic modification to enhance therapeutic potential. A legacy of work from our laboratory with Pim1 kinase reveals effects on proliferation, survival, metabolism, and rejuvenation of hCPCs in vitro and in vivo. We demonstrate that subcellular targeting of Pim1 bolsters the distinct cardioprotective effects of this kinase in hCPCs to increase proliferation and survival, and antagonize cellular senescence. Adult hCPCs isolated from patients undergoing left ventricular assist device implantation were engineered to overexpress Pim1 throughout the cell (PimWT) or targeted to either mitochondrial (Mito-Pim1) or nuclear (Nuc-Pim1) compartments. Nuc-Pim1 enhances stem cell youthfulness associated with decreased senescence-associated β-galactosidase activity, preserved telomere length, reduced expression of p16 and p53, and up-regulation of nucleostemin relative to PimWT hCPCs. Alternately, Mito-Pim1 enhances survival by increasing expression of Bcl-2 and Bcl-XL and decreasing cell death after H2O2 treatment, thereby preserving mitochondrial integrity superior to PimWT. Mito-Pim1 increases the proliferation rate by up-regulation of cell cycle modulators Cyclin D, CDK4, and phospho-Rb. Optimal stem cell traits such as proliferation, survival, and increased youthful properties of aged hCPCs are enhanced after targeted Pim1 localization to mitochondrial or nuclear compartments. Targeted Pim1 overexpression in hCPCs allows for selection of the desired phenotypic properties to overcome patient variability and improve specific stem cell characteristics. PMID:25882843

Functional Effect of Pim1 Depends upon Intracellular Localization in Human Cardiac Progenitor Cells.

PubMed

Samse, Kaitlen; Emathinger, Jacqueline; Hariharan, Nirmala; Quijada, Pearl; Ilves, Kelli; Völkers, Mirko; Ormachea, Lucia; De La Torre, Andrea; Orogo, Amabel M; Alvarez, Roberto; Din, Shabana; Mohsin, Sadia; Monsanto, Megan; Fischer, Kimberlee M; Dembitsky, Walter P; Gustafsson, Åsa B; Sussman, Mark A

2015-05-29

Human cardiac progenitor cells (hCPC) improve heart function after autologous transfer in heart failure patients. Regenerative potential of hCPCs is severely limited with age, requiring genetic modification to enhance therapeutic potential. A legacy of work from our laboratory with Pim1 kinase reveals effects on proliferation, survival, metabolism, and rejuvenation of hCPCs in vitro and in vivo. We demonstrate that subcellular targeting of Pim1 bolsters the distinct cardioprotective effects of this kinase in hCPCs to increase proliferation and survival, and antagonize cellular senescence. Adult hCPCs isolated from patients undergoing left ventricular assist device implantation were engineered to overexpress Pim1 throughout the cell (PimWT) or targeted to either mitochondrial (Mito-Pim1) or nuclear (Nuc-Pim1) compartments. Nuc-Pim1 enhances stem cell youthfulness associated with decreased senescence-associated β-galactosidase activity, preserved telomere length, reduced expression of p16 and p53, and up-regulation of nucleostemin relative to PimWT hCPCs. Alternately, Mito-Pim1 enhances survival by increasing expression of Bcl-2 and Bcl-XL and decreasing cell death after H2O2 treatment, thereby preserving mitochondrial integrity superior to PimWT. Mito-Pim1 increases the proliferation rate by up-regulation of cell cycle modulators Cyclin D, CDK4, and phospho-Rb. Optimal stem cell traits such as proliferation, survival, and increased youthful properties of aged hCPCs are enhanced after targeted Pim1 localization to mitochondrial or nuclear compartments. Targeted Pim1 overexpression in hCPCs allows for selection of the desired phenotypic properties to overcome patient variability and improve specific stem cell characteristics. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.

PubMed

Liu, Jing; Qu, Xinyu; Shao, Liwei; Hu, Yuan; Yu, Xin; Lan, Peixiang; Guo, Qie; Han, Qiuju; Zhang, Jian; Zhang, Cai

2018-03-04

Melanoma is the deadliest form of commonly encountered skin cancer, and has fast propagating and highly invasive characteristics. Pim-3, a highly expressed oncogene in melanoma, is a highly conserved serine/threonine kinase with various biological activities, such as proliferation-accelerating and anti-apoptosis effects on cancer progression. However, whether Pim-3 regulates melanoma metastasis has not been determined. Here, we constructed a Pim-3-silencing short hairpin RNA (sh-Pim-3), a TLR7-stimulating ssRNA and a dual-function vector containing a sh-Pim-3 and a ssRNA, and transfected them into the B16F10 melanoma cell line to investigate the effects of Pim-3 on migration and invasion in melanoma. We found that sh-Pim-3 inhibited B16F10 cell migration and invasion in vitro. In a tumor-bearing mouse model, sh-Pim-3 significantly downregulated pulmonary metastasis of B16F10 melanoma cell in vivo. Mechanistically, sh-Pim-3 inhibited metastasis by regulating the expression of genes related to epithelial-mesenchymal transition (EMT). Further study revealed that by promoting the phosphorylation of STAT3 (signal transducer and activator of transcription 3), Pim-3 induced the expression of Slug, Snail, and ZEB1, which enhanced EMT-related changes and induced melanoma migration and invasion. Our study suggests that Pim-3 is a potential effective target for melanoma therapy.

The Pim kinases: new targets for drug development.

PubMed

Swords, Ronan; Kelly, Kevin; Carew, Jennifer; Nawrocki, Stefan; Mahalingam, Devalingam; Sarantopoulos, John; Bearss, David; Giles, Francis

2011-12-01

The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to cancer development and progression. They were first recognized as pro-viral integration sites for the Moloney Murine Leukemia virus. Unlike other kinases, they possess a hinge region which creates a unique binding pocket for ATP. Absence of a regulatory domain means that these proteins are constitutively active once transcribed. Pim kinases are critical downstream effectors of the ABL (ableson), JAK2 (janus kinase 2), and Flt-3 (FMS related tyrosine kinase 1) oncogenes and are required by them to drive tumorigenesis. Recent investigations have established that the Pim kinases function as effective inhibitors of apoptosis and when overexpressed, produce resistance to the mTOR (mammalian target of rapamycin) inhibitor, rapamycin . Overexpression of the PIM kinases has been reported in several hematological and solid tumors (PIM 1), myeloma, lymphoma, leukemia (PIM 2) and adenocarcinomas (PIM 3). As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Novel small molecule inhibitors of the human Pim kinases have been designed and are currently undergoing preclinical evaluation.

Health Outcomes Associated With Potentially Inappropriate Medication Use in Older Adults

PubMed Central

Fick, Donna M.; Mion, Lorraine C.; Beers, Mark H.; Waller, Jennifer L.

2008-01-01

The purpose of this study was to examine the prevalence of potentially inappropriate medication use (PIMs) among community-dwelling older adults and the association between PIMs and health care outcomes. Participants were 17,971 individuals age 65 years and older. PIM use was defined by the Beers criteria. Drug-related problems (DRPs) were defined using ICD-9 codes. Forty percent of the 17,971 individuals filled at least 1 PIM prescription, and 13% filled 2 or more PIM prescriptions. Overall DRP prevalence among those with at least 1 PIM prescription was 14.3% compared to 4.7% in the non-PIM group (p < .001). In conclusion, preventing PIM use may be important for decreasing medication-related problems, which are increasingly being recognized as requiring an integrated interdisciplinary approach. PMID:18163447

Pim kinases are upregulated during Epstein-Barr virus infection and enhance EBNA2 activity

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

Rainio, Eeva-Marja; Turku Graduate School of Biomedical Sciences, 20520 Turku; Ahlfors, Helena

Latent Epstein-Barr virus (EBV) infection is strongly associated with B-cell proliferative diseases such as Burkitt's lymphoma. Here we show that the oncogenic serine/threonine kinases Pim-1 and Pim-2 enhance the activity of the viral transcriptional activator EBNA2. During EBV infection of primary B-lymphocytes, the mRNA expression levels of pim genes, especially of pim-2, are upregulated and remain elevated in latently infected B-cell lines. Thus, EBV-induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional activity may contribute to the ability of EBV to immortalize B-cells and predispose them to malignant growth.

Pim Kinases Promote Migration and Metastatic Growth of Prostate Cancer Xenografts

PubMed Central

Santio, Niina M.; Eerola, Sini K.; Paatero, Ilkka; Yli-Kauhaluoma, Jari; Anizon, Fabrice; Moreau, Pascale; Tuomela, Johanna; Härkönen, Pirkko; Koskinen, Päivi J.

2015-01-01

Background and methods Pim family proteins are oncogenic kinases implicated in several types of cancer and involved in regulation of cell proliferation, survival as well as motility. Here we have investigated the ability of Pim kinases to promote metastatic growth of prostate cancer cells in two xenograft models for human prostate cancer. We have also evaluated the efficacy of Pim-selective inhibitors to antagonize these effects. Results We show here that tumorigenic growth of both subcutaneously and orthotopically inoculated prostate cancer xenografts is enhanced by stable overexpression of either Pim-1 or Pim-3. Moreover, Pim-overexpressing orthotopic prostate tumors are highly invasive and able to migrate not only to the nearby prostate-draining lymph nodes, but also into the lungs to form metastases. When the xenografted mice are daily treated with the Pim-selective inhibitor DHPCC-9, both the volumes as well as the metastatic capacity of the tumors are drastically decreased. Interestingly, the Pim-promoted metastatic growth of the orthotopic xenografts is associated with enhanced angiogenesis and lymphangiogenesis. Furthermore, forced Pim expression also increases phosphorylation of the CXCR4 chemokine receptor, which may enable the tumor cells to migrate towards tissues such as the lungs that express the CXCL12 chemokine ligand. Conclusions Our results indicate that Pim overexpression enhances the invasive properties of prostate cancer cells in vivo. These effects can be reduced by the Pim-selective inhibitor DHPCC-9, which can reach tumor tissues without serious side effects. Thus, Pim-targeting therapies with DHPCC-9-like compounds may help to prevent progression of local prostate carcinomas to fatally metastatic malignancies. PMID:26075720

Hit to lead account of the discovery of a new class of inhibitors of Pim kinases and crystallographic studies revealing an unusual kinase binding mode.

PubMed

Qian, Kevin; Wang, Lian; Cywin, Charles L; Farmer, Bennett T; Hickey, Eugene; Homon, Carol; Jakes, Scott; Kashem, Mohammed A; Lee, George; Leonard, Scott; Li, Jun; Magboo, Ronald; Mao, Wang; Pack, Edward; Peng, Charlene; Prokopowicz, Anthony; Welzel, Morgan; Wolak, John; Morwick, Tina

2009-04-09

A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR. While highly selective within the kinase family, the series shows similar potency for both Pim-1 and Pim-2, which was expected on the basis of homology, but unusual in light of reports in the literature documenting a bias for Pim-1. A rationale for these observations based on Pim-1 and Pim-2 K(M(ATP)) values is suggested. Some interesting cross reactivity with casein kinase-2 was also identified, and structural features which may contribute to the association are discussed.

Pim1 kinase regulates c-Kit gene translation.

PubMed

An, Ningfei; Cen, Bo; Cai, Houjian; Song, Jin H; Kraft, Andrew; Kang, Yubin

2016-01-01

Receptor tyrosine kinase, c-Kit (CD117) plays a pivotal role in the maintenance and expansion of hematopoietic stem/progenitor cells (HSPCs). Additionally, over-expression and/or mutational activation of c-Kit have been implicated in numerous malignant diseases including acute myeloid leukemia. However, the translational regulation of c-Kit expression remains largely unknown. We demonstrated that loss of Pim1 led to specific down-regulation of c-Kit expression in HSPCs of Pim1 -/- mice and Pim1 -/- 2 -/- 3 -/- triple knockout (TKO) mice, and resulted in attenuated ERK and STAT3 signaling in response to stimulation with stem cell factor. Transduction of c-Kit restored the defects in colony forming capacity seen in HSPCs from Pim1 -/- and TKO mice. Pharmacologic inhibition and genetic modification studies using human megakaryoblastic leukemia cells confirmed the regulation of c-Kit expression by Pim1 kinase: i.e., Pim1-specific shRNA knockdown down-regulated the expression of c-Kit whereas overexpression of Pim1 up-regulated the expression of c-Kit. Mechanistically, inhibition or knockout of Pim1 kinase did not affect the transcription of c-Kit gene. Pim1 kinase enhanced c-Kit 35 S methionine labeling and increased the incorporation of c-Kit mRNAs into the polysomes and monosomes, demonstrating that Pim1 kinase regulates c-Kit expression at the translational level. Our study provides the first evidence that Pim1 regulates c-Kit gene translation and has important implications in hematopoietic stem cell transplantation and cancer treatment.

Targeting PIM kinase as a therapeutic strategy in human hepatoblastoma

PubMed Central

Stafman, Laura L.; Mruthyunjayappa, Smitha; Waters, Alicia M.; Garner, Evan F.; Aye, Jamie M.; Stewart, Jerry E.; Yoon, Karina J.; Whelan, Kimberly; Mroczek-Musulman, Elizabeth; Beierle, Elizabeth A.

2018-01-01

Increasing incidence coupled with poor prognosis and treatments that are virtually unchanged over the past 20 years have made the need for the development of novel therapeutics for hepatoblastoma imperative. PIM kinases have been implicated as drivers of tumorigenesis in multiple cancers, including hepatocellular carcinoma. We hypothesized that PIM kinases, specifically PIM3, would play a role in hepatoblastoma tumorigenesis and that PIM kinase inhibition would affect hepatoblastoma in vitro and in vivo. Parameters including cell survival, proliferation, motility, and apoptosis were assessed in human hepatoblastoma cells following PIM3 knockdown with siRNA or treatment with the PIM inhibitor AZD1208. An in vivo model of human hepatoblastoma was utilized to study the effects of PIM inhibition alone and in combination with cisplatin. PIM kinases were found to be present in the human hepatoblastoma cell line, HuH6, and in a human hepatoblastoma patient-derived xenograft, COA67. PIM3 knockdown or inhibition with AZD1208 decreased cell survival, attachment independent growth, and motility. Additionally, inhibition of tumor growth was observed in a hepatoblastoma xenograft model in mice treated with AZD1208. Combination therapy with AZD1208 and cisplatin resulted in a significant increase in animal survival when compared to either treatment alone. The current studies showed that PIM kinase inhibition decreased human hepatoblastoma tumorigenicity both in vitro and in vivo, implying that PIM inhibitors may be useful as a novel therapeutic for children with hepatoblastoma.

PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer.

PubMed

Brasó-Maristany, Fara; Filosto, Simone; Catchpole, Steven; Marlow, Rebecca; Quist, Jelmar; Francesch-Domenech, Erika; Plumb, Darren A; Zakka, Leila; Gazinska, Patrycja; Liccardi, Gianmaria; Meier, Pascal; Gris-Oliver, Albert; Cheang, Maggie Chon U; Perdrix-Rosell, Anna; Shafat, Manar; Noël, Elodie; Patel, Nirmesh; McEachern, Kristen; Scaltriti, Maurizio; Castel, Pau; Noor, Farzana; Buus, Richard; Mathew, Sumi; Watkins, Johnathan; Serra, Violeta; Marra, Pierfrancesco; Grigoriadis, Anita; Tutt, Andrew N

2016-11-01

Triple-negative breast cancers (TNBCs) have poor prognosis and lack targeted therapies. Here we identified increased copy number and expression of the PIM1 proto-oncogene in genomic data sets of patients with TNBC. TNBC cells, but not nonmalignant mammary epithelial cells, were dependent on PIM1 for proliferation and protection from apoptosis. PIM1 knockdown reduced expression of the anti-apoptotic factor BCL2, and dynamic BH3 profiling of apoptotic priming revealed that PIM1 prevents mitochondrial-mediated apoptosis in TNBC cell lines. In TNBC tumors and their cellular models, PIM1 expression was associated with several transcriptional signatures involving the transcription factor MYC, and PIM1 depletion in TNBC cell lines decreased, in a MYC-dependent manner, cell population growth and expression of the MYC target gene MCL1. Treatment with the pan-PIM kinase inhibitor AZD1208 impaired the growth of both cell line and patient-derived xenografts and sensitized them to standard-of-care chemotherapy. This work identifies PIM1 as a malignant-cell-selective target in TNBC and the potential use of PIM1 inhibitors for sensitizing TNBC to chemotherapy-induced apoptotic cell death.

PIM kinases as therapeutic targets against advanced melanoma

PubMed Central

Shannan, Batool; Watters, Andrea; Chen, Quan; Mollin, Stefan; Dörr, Markus; Meggers, Eric; Xu, Xiaowei; Gimotty, Phyllis A.; Perego, Michela; Li, Ling; Benci, Joseph; Krepler, Clemens; Brafford, Patricia; Zhang, Jie; Wei, Zhi; Zhang, Gao; Liu, Qin; Yin, Xiangfan; Nathanson, Katherine L.; Herlyn, Meenhard; Vultur, Adina

2016-01-01

Therapeutic strategies for the treatment of metastatic melanoma show encouraging results in the clinic; however, not all patients respond equally and tumor resistance still poses a challenge. To identify novel therapeutic targets for melanoma, we screened a panel of structurally diverse organometallic inhibitors against human-derived normal and melanoma cells. We observed that a compound that targets PIM kinases (a family of Ser/Thr kinases) preferentially inhibited melanoma cell proliferation, invasion, and viability in adherent and three-dimensional (3D) melanoma models. Assessment of tumor tissue from melanoma patients showed that PIM kinases are expressed in pre- and post-treatment tumors, suggesting PIM kinases as promising targets in the clinic. Using knockdown studies, we showed that PIM1 contributes to melanoma cell proliferation and tumor growth in vivo; however, the presence of PIM2 and PIM3 could also influence the outcome. The inhibition of all PIM isoforms using SGI-1776 (a clinically-available PIM inhibitor) reduced melanoma proliferation and survival in preclinical models of melanoma. This was potentiated in the presence of the BRAF inhibitor PLX4720 and in the presence of PI3K inhibitors. Our findings suggest that PIM inhibitors provide promising additions to the targeted therapies available to melanoma patients. PMID:27448973

EBNA3C Augments Pim-1 Mediated Phosphorylation and Degradation of p21 to Promote B-Cell Proliferation

PubMed Central

Banerjee, Shuvomoy; Lu, Jie; Cai, Qiliang; Sun, Zhiguo; Jha, Hem Chandra; Robertson, Erle S.

2014-01-01

Epstein–Barr virus (EBV), a ubiquitous human herpesvirus, can latently infect the human population. EBV is associated with several types of malignancies originating from lymphoid and epithelial cell types. EBV latent antigen 3C (EBNA3C) is essential for EBV-induced immortalization of B-cells. The Moloney murine leukemia provirus integration site (PIM-1), which encodes an oncogenic serine/threonine kinase, is linked to several cellular functions involving cell survival, proliferation, differentiation, and apoptosis. Notably, enhanced expression of Pim-1 kinase is associated with numerous hematological and non-hematological malignancies. A higher expression level of Pim-1 kinase is associated with EBV infection, suggesting a crucial role for Pim-1 in EBV-induced tumorigenesis. We now demonstrate a molecular mechanism which reveals a direct role for EBNA3C in enhancing Pim-1 expression in EBV-infected primary B-cells. We also showed that EBNA3C is physically associated with Pim-1 through its amino-terminal domain, and also forms a molecular complex in B-cells. EBNA3C can stabilize Pim-1 through abrogation of the proteasome/Ubiquitin pathway. Our results demonstrate that EBNA3C enhances Pim-1 mediated phosphorylation of p21 at the Thr145 residue. EBNA3C also facilitated the nuclear localization of Pim-1, and promoted EBV transformed cell proliferation by altering Pim-1 mediated regulation of the activity of the cell-cycle inhibitor p21/WAF1. Our study demonstrated that EBNA3C significantly induces Pim-1 mediated proteosomal degradation of p21. A significant reduction in cell proliferation of EBV-transformed LCLs was observed upon stable knockdown of Pim-1. This study describes a critical role for the oncoprotein Pim-1 in EBV-mediated oncogenesis, as well as provides novel insights into oncogenic kinase-targeted therapeutic intervention of EBV-associated cancers. PMID:25121590

Metal-conductive polymer hybrid nanostructures: preparation and electrical properties of palladium-polyimidazole nanowires

NASA Astrophysics Data System (ADS)

Al-Hinai, Mariam; Hassanien, Reda; Watson, Scott M. D.; Wright, Nicholas G.; Houlton, Andrew; Horrocks, Benjamin R.

2016-03-01

A simple, convenient method for the formation of hybrid metal/conductive polymer nanostructures is described. Polyimidazole (PIm) has been templated on λ-DNA via oxidative polymerisation of imidazole using FeCl3 to produce conductive PIm/DNA nanowires. The PIm/DNA nanowires were decorated with Pd (Pd/PIm/DNA) by electroless reduction of {{{{PdCl}}}4}2- with NaBH4 in the presence of PIm/DNA; the choice of imidazole was motivated by the potential Pd(II) binding site at the pyridinic N atom. The formation of PIm/DNA and the presence of metallic Pd on Pd/PIm/DNA nanowires were verified by FTIR, UV-vis and XPS spectroscopy techniques. AFM studies show that the nanowires have diameters in the range 5-45 nm with a slightly greater mean diameter (17.1 ± 0.75 nm) for the Pd-decorated nanowires than the PIm/DNA nanowires (14.5 ± 0.89 nm). After incubation for 24 h in the polymerisation solution, the PIm/DNA nanowires show a smooth, uniform morphology, which is retained after decoration with Pd. Using a combination of scanned conductance microscopy, conductive AFM and two-terminal measurements we show that both types of nanowire are conductive and that it is possible to discriminate different possible mechanisms of transport. The conductivity of the Pd/PIm/DNA nanowires, (0.1-1.4 S cm-1), is comparable to the PIm/DNA nanowires (0.37 ± 0.029 S cm-1). In addition, the conductance of Pd/PIm/DNA nanowires exhibits Arrhenius behaviour (E a = 0.43 ± 0.02 eV) as a function of temperature in contrast to simple Pd/DNA nanowires. These results indicate that although the Pd crystallites on Pd/PIm/DNA nanowires decorate the PIm polymer, the major current pathway is through the polymer rather than the Pd.

The influence of superimposed DC current on electrical and spectroscopic characteristics of HiPIMS discharge

NASA Astrophysics Data System (ADS)

Zuo, Xiao; Chen, Rende; Liu, Jingzhou; Ke, Peiling; Wang, Aiying

2018-01-01

The electrical characteristics and spectroscopic properties have been comprehensively investigated in a DC superimposed high power impulse magnetron sputtering (DC-HiPIMS) deposition system in this paper. The influence of superimposed DC current on the variation of target and substrate current waveforms, active species and electron temperatures with pulse voltages are focused. The peak target currents in DC-HiPIMS are lower than in HiPIMS. The time scales of the two main discharge processes like ionization and gas rarefaction in DC-HiPIMS are analyzed. When the pulse voltage is higher than 600 V, the gas rarefaction effect becomes apparent. Overall, the ionization process is found to be dominant in the initial ˜100 μs during each pulse. The active species of Ar and Cr in DC-HiPIMS are higher than in HiPIMS unless that the pulse voltage reaches 900 V. However, the ionization degree in HiPIMS exceeds that in DC-HiPIMS at around 600 V. The electron temperature calculated by modified Boltzmann plot method based on corona model has a precipitous increase from 0.87 to 25.0 eV in HiPIMS, but varies mildly after the introduction of the superimposed DC current. Additionally, the current from plasma flowing to the substrate is improved when a DC current is superimposed with HiPIMS.

Peri-implant bone formation and surface characteristics of rough surface zirconia implants manufactured by powder injection molding technique in rabbit tibiae.

PubMed

Park, Young-Seok; Chung, Shin-Hye; Shon, Won-Jun

2013-05-01

To evaluate osseointegration in rabbit tibiae and to investigate surface characteristics of novel zirconia implants made by powder injection molding (PIM) technique, using molds with and without roughened inner surfaces. A total of 20 rabbits received three types of external hex implants with identical geometry on the tibiae: machined titanium implants, PIM zirconia implants without mold etching, and PIM zirconia implants with mold etching. Surface characteristics of the three types of implant were evaluated. Removal torque tests and histomorphometric analyses were performed. The roughness of PIM zirconia implants was higher than that of machined titanium implants. The PIM zirconia implants exhibited significantly higher bone-implant contact and removal torque values than the machined titanium implants (P < 0.001). The PIM zirconia implants using roughened mold showed significantly higher removal torque values than PIM zirconia implants without using roughened mold (P < 0.001). It is concluded that the osseointegration of PIM zirconia implant is promising and PIM using roughened mold etching technique can produce substantially rough surfaces on zirconia implants. © 2012 John Wiley & Sons A/S.

The PIM kinases in hematological cancers.

PubMed

Alvarado, Yesid; Giles, Francis J; Swords, Ronan T

2012-02-01

The PIM genes represent a family of proto-oncogenes that encode three different serine/threonine protein kinases (PIM1, PIM2 and PIM3) with essential roles in the regulation of signal transduction cascades, which promote cell survival, proliferation and drug resistance. PIM kinases are overexpressed in several hematopoietic tumors and support in vitro and in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. PIM kinases do not have an identified regulatory domain, which means that these proteins are constitutively active once transcribed. They appear to be critical downstream effectors of important oncoproteins and, when overexpressed, can mediate drug resistance to available agents, such as rapamycin. Recent crystallography studies reveal that, unlike other kinases, they possess a hinge region, which creates a unique binding pocket for ATP, offering a target for an increasing number of potent small-molecule PIM kinase inhibitors. Preclinical studies in models of various hematologic cancers indicate that these novel agents show promising activity and some of them are currently being evaluated in a clinical setting. In this review, we profile the PIM kinases as targets for therapeutics in hematologic malignancies.

Characterization of graded TiC layers deposited by HiPIMS method

NASA Astrophysics Data System (ADS)

Bohovicova, Jana; Bonova, Lucia; Halanda, Juraj; Ivan, Jozef; Mesko, Marcel; Advanced Technologies Research Institute Team; Institute of Electronic; Photonic Team

2016-09-01

An advanced yet recent development of sputter technique is high power impulse magnetron sputtering (HiPIMS), in which short, energetic pulses are applied to the target, leading to a formation of an ultra-dense plasma in front of the cathode, that provide a high degree of ionization of sputtered material, and consequently enable to control the energy and the direction of the deposition flux. This gives a possibility to alter composition and microstructure in a controlled manner, enables the optimization of TiC for tribological applications. The aim of this work is to link physical phenomena in transient HiPIMS discharges to microstructural and compositional properties of graded TiC thin films. It was found that Ti bottom layer is contamination free. Compared to the direct current magnetron sputtering films, we observed an element specific reduction of impurities measured by ERDA by a factor 3 for N, 4 for H and by a factor of 20 for O. The high purity of Ti layer is partly explained by gas rarefaction and the cleaning effect of the bombarding ions. Graphitization degree of carbon top layer was elucidated by Raman spectroscopy. The compositional effects are correlated with differences in the film microstructure revealed by SEM, XRD and TEM analysis. This work was supported by VEGA, Project No. 1/0503/15 and APVV, Project No. 15-0168.

Paladin Integrated Management (PIM)

DTIC Science & Technology

2015-12-01

Strategy and Net- Centric Services Strategy, and the principles and rules identified in the DoD lEA, excepting tactical and non-IP communications 3...with Net-Centric Data Strategy and Net- Centric Services Strategy, and the principles and rules identified in the DoD lEA, excepting tactical and...effective information exchanges 2) Compliant with Net-Centric Data Strategy and Net-Centric Services Strategy, and the principles and rules

Potentially inappropriate medications in geriatric outpatients with polypharmacy: application of six sets of published explicit criteria

PubMed Central

Chang, Chirn-Bin; Chen, Jen-Hau; Wen, Chiung-Jung; Kuo, Hsu-Ko; Lu, I-Shu; Chiu, Lee-Shu; Wu, Shwu-Chong; Chan, Ding-Cheng (Derrick)

2011-01-01

AIM Our aim was to compare the practicability of six different potentially inappropriate medication (PIM) criteria in geriatric outpatients with polypharmacy. METHODS We analysed baseline data from the Medication Safety Review Clinic in Taiwanese Elders (MSRC-Taiwan) study. The prevalence and correlates of PIMs were determined on the basis of criteria developed in the USA, Canada, France, Norway, Ireland and Thailand. The percentage of PIMs considered as drug-related problems and the problem-solving rate are reported. RESULTS In the 193 participants, the prevalence of PIM varied from 24 to 73%. Application of the criteria revealed that a high number of chronic medications was a common risk factor for having at least one PIM. Of the 1713 medications reviewed, 5.6–14.8% were considered PIMs. Only 30–40% of the identified PIMs were reported as drug-related problems by the MSRC team experts. Criteria with a higher number of statements and a higher percentage of local market/institution drug availability tended to detect more PIMs. CONCLUSIONS The prevalence of PIM varied significantly when different criteria were applied. Caution should be exercised in applying PIM criteria developed in other regions when medication availability in the local market is limited. PMID:21557760

Proceedings of the 26th Project Integration Meeting

NASA Technical Reports Server (NTRS)

1986-01-01

Progress made by the Flat-plate Solar Array (FSA) Project is described for the period July 1985 to April 1986. Included are reports on silicon sheet growth and characterization, silicon material, process development, high-efficienty cells, environmental isolation, engineering sciences, and reliability physics. Also included are technical and plenary presentations made at the 26th Project Integration Meeting (PIM) held on April 29 to 30 and May 1, 1986.

Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NF-kappaB pathway.

PubMed

Ren, Ke; Zhang, Wei; Shi, Yujun; Gong, Jianping

2010-06-01

Pim-2 is proved to be relevant to the tumorigenesis of hepatocellular carcinoma (HCC), but the mechanism is unclear. We studied the relationship among Pim-2, NF-kappaB and API-5. In our experiment, expression level of the three factors and phosphorylation level of API-5, as well as NF-kappaB activity, were detected in HCC tissues and the nontumorous controls. Then Pim-2 gene was transfected into nontumorous liver cells L02, and Pim-2 SiRNA was transfected into hepatoblastoma cell line HepG2. Parthenolide was added as NF-kappaB inhibitor. The same detections as above were repeated in the cells, along with the apoptosis analysis. We found the levels of Pim-2, NF-kappaB and API-5, as well as NF-kappaB activity, were significantly higher in HCC tissues. Pim-2 level was increased in L02 cells after the transfection of Pim-2 gene, but decreased in HepG2 cells after the transfection of Pim-2 SiRNA. The levels of NF-kappaB and API-5, as well as NF-kappaB activity and API-5 phosphorylation level, were in accordance with Pim-2 level, but could be reversed by Parthenolide. Cell apoptosis rates were negatively correlated with API-5 phosphorylation level. Therefore, we infer that Pim-2 could activate API-5 to inhibit the apoptosis of liver cells, and NF-kappaB is the key regulator.

Knockdown of Pim-3 suppresses the tumorigenicity of glioblastoma by regulating cell cycle and apoptosis.

PubMed

Quan, J; Zhou, L; Qu, J

2015-03-09

Products of the Pim (the proviral integration site for the Moloney murine leukemia virus) family of proto—oncogenes possess serine/threonine kinase activity and belong to the Ca2+/calmodulin—dependent protein kinase group. Pim—3, a member of the Pim family is closely linked to the development of a variety of tumors. However, the role of Pim—3 in human glioblastoma remains unknown. In this study, we elucidated the role of Pim—3 in the growth and apoptosis of glioblastoma cells. Western blotting was used for determination of protein levels, and shRNA was used for Pim—3 knockdown. The MTT assay was used to evaluate cell proliferation and flow cytometry was used to determine cell cycle status and the number of apoptotic cells. A mouse xenograft model was established by injecting nude mice with Pim—3—depleted glioblastoma cells in order to determine tumor growth in vivo. We demonstrated that Pim—3 was highly expressed in human glioblastoma cell lines. We also found that knockdown of Pim—3 by specific shRNA slowed decreased proliferation, induced cell cycle arrest in the G0/G1 phase, and increased apoptosis in glioblastoma cells. Pim—3 knockdown potently inhibited the growth of subcutaneously implanted glioblastoma cells in vivo. We further revealed that Pim—3 knockdown induced growth inhibition by reducing the levels of the anti—apoptotic protein Bcl—xl and cell cycle regulatory proteins, including cyclin D1 and Cdc25C, and increasing the levels of the pro—apoptotic protein Bax.

Risk Factors for Initiation of Potentially Inappropriate Medications in Community-Dwelling Older Adults with and without Alzheimer's Disease.

PubMed

Hyttinen, Virva; Taipale, Heidi; Tanskanen, Antti; Tiihonen, Jari; Tolppanen, Anna-Maija; Hartikainen, Sirpa; Valtonen, Hannu

2017-01-01

Various criteria have been created to define potentially inappropriate medications (PIMs) to help improve the quality and safety of medicine use in older patients. Individuals with Alzheimer's disease (AD) may be at higher risk of adverse drug events associated with PIMs (such as falls). Our objective was to determine the risk factors for PIM initiation in a nationwide cohort of community dwellers aged ≥65 years with and without AD. The Finnish nationwide MEDALZ cohort includes all patients diagnosed with AD in 2005-2011 (n = 70,718) and two comparison individuals without AD (non-AD) matched for age, sex and region of residence for each person with AD. After a 1-year washout period for PIM use and exclusion of those aged <65 years, we included 50,494 patients with AD and 106,306 comparison subjects. PIM use was defined according to Finnish criteria. Subjects without AD initiated PIMs more frequently than those with AD (16.4 vs. 12.2%, respectively; p < 0.001). The most common PIMs were muscle relaxants and urinary antispasmodics. Older individuals (aged ≥75 years) were less likely to initiate PIMs. In the AD group, women were less likely to initiate PIMs than men. More comorbidities were associated with PIM initiation, especially in the non-AD group. The use of opioids or psychotropic medicines was associated with PIM initiation in both cohorts. Regional differences between university hospital districts were observed. PIM initiation was dependent on patient characteristics and possibly also some healthcare system-related factors such as differing regional treatment practices. It is important that medicines prescribed to the older vulnerable population are assessed regularly to avoid adverse effects and ensure safe pharmacotherapy, especially in those with multiple comorbidities.

Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine

PubMed Central

Xu, Dapeng; Cobb, Michael G.; Gavilano, Lily; Witherspoon, Sam M.; Williams, Daniel; White, Catherine D.; Taverna, Pietro; Bednarski, Brian K.; Kim, Hong Jin; Baldwin, Albert S.; Baines, Antonio T.

2013-01-01

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a 5-year survival rate of only 6%. Although the cytosine analog gemcitabine is the drug commonly used to treat PDAC, chemoresistance unfortunately renders the drug ineffective. Thus, strategies that can decrease this resistance will be essential for improving the dismal outcome of patients suffering from this disease. We previously observed that oncogenic Pim-1 kinase was aberrantly expressed in PDAC tissues and cell lines and was responsible for radioresistance. Furthermore, members of the Pim family have been shown to reduce the efficacy of chemotherapeutic drugs in cancer. Therefore, we attempted to evaluate the role of Pim-3 in chemoresistance of PDAC cells. We were able to confirm upregulation of the Pim-3 oncogene in PDAC tissues and cell lines vs. normal samples. Biological consequences of inhibiting Pim-3 expression with shRNA-mediated suppression included decreases in anchorage-dependent growth, invasion through Matrigel and chemoresistance to gemcitabine as measured by caspase-3 activity. Additionally, we were able to demonstrate that Pim-1 and Pim-3 play overlapping but non-identical roles as it relates to gemcitabine sensitivity of pancreatic cancer cells. To further support the role of Pim-3 suppression in sensitizing PDAC cells to gemcitabine, we used the pharmacological Pim kinase inhibitor SGI-1776. Treatment of PDAC cells with SGI-1776 resulted in decreased phosphorylation of the proapoptotic protein Bad and cell cycle changes. When SGI-1776 was combined with gemcitabine, there was a greater decrease in cell viability in the PDAC cells vs. cells treated with either of the drugs separately. These results suggest combining drug therapies that inhibit Pim kinases, such as Pim-3, with chemotherapeutic agents, to aid in decreasing chemoresistance in pancreatic cancer. PMID:23760491

Novel Therapeutic Approaches Toward Treating Prostate Cancer

DTIC Science & Technology

2012-05-01

Pim-1 activity is identified as essential in the feedback regulation of RTK levels by AKT inhibition. Pim-1 appears to control RTKs by regulating...AKT and Pim inhibitors provide synergistic inhibition of tumor growth. Thus, this combination therapy has the potential activity to be developed as a...laboratory has developed novel benzylidene thiazolidine-2,4 diones, (D5, SMI-4a) that inhibit the activity of Pim kinase. These agents reverse Pim

Pim-2 protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced apoptosis via downregulation of Bim expression.

PubMed

Xu, Yan; Xing, Yawei; Xu, Yanjie; Huang, Chahua; Bao, Huihui; Hong, Kui; Cheng, Xiaoshu

2016-12-01

We know that silencing Bim, a pro-apoptosis protein, significantly attenuates glucose and oxygen-deprived induced apoptosis in cardiomyocytes. However, the mechanisms underlying the regulation of the Bim activation in the heart have remained unknown. Pim-2 is one of three Pim serine/threonine kinase family members thought to be involved in cell survival and proliferation. H9c2 cardiomyocytes were subjected to a hypoxia/reoxygenation (H/R) condition in vitro, mimicking ischemic/reperfusion injury in vivo. H/R augmented the expression of Bim, Cyt C, and Pim-2 and induced H9c2 cell apoptosis. Overexpression of Pim-2 attenuated apoptosis which induced by H/R in H9c2 cells, via downregulation of Bim and Cyt C expression. Silencing of Pim-2 promoted H/R-induced apoptosis via upregulation of Bim and Cyt C expression. Co-IP revealed the interaction between Pim-2 and Bim protein, with Bim Ser 65 phosphorylated by Pim-2. Furthermore, blocking proteasome activity by MG132 prevented Bim degradation, and Bim S65A mutation could reverse the anti-apoptotic role of Pim-2 which induced by H/R. These data demonstrated that Pim-2 is a novel Bim-interacting protein, which negatively regulates Bim degradation and protects H9c2 cardiomyocytes from H/R-induced apoptosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776

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

Hou, Xiuxiu, E-mail: show-1989@163.com; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000; Yu, Yunfang, E-mail: yyf_8247425@163.com

Provirus integration site for Moloney murine leukemia virus 1 (Pim-1) has proved to be an oncogene and it is known that to depress Pim-1 activity may be a novel oncological treatment strategy. SGI-1776, a small molecule, is the first clinically tested inhibitor of the Pim kinase family. Here, we aimed to explore the effect of SGI-1776 on salivary adenoid cystic carcinoma (SACC). Expression of Pim-1 was confirmed in SACC and control tissues by qRT-PCR. After SGI-1776 treatment, the Pim-1 expressions and Pim-1 kinase activity in both SACC-83 and SACC-LM cell lines were measured. Cell proliferation, cell invasion, cell cycle, apoptosismore » and mitochondrial membrane potential were analyzed. Also, the expression of FOXO3a, p-FOXO3a, RUNX3, Bcl-2, BAD, p-BAD, Bim and p-Bim were detected by Western blot. The results showed that Pim-1 was significantly overexpressed in SACC tissues. SGI-1776 down-regulated the Pim-1 expression, inhibited Pim-1 kinase activity, reduced cell proliferation, decreased invasive ability, increased caspase-3 activity and induced apoptosis, cell cycle arrest and mitochondrial depolarization. Reduced expression was also seen in p-FOXO3a, RUNX3, Bcl-2, p-BAD and p-Bim, whereas no significant changes were observed from FOXO3a, BAD and Bim. These results confirm the pivotal role of Pim-1 in SACC and suggest that targeting Pim-1 kinase signal pathway by SGI-1776 might be a promising therapeutic modality for SACC.« less

Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776.

PubMed

Hou, Xiuxiu; Yu, Yunfang; Feng, Jianguo; Wang, Jiafeng; Zheng, Chuanming; Ling, Zhiqiang; Ge, Minghua; Zhu, Xin

2017-03-15

Provirus integration site for Moloney murine leukemia virus 1 (Pim-1) has proved to be an oncogene and it is known that to depress Pim-1 activity may be a novel oncological treatment strategy. SGI-1776, a small molecule, is the first clinically tested inhibitor of the Pim kinase family. Here, we aimed to explore the effect of SGI-1776 on salivary adenoid cystic carcinoma (SACC). Expression of Pim-1 was confirmed in SACC and control tissues by qRT-PCR. After SGI-1776 treatment, the Pim-1 expressions and Pim-1 kinase activity in both SACC-83 and SACC-LM cell lines were measured. Cell proliferation, cell invasion, cell cycle, apoptosis and mitochondrial membrane potential were analyzed. Also, the expression of FOXO3a, p-FOXO3a, RUNX3, Bcl-2, BAD, p-BAD, Bim and p-Bim were detected by Western blot. The results showed that Pim-1 was significantly overexpressed in SACC tissues. SGI-1776 down-regulated the Pim-1 expression, inhibited Pim-1 kinase activity, reduced cell proliferation, decreased invasive ability, increased caspase-3 activity and induced apoptosis, cell cycle arrest and mitochondrial depolarization. Reduced expression was also seen in p-FOXO3a, RUNX3, Bcl-2, p-BAD and p-Bim, whereas no significant changes were observed from FOXO3a, BAD and Bim. These results confirm the pivotal role of Pim-1 in SACC and suggest that targeting Pim-1 kinase signal pathway by SGI-1776 might be a promising therapeutic modality for SACC. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Defining the interaction of human soluble lectin ZG16p and mycobacterial phosphatidylinositol mannosides

PubMed Central

Ikeda, Akemi; Kojima-Aikawa, Kyoko; Taniguchi, Naoyuki; Varón Silva, Daniel; Feizi, Ten; Seeberger, Peter H.; Yamaguchi, Yoshiki

2018-01-01

ZG16p is a soluble mammalian lectin that interacts with mannose and heparan sulfate. Here we describe detailed analyses of the interactions of human ZG16p with mycobacterial phosphatidylinositol mannosides (PIMs), using glycan microarray and NMR. Pathogen-related glycan microarray analysis identified phosphatidylinositol mono- and di-mannosides (PIM1 and PIM2) as novel ligand candidates of ZG16p. Saturation Transfer Difference (STD) NMR and transferred NOE experiments with chemically synthesized PIM glycans indicate that PIMs preferentially interacts with ZG16p using the mannose residues. Binding site of PIMs is identified by chemical shift perturbation experiments using uniformly 15N-labeled ZG16p. NMR results with docking simulations suggest a binding mode of ZG16p and PIM glycan, which would help to consider the physiological role of ZG16p. PMID:25919894

Immunological characterization of pulmonary intravascular macrophages

NASA Technical Reports Server (NTRS)

Chitko-McKown, C. G.; Reddy, D. N.; Chapes, S. K.; McKown, R. D.; Blecha, F.; Spooner, B. S. (Principal Investigator)

1992-01-01

Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.

Synthesis and biological investigation of PIM mimics carrying biotin or a fluorescent label for cellular imaging.

PubMed

Front, Sophie; Bourigault, Marie-Laure; Rose, Stéphanie; Noria, Ségueni; Quesniaux, Valérie F J; Martin, Olivier R

2013-01-16

Phosphatidyl inositol mannosides (PIMs) are constituents of the mycobacterial cell wall; these glycolipids are known to exhibit potent inhibitory activity toward the LPS-induced production of cytokines by macrophages, and therefore have potential as anti-inflammatory agents. Recently, heterocyclic analogues of PIMs in which the inositol is replaced by a piperidine (aza-PIM mimics) or a tetrahydropyran moiety (oxa-PIM mimics) have been prepared by short synthetic sequences and shown to retain the biological activity of the parent PIM structures. In this investigation, the aza-PIM analogue was used as a convenient scaffold to link biotin or a fluorescent label (tetramethyl-rhodamine) by way of an aminocaproyl spacer, with the goal of using these conjugates for intracellular localization and for the study of the mechanism of their antiinflammatory action. The synthesis of these compounds is reported, as well as the evaluation of their activities as inhibitors of LPS-induced cytokine production by macrophages (TNFα, IL12p40); preliminary investigations by FACS and confocal microscopy indicated that PIM-biotin conjugate binds to macrophage membranes with rapid kinetics.

The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition.

PubMed

Mologni, Luca; Magistroni, Vera; Casuscelli, Francesco; Montemartini, Marisa; Gambacorti-Passerini, Carlo

2017-01-01

PIM1 is over-expressed in multiple tumors, including prostate cancer (PCa). PIM1 upregulation is mediated by direct binding of the ERG transcription factor to its promoter. About 50% of PCa cases are characterized by the presence of the TMPRSS2/ERG fusion, leading to ERG over-expression and thus to PIM1 transcriptional activation. PIM kinases are considered as weak oncogenes, but when combined with additional genetic alterations can induce strong transforming effects. Here we show anti-proliferative activity of the newly described PIM1 inhibitor NMS-P645 in combination with the PI3K inhibitor GDC-0941 in TMPRSS2/ERG positive and negative PCa cells. Treatment with NMS-P645 alone can reverse PIM1-mediated pro-survival signals in prostate cells, such as activation of STAT3 through Tyr705 phosphorylation and resistance to taxane-based treatments, but does not exert a strong anti-tumoral effect. However, the simultaneous treatment with NMS-P645 and GDC-0941 induces a significant anti-proliferative response in PCa cells. These results support the use of combination strategies with PIM and PI3K inhibitors as effective treatment for PCa cases.

CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis

PubMed Central

Huot, Geneviève; Vernier, Mathieu; Bourdeau, Véronique; Doucet, Laurent; Saint-Germain, Emmanuelle; Gaumont-Leclerc, Marie-France; Moro, Alejandro; Ferbeyre, Gerardo

2014-01-01

The expression of the forkhead transcription factor checkpoint suppressor 1 (CHES1), also known as FOXN3, is reduced in many types of cancers. We show here that CHES1 decreases protein synthesis and cell proliferation in tumor cell lines but not in normal fibroblasts. Conversely, short hairpin RNA–mediated depletion of CHES1 increases tumor cell proliferation. Growth suppression depends on the CHES1 forkhead DNA-binding domain and correlates with the nuclear localization of CHES1. CHES1 represses the expression of multiple genes, including the kinases PIM2 and DYRK3, which regulate protein biosynthesis, and a number of genes in cilium biogenesis. CHES1 binds directly to the promoter of PIM2, and in cells expressing CHES1 the levels of PIM2 are reduced, as well as the phosphorylation of the PIM2 target 4EBP1. Overexpression of PIM2 or eIF4E partially reverses the antiproliferative effect of CHES1, indicating that PIM2 and protein biosynthesis are important targets of the antiproliferative effect of CHES1. In several human hematopoietic cancers, CHES1 and PIM2 expressions are inversely correlated, suggesting that repression of PIM2 by CHES1 is clinically relevant. PMID:24403608

CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis.

PubMed

Huot, Geneviève; Vernier, Mathieu; Bourdeau, Véronique; Doucet, Laurent; Saint-Germain, Emmanuelle; Gaumont-Leclerc, Marie-France; Moro, Alejandro; Ferbeyre, Gerardo

2014-03-01

The expression of the forkhead transcription factor checkpoint suppressor 1 (CHES1), also known as FOXN3, is reduced in many types of cancers. We show here that CHES1 decreases protein synthesis and cell proliferation in tumor cell lines but not in normal fibroblasts. Conversely, short hairpin RNA-mediated depletion of CHES1 increases tumor cell proliferation. Growth suppression depends on the CHES1 forkhead DNA-binding domain and correlates with the nuclear localization of CHES1. CHES1 represses the expression of multiple genes, including the kinases PIM2 and DYRK3, which regulate protein biosynthesis, and a number of genes in cilium biogenesis. CHES1 binds directly to the promoter of PIM2, and in cells expressing CHES1 the levels of PIM2 are reduced, as well as the phosphorylation of the PIM2 target 4EBP1. Overexpression of PIM2 or eIF4E partially reverses the antiproliferative effect of CHES1, indicating that PIM2 and protein biosynthesis are important targets of the antiproliferative effect of CHES1. In several human hematopoietic cancers, CHES1 and PIM2 expressions are inversely correlated, suggesting that repression of PIM2 by CHES1 is clinically relevant.

3D-QSAR and virtual screening studies of thiazolidine-2,4-dione analogs: Validation of experimental inhibitory potencies towards PIM-1 kinase

NASA Astrophysics Data System (ADS)

Asati, Vivek; Bharti, Sanjay Kumar; Budhwani, Ashok Kumar

2017-04-01

The proviral insertion site in moloney murine leukemia virus (PIM) is a family of serine/threonine kinase of Ca2+-calmodulin-dependent protein kinase (CAMK) group which is responsible for the activation and regulation of cellular transcription and translation. The three isoforms of PIM kinase (PIM-1, PIM-2 and PIM-3) share high homology and functional idleness are widely expressed and involved in a variety of biological processes including cell survival, proliferation, differentiation and apoptosis. Altered expression of PIM-1 kinase correlated with hematologic malignancies and solid tumors. In the present study, atom-based 3D-QSAR, docking and virtual screening studies have been performed on a series of thiazolidine-2,4-dione derivatives as PIM-1 kinase inhibitors. 3D-QSAR and docking approach has shortlisted the most active thiazolidine-2,4-dione derivatives such as 28, 31, 33 and 35 with the incorporation of more than one structural feature in a single molecule. External validations by various parameters and molecular docking studies at the active site of PIM-1 kinase have proved the reliability of the developed 3D-QSAR model. The generated pharmacophore (AADHR.33) from 3D-QSAR study was used for screening of drug like compounds from ZINC database, where ZINC15056464 and ZINC83292944 showed potential binding affinities at the active site amino acid residues (LYS67, GLU171, ASP128 and ASP186) of PIM-1 kinase.

Impact of an Innovative Educational Strategy on Medication Appropriate Use and Length of Stay in Elderly Patients

PubMed Central

Corbi, Graziamaria; Gambassi, Giovanni; Pagano, Gennaro; Russomanno, Giusy; Conti, Valeria; Rengo, Giuseppe; Leosco, Dario; Bernabei, Roberto; Filippelli, Amelia; Ferrara, Nicola

2015-01-01

Abstract To evaluate the impact of an educational strategy on potentially inappropriate medications (PIMs) and length of stay in hospitalized elderly patients. Design: An open study, with two cross-sectional surveys interspersed with an educational program (PRE phase and POST phase), has been performed in order to compare the PIMs number before and after the introduction of an educational strategy. The study included 2 phases: PRE, in which patients were enrolled as control group; POST, in which an educational strategy on the PIMs use was introduced among physicians, and patients were enrolled as intervention group. Setting: Italian residential rehabilitation Centre. Inclusion criteria were ≥2 active chronic diseases and the current use of ≥4 medications. The educational strategy consisted of a 3-day course on strategies to prevent PIMs and a computerized tool running on a Personal Digital Assistant (PDA) device to check for PIMs. Outcomes: The primary was the PIMs number, the secondary the length of stay. Results: A total of 790 patients, 450 controls and 340 cases, were enrolled. According to the Beers criteria, 52.3% of the study population received ≥1 PIMs, 18.73% ≥2, and 2.4% ≥4 PIMs. A significant reduction of PIMs (P = 0.020) and length of stay (P < 0.0001) were seen in the intervention group. At multivariate analysis, PIMs significantly correlated with age, drugs number, and the intervention, and the length of stay significantly correlated with disease count, comorbidities, and intervention. These data suggest that our educative instrument may be useful in reducing the PIMs number and length of hospitalization in elderly with a high number of drugs and comorbidities. PMID:26091456

Correlation of Incident Potentially Inappropriate Medication Prescriptions and Hospitalization: An Analysis Based on the PRISCUS List.

PubMed

Henschel, Frank; Redaelli, Marcus; Siegel, Martin; Stock, Stephanie

2015-09-01

Multimorbidity and polypharmacy represent a major problem for elderly patients. Potentially inappropriate medication (PIM) use is highly prevalent among the elderly. PIMs are considered high-risk drugs and are suspected to be responsible for adverse drug events (ADEs) leading to hospitalization. The objective of this study was to determine hospitalization rates related to selected ADEs in elderly patients with an incident prescription of a PIM as defined by the PRISCUS list. A second objective was to identify other factors independently associated with hospitalization. We retrospectively analysed a full census of pharmaceutical claims, from one of the largest public sickness funds in Germany, for 647,073 patients aged ≥65 years in 2010, the year of publication of the PRISCUS list. Patients who received an incident PIM in 2010 were assigned to the intervention group. Propensity score matching was used to build a control group of patients at a comparable risk level who received an incident equivalent non-PIM. The risk of hospitalization due to PIM prescription was estimated via the odds ratio (OR). Risk factors were analysed via logistic regression models. The results showed significantly more ADEs in the PIM group. The OR for hospitalization was 1.54 [95 % confidence interval (CI) 1.23-1.93] for patients receiving any PIM compared with those who received a non-PIM. This trend remained stable [OR 1.46 (95 % CI 1.16-1.84)] after adjustment for relevant covariates in the logistic regression models showing ORs for each risk factor. Besides PIMs, common risk factors such as greater age, comorbidity and specific drug classes were significantly responsible for hospitalization. PIMs (as defined by the PRISCUS list) are associated with high rates of ADEs associated with hospitalization. Our study suggests that PIM reduction may result in a lower risk of hospitalization in the elderly.

Pim-1L Protects Cell Surface-Resident ABCA1 From Lysosomal Degradation in Hepatocytes and Thereby Regulates Plasma High-Density Lipoprotein Level.

PubMed

Katsube, Akira; Hayashi, Hisamitsu; Kusuhara, Hiroyuki

2016-12-01

ATP-binding cassette transporter A1 (ABCA1) exerts an atheroprotective action through the biogenesis of high-density lipoprotein in hepatocytes and prevents the formation of foam cells from macrophages. Controlling ABCA1 is a rational approach to improving atherosclerotic cardiovascular disease. Although much is known about the regulatory mechanism of ABCA1 synthesis, the molecular mechanism underpinning its degradation remains to be clearly described. ABCA1 possesses potential sites of phosphorylation by serine/threonine-protein kinase Pim-1 (Pim-1). Pim-1 depletion decreased the expression of cell surface-resident ABCA1 (csABCA1) and apolipoprotein A-I-mediated [ 3 H]cholesterol efflux in the human hepatoma cell line HepG2, but not in peritoneal macrophages from mice. In vitro kinase assay, immunoprecipitation, and immunocytochemistry suggested phosphorylation of csABCA1 by the long form of Pim-1 (Pim-1L). Cell surface biotinylation indicated that Pim-1L inhibited lysosomal degradation of csABCA1 involving the liver X receptor β, which interacts with csABCA1 and thereby protects it from ubiquitination and subsequent lysosomal degradation. Cell surface coimmunoprecipitation with COS-1 cells expressing extracellularly hemagglutinin-tagged ABCA1 showed that Pim-1L-mediated phosphorylation of csABCA1 facilitated the interaction between csABCA1 and liver X receptor β and thereby stabilized the csABCA1-Pim-1L complex. Mice deficient in Pim-1 kinase activity showed lower expression of ABCA1 in liver plasma membranes and lower plasma high-density lipoprotein levels than control mice. Pim-1L protects hepatic csABCA1 from lysosomal degradation by facilitating the physical interaction between csABCA1 and liver X receptor β and subsequent stabilization of the csABCA1-Pim-1L complex and thereby regulates the circulating level of high-density lipoprotein. Our findings may aid the development of high-density lipoprotein-targeted therapy. © 2016 American Heart Association, Inc.

Pim-3 contributes to radioresistance through regulation of the cell cycle and DNA damage repair in pancreatic cancer cells

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

Chen, Xiang-Yuan; Wang, Zhen; Li, Bei

Resistance of cancer cells to chemoradiotherapy is a major clinical problem in pancreatic cancer treatment. Therefore, understanding the molecular basis of cellular resistance and identifying novel targets are essential for improving treatment efficacy for pancreatic cancer patients. Previous studies have demonstrated a significant role for Pim-3 in pancreatic cancer survival against gemcitabine-induced genotoxic stress. Here, we observed that radiation treatment enhanced Pim-3 expression in human pancreatic cancer cells in vitro. Stable overexpression of Pim-3 in pancreatic cancer cells significantly protected cells against radiation treatment by attenuating G2/M phase cell cycle arrest and DNA damage response. Silencing of Pim-3 expression significantly elevatedmore » the phosphorylation of histone variant H2AX, a marker of DNA double strand breaks, and decreased the activation of ataxia-telangiectasia-mutated (ATM) kinase, along with its downstream targets, eventually enhancing the radiosensitivity of human pancreatic cancer cells in vitro and in vivo. Hence, we demonstrated a novel function for Pim-3 in human pancreatic cancer cell survival against radiation. Targeting Pim-3 may be a promising way to improve treatment efficacy in combination with radiotherapy in human pancreatic cancer. - Highlights: • This is first study to demonstrate that Pim-3 is endogenously induced by ionizing radiation in pancreatic cancer cells, and Pim-3 overexpression enhanced radioresistance of pancreatic cancer cells both in vitro and in vivo. • This is first study to provide evidence that radioresistance induced by Pim-3 is mainly attributed to Pim-3 induces activation of ATM, which subsequently activates checkpoint 1, leading to amplification of DNA repair through cell cycle arrest and DNA repair pathways. • This is first study to indicate that targeting Pim-3 may be a promising strategy to provide better treatment efficacy in combination with radiotherapy in human pancreatic cancer.« less

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

Amson, R.; Przedborski, S.; Telerman, A.

The authors measured the human pim-1 protooncogene (PIM) expression during fetal development and in hematopoietic malignancies. The data indicate that during human fetal hematopoiesis the 33-kDa pim product, p33pim, is highly expressed in the liver and the spleen. In contrast, a the adult stage it is only slightly expressed in circulating granulocytes. Out of 70 hematopoietic malignancies analyzed, 51 patients and 19 cell lines, p33pim was overexpressed in {approx} 30% of the samples, particularly in myeloid and lymphoid acute leukemias. This overexpression was unrelated to any stage of cellular differentiation and was not due to gene rearrangement or amplification. Thesemore » results imply a physiological role of the pim-1 protooncogene during hematopoietic development and a deregulation in various leukemias.« less

Metabolic Dysfunction Consistent with Premature Aging Results from Deletion of Pim Kinases

PubMed Central

Din, Shabana; Konstandin, Mathias H; Johnson, Bevan; Emathinger, Jacqueline; Völkers, Mirko; Toko, Haruhiro; Collins, Brett; Ormachea, Lucy; Samse, Kaitlen; Kubli, Dieter A; De La Torre, Andrea; Kraft, Andrew S; Gustafsson, Asa B; Kelly, Daniel P; Sussman, Mark A

2014-01-01

Rationale The senescent cardiac phenotype is accompanied by changes in mitochondrial function and biogenesis causing impairment in energy provision. The relationship between myocardial senescence and Pim kinases deserves attention since Pim-1 kinase is cardioprotective, in part, by preservation of mitochondrial integrity. Study of the pathological effects resulting from genetic deletion of all Pim kinase family members could provide important insight regarding cardiac mitochondrial biology and the aging phenotype. Objective Demonstrate myocardial senescence is promoted by loss of Pim leading to premature aging and aberrant mitochondrial function. Methods and Results Cardiac myocyte senescence was evident at three months of age in Pim Triple KnockOut (PTKO) mice, where all three isoforms of Pim kinase family members are genetically deleted. Cellular hypertrophic remodeling and fetal gene program activation was followed by heart failure at six months in PTKO mice. Metabolic dysfunction is an underlying cause of cardiac senescence and instigates a decline in cardiac function. Altered mitochondrial morphology is evident consequential to Pim deletion together with decreased ATP levels and increased phosphorylated AMPK, exposing an energy deficiency in PTKO mice. Expression of the genes encoding master regulators of mitochondrial biogenesis, PPARγ coactivator-1 (PGC-1) α and β were diminished in PTKO hearts, as were downstream targets included in mitochondrial energy transduction, including fatty acid oxidation. Reversal of the dysregulated metabolic phenotype was observed by overexpressing c-Myc, a downstream target of Pim kinases. Conclusion Pim kinases prevent premature cardiac aging and maintain a healthy pool of functional mitochondria leading to efficient cellular energetics. PMID:24916111

Transcription and translation are primary targets of Pim kinase inhibitor SGI-1776 in mantle cell lymphoma

PubMed Central

Yang, Qingshan; Chen, Lisa S.; Neelapu, Sattva S.; Miranda, Roberto N.; Medeiros, L. Jeffrey

2012-01-01

Proviral integration site for Moloney murine leukemia virus (Pim) kinases are serine/threonine/tyrosine kinases and oncoproteins that promote tumor progression. Three isoforms of Pim kinases have been identified and are known to phosphorylate numerous substrates, with regulatory functions in transcription, translation, cell cycle, and survival pathways. These kinases are involved in production, proliferation, and survival of normal B cells and are overexpressed in B-cell malignancies such as mantle cell lymphoma (MCL). SGI-1776 is a small mol-ecule and Pim kinase inhibitor with selectivity for Pim-1. We hypothesize that Pim kinase function can be inhibited by SGI-1776 in MCL and that inhibition of phosphorylation of downstream substrates will disrupt transcriptional, translational, and cell cycle processes and promote cell death. SGI-1776 treatment in 4 MCL cell lines resulted in apoptosis induction. Phosphorylation of transcription (c-Myc) and translation targets (4E-BP1), tested in Jeko-1 and Mino, was declined. Consistent with these data, Mcl-1 and cyclin D1 protein levels were decreased. Importantly, similar to cell line data, MCL primary cells but not normal cells showed similar inhibition of substrate phosphorylation and cytotoxicity from SGI-1776 treatment. Genetic knockdown of Pim-1/Pim-2 affected similar proteins in MCL cell lines. Collectively these data demonstrate Pim kinases as therapeutic targets in MCL. PMID:22955922

Transcription and translation are primary targets of Pim kinase inhibitor SGI-1776 in mantle cell lymphoma.

PubMed

Yang, Qingshan; Chen, Lisa S; Neelapu, Sattva S; Miranda, Roberto N; Medeiros, L Jeffrey; Gandhi, Varsha

2012-10-25

Proviral integration site for Moloney murine leukemia virus (Pim) kinases are serine/threonine/tyrosine kinases and oncoproteins that promote tumor progression. Three isoforms of Pim kinases have been identified and are known to phosphorylate numerous substrates, with regulatory functions in transcription, translation, cell cycle, and survival pathways. These kinases are involved in production, proliferation, and survival of normal B cells and are overexpressed in B-cell malignancies such as mantle cell lymphoma (MCL). SGI-1776 is a small molecule and Pim kinase inhibitor with selectivity for Pim-1. We hypothesize that Pim kinase function can be inhibited by SGI-1776 in MCL and that inhibition of phosphorylation of downstream substrates will disrupt transcriptional, translational, and cell cycle processes and promote cell death. SGI-1776 treatment in 4 MCL cell lines resulted in apoptosis induction. Phosphorylation of transcription (c-Myc) and translation targets (4E-BP1), tested in Jeko-1 and Mino, was declined. Consistent with these data, Mcl-1 and cyclin D1 protein levels were decreased. Importantly, similar to cell line data, MCL primary cells but not normal cells showed similar inhibition of substrate phosphorylation and cytotoxicity from SGI-1776 treatment. Genetic knockdown of Pim-1/Pim-2 affected similar proteins in MCL cell lines. Collectively these data demonstrate Pim kinases as therapeutic targets in MCL.

Removal of aniline from air and water by polymers of intrinsic microporosity (PIM-1) electrospun ultrafine fibers.

PubMed

Satilmis, Bekir; Uyar, Tamer

2018-04-15

This research aims to investigate the possibility of electrospun fibers from Polymers of Intrinsic Microporosity (PIM-1) as an alternative adsorbent for aniline removal from both air and aqueous solution. Adsorption properties of electrospun PIM-1 fibers were compared with powder and film form of PIM-1. While electrospun PIM-1 nanofibrous mat can adsorb 871 mg g -1 aniline from air, it can also adsorb 78 ± 5.4 mg g -1 aniline from aqueous environment when 50 mg L -1 aniline solution is used. The experimental maximum adsorption capacity of electrospun PIM-1 fibers was found as (q e ) 138 mg g -1 . Langmuir and Freundlich isotherm models have been studied and Langmuir model found more appropriate for aniline adsorption on electrospun PIM-1 fibers. The study reveals that self-standing electrospun fibrous mat of PIM-1 has shown potential to be used as an efficient adsorbent material for the adsorption of VOCs from air and aqueous system thanks to its fast kinetic and high adsorption capacity. Copyright © 2018 Elsevier Inc. All rights reserved.

Tricyclic Benzo[cd]azulenes Selectively Inhibit Activities of Pim Kinases and Restrict Growth of Epstein-Barr Virus-Transformed Cells

PubMed Central

Santio, Niina M.; Arnaudova, Ralica; Eerola, Sini K.; Rainio, Eeva-Marja; Aumüller, Ingo B.; Yli-Kauhaluoma, Jari; Koskinen, Päivi J.

2013-01-01

Oncogenic Pim family kinases are often overexpressed in human hematopoietic malignancies as well as in solid tumours. These kinases contribute to tumorigenesis by promoting cell survival and by enhancing resistance against chemotherapy and radiation therapy. Furthermore, we have recently shown that they increase the metastatic potential of adherent cancer cells. Here we describe identification of tricyclic benzo[cd]azulenes and their derivatives as effective and selective inhibitors of Pim kinases. These compounds inhibit Pim autophosphorylation and abrogate the anti-apoptotic effects of Pim kinases. They also reduce cancer cell motility and suppress proliferation of lymphoblastoid cell lines infected and immortalized by the Epstein-Barr virus. Thus, these novel Pim-selective inhibitors provide promising compounds for both research and therapeutic purposes. PMID:23405147

Rheological behavior of magnetic powder mixtures for magnetic PIM

NASA Astrophysics Data System (ADS)

Kim, Sung Hun; Kim, See Jo; Park, Seong Jin; Mun, Jun Ho; Kang, Tae Gon; Park, Jang Min

2012-06-01

Powder injection molding (PIM) is a promising manufacturing technology for the net-shape production of small, complex, and precise metal or ceramic components. In order to manufacture high quality magnets using PIM, the magneto-rheological (MR) properties of the PIM feedstock, i.e. magnetic powder-binder mixture, should be investigated experimentally and theoretically. The current research aims at comprehensive understanding of the rheological characteristics of the PIM feedstock. The feedstock used in the experiment consists of strontium ferrite powder and paraffin wax. Steady and oscillatory shear tests have been carried out using a plate-and-plate rheometer, under the influence of a uniform magnetic field applied externally. Rheological properties of the PIM feedstock have been measured and characterized for various conditions by changing the temperature, the powder fraction and the magnetic flux density.

The Pim kinase inhibitor SGI-1776 decreases cell surface expression of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and drug transport by Pim-1-dependent and -independent mechanisms

PubMed Central

Natarajan, Karthika; Bhullar, Jasjeet; Shukla, Suneet; Burcu, Mehmet; Chen, Zhe-Sheng; Ambudkar, Suresh V.; Baer, Maria R.

2013-01-01

Overexpression of the ATP-binding cassette (ABC) drug efflux proteins P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on malignant cells is associated with inferior chemotherapy outcomes. Both, ABCB1 and ABCG2, are substrates of the serine/threonine kinase Pim-1; Pim-1 knockdown decreases their cell surface expression, but SGI-1776, the first clinically tested Pim inhibitor, was shown to reverse drug resistance by directly inhibiting ABCB1-mediated transport. We sought to characterize Pim-1-dependent and -independent effects of SGI-1776 on drug resistance. SGI-1776 at the Pim-1-inhibitory and non-cytotoxic concentration of 1 μM decreased the IC50s of the ABCG2 and ABCB1 substrate drugs in cytotoxicity assays in resistant cells, with no effect on the IC50 of non-substrate drug, nor in parental cells. SGI-1776 also increased apoptosis of cells overexpressing ABCG2 or ABCB1 exposed to substrate chemotherapy drugs and decreased their colony formation in the presence of substrate, but not non-substrate, drugs, with no effect on parental cells. SGI-1776 decreased ABCB1 and ABCG2 surface expression on K562/ABCB1 and K562/ABCG2 cells, respectively, with Pim-1 overexpression, but not HL60/VCR and 8226/MR20 cells, with lower-level Pim-1 expression. Finally, SGI-1776 inhibited uptake of ABCG2 and ABCB1 substrates in a concentration-dependent manner irrespective of Pim-1 expression, inhibited ABCB1 and ABCG2 photoaffinity labeling with the transport substrate [125I]iodoarylazidoprazosin ([125I]IAAP) and stimulated ABCB1 and ABCG2 ATPase activity. Thus SGI-1776 decreases cell surface expression of ABCB1 and ABCG2 and inhibits drug transport by Pim-1-dependent and -independent mechanisms, respectively. Decrease in ABCB1 and ABCG2 cell surface expression mediated by Pim-1 inhibition represents a novel mechanism of chemosensitization. PMID:23261525

The Pim kinase inhibitor SGI-1776 decreases cell surface expression of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and drug transport by Pim-1-dependent and -independent mechanisms.

PubMed

Natarajan, Karthika; Bhullar, Jasjeet; Shukla, Suneet; Burcu, Mehmet; Chen, Zhe-Sheng; Ambudkar, Suresh V; Baer, Maria R

2013-02-15

Overexpression of the ATP-binding cassette (ABC) drug efflux proteins P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on malignant cells is associated with inferior chemotherapy outcomes. Both, ABCB1 and ABCG2, are substrates of the serine/threonine kinase Pim-1; Pim-1 knockdown decreases their cell surface expression, but SGI-1776, the first clinically tested Pim inhibitor, was shown to reverse drug resistance by directly inhibiting ABCB1-mediated transport. We sought to characterize Pim-1-dependent and -independent effects of SGI-1776 on drug resistance. SGI-1776 at the Pim-1-inhibitory and non-cytotoxic concentration of 1 μM decreased the IC(50)s of the ABCG2 and ABCB1 substrate drugs in cytotoxicity assays in resistant cells, with no effect on the IC(50) of non-substrate drug, nor in parental cells. SGI-1776 also increased apoptosis of cells overexpressing ABCG2 or ABCB1 exposed to substrate chemotherapy drugs and decreased their colony formation in the presence of substrate, but not non-substrate, drugs, with no effect on parental cells. SGI-1776 decreased ABCB1 and ABCG2 surface expression on K562/ABCB1 and K562/ABCG2 cells, respectively, with Pim-1 overexpression, but not HL60/VCR and 8226/MR20 cells, with lower-level Pim-1 expression. Finally, SGI-1776 inhibited uptake of ABCG2 and ABCB1 substrates in a concentration-dependent manner irrespective of Pim-1 expression, inhibited ABCB1 and ABCG2 photoaffinity labeling with the transport substrate [(125)I]iodoarylazidoprazosin ([(125)I]IAAP) and stimulated ABCB1 and ABCG2 ATPase activity. Thus SGI-1776 decreases cell surface expression of ABCB1 and ABCG2 and inhibits drug transport by Pim-1-dependent and -independent mechanisms, respectively. Decrease in ABCB1 and ABCG2 cell surface expression mediated by Pim-1 inhibition represents a novel mechanism of chemosensitization. Copyright © 2012 Elsevier Inc. All rights reserved.

[Effects of Pim-1 inhibitor on mouse model of inflammatory bowel disease induced by TNBS].

PubMed

Ou, Rong; Shen, Yueming; Zeng, Ya; Zou, Lingzhi; Jiang, Na; Xu, Meihua

2018-05-28

To explore the role of Pim-1 in the pathology of inflammatory bowel disease and the potential effect of Pim-1 inhibitor on treating such disease.
 Methods: Forty-five BALB/c mice were randomly divided into 5 groups (n=9): A normal control group, a inflammatory bowel disease group, two different dose of Pim-1 inhibitor treatment groups, and steroidhormone treatment group. The model of inflammatory bowel disease was induced by intracolonic administration of 2, 4, 6-trinitrobenzenestdfonic acid (TNBS) and ethanol mixture. Mice were treated with Pim-1 inhibitor [intraperitoneal inject, 5 or 10 mg/(kg.d)] for 5 days and prednisone (intragastric administration, 0.1 mg/d) for 5 days. The DAI, colon length, gross score and pathological grade were evaluated. The expressions of T cell master transcription factors T-box expressed in T cells (T-bet), GATA binding protein 3 (GATA-3), RA orphan receptorγ (RORγt) and forkhead box P3 (Foxp3) were measured by Real-time PCR and Western blot, respectively.
 Results: Pim-1 inhibitor and prednisone showed therapeutic effect on acute TNBS colitis in vivo. GATA3 and RORγt were significantly up-regulated in acute TNBS colitis (P<0.05). In contrast, the expression of Foxp3 was suppressed in the inflammatory bowel disease group, whereas it did not cause any significant change in T-bet expression (P>0.05). Administration of Pim-1 inhibitor and prednisone resulted in suppression of GATA3, RORγt expression, and the increase of Foxp3 expression (P<0.05). Administration of Pim-1 inhibitor and prednisone resulted in inhibition of T-bet mRNA expression (P<0.05), but only prednisone could inhibit T-bet protein expression (P>0.05).
 Conclusion: Pim-1 inhibitor significantly suppresses Th2- and Th17-type immune responses. Furthermore, Pim-1 inhibitor could induce T-cell differentiation towards a Treg phenotype. Pim-1 inhibitor has therapeutic effect on acute TNBS colitis.

Potentially inappropriate drug prescription in the elderly in France: a population-based study from the French National Insurance Healthcare system.

PubMed

Bongue, B; Laroche, M L; Gutton, S; Colvez, A; Guéguen, R; Moulin, J J; Merle, L

2011-12-01

Inappropriate prescribing is a known risk factor for adverse drug event occurrence in the elderly. In various countries, several studies have used insurance healthcare databases to estimate the national prevalence of potentially inappropriate medications (PIM) in the elderly, as defined by explicit PIM lists. Recently, a representative sample of the French National Insurance Healthcare database, known as the "Echantillon Généraliste des Bénéficiaires" (EGB), was created, making it possible to assess the quality of drug prescription in France. Our objective was to evaluate the prevalence and the regional distribution of PIM prescription in the elderly aged 75 years and over in France, using the French PIM list and the EGB database. The list of drugs reimbursed to patients aged 75 years and over from 1 March 2007 to 29 February 2008 was extracted from the EGB. Drugs were classified as inappropriate using the French PIM list. A PIM user was defined as a person receiving at least one PIM reimbursement during the study period. Interregion variability was estimated from logistic regression. In 53.6% (95% CI: 53.0-54.1) of the elderly aged 75 years and over, at least one PIM was given during the study period. The three main drug groups identified were cerebral vasodilators (19.4%), drugs with antimuscarinic properties (19.3%), and long half-life benzodiazepines (17.8%). There was an important disparity in PIM prescription among the French regions. In 14 out of 22 regions, the risk of PIM prescription was significantly elevated. This geographical variation differed for the different drug groups. PIM prescription in the elderly is a major and worrying problem in France. As in other countries, recent accessibility of the National Insurance Healthcare database makes it possible to create local indicators that the regional health agencies could use to manage public health policy in closer alignment to the needs of the patients within each French region.

Pim1 kinase is upregulated in glioblastoma multiforme and mediates tumor cell survival

PubMed Central

Herzog, Susann; Fink, Matthias Alexander; Weitmann, Kerstin; Friedel, Claudius; Hadlich, Stefan; Langner, Sönke; Kindermann, Katharina; Holm, Tobias; Böhm, Andreas; Eskilsson, Eskil; Miletic, Hrvoje; Hildner, Markus; Fritsch, Michael; Vogelgesang, Silke; Havemann, Christoph; Ritter, Christoph Alexander; Meyer zu Schwabedissen, Henriette Elisabeth; Rauch, Bernhard; Hoffmann, Wolfgang; Kroemer, Heyo Klaus; Schroeder, Henry; Bien-Möller, Sandra

2015-01-01

Background The current therapy for glioblastoma multiforme (GBM), the most aggressive and common primary brain tumor of adults, involves surgery and a combined radiochemotherapy that controls tumor progression only for a limited time window. Therefore, the identification of new molecular targets is highly necessary. Inhibition of kinases has become a standard of clinical oncology, and thus the oncogenic kinase Pim1 might represent a promising target for improvement of GBM therapy. Methods Expression of Pim1 and associated signaling molecules was analyzed in human GBM samples, and the potential role of this kinase in patients' prognosis was evaluated. Furthermore, we analyzed the in vivo role of Pim1 in GBM cell growth in an orthotopic mouse model and examined the consequences of Pim1 inhibition in vitro to clarify underlying pathways. Results In comparison with normal brain, a strong upregulation of Pim1 was demonstrated in human GBM samples. Notably, patients with short overall survival showed a significantly higher Pim1 expression compared with GBM patients who lived longer than the median. In vitro experiments with GBM cells and analysis of patients' GBM samples suggest that Pim1 regulation is dependent on epidermal growth factor receptor. Furthermore, inhibition of Pim1 resulted in reduced cell viability accompanied by decreased cell numbers and increased apoptotic cells, as seen by elevated subG1 cell contents and caspase-3 and -9 activation, as well as modulation of several cell cycle or apoptosis regulatory proteins. Conclusions Altogether, Pim1 could be a novel therapeutic target, which should be further analyzed to improve the outcome of patients with aggressive GBM. PMID:25155357

Potentially Inappropriate Prescribing in Disabled Older Patients with Chronic Diseases: A Screening Tool of Older Persons' Potentially Inappropriate Prescriptions versus Beers 2012 Criteria.

PubMed

Yang, Po-Jen; Lee, Yuan-Ti; Tzeng, Shu-Ling; Lee, Huei-Chao; Tsai, Chin-Feng; Chen, Chun-Chieh; Chen, Shiuan-Chih; Lee, Meng-Chih

2015-01-01

To evaluate the prescription of potentially inappropriate medications (PIM), using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) and Beers criteria, to disabled older people. One hundred and forty-one patients aged ≥65 years with Barthel scale scores ≤60 and a regular intake of medication for chronic diseases at Chung Shan Medical University Hospital from July to December 2012 were included, and their medical records were reviewed. Comprehensive patient information was extracted from the patients' medical notes. The STOPP and Beers 2012 criteria were used separately to identify PIM, and logistic regression analyses were performed to identify risk factors for PIM. The optimal cutoff for the number of medications prescribed for predicting PIM was estimated using the Youden index. Of the 141 patients, 94 (66.7%) and 94 (66.7%) had at least one PIM identified by the STOPP and Beers criteria, respectively. In multivariate analysis, PIM identified by the Beers criteria were associated with the prescription of multiple medications (p = 0.013) and the presence of psychiatric diseases (p < 0.001), whereas PIM identified by the STOPP criteria were only associated with the prescription of multiple medications (p = 0.008). The optimal cutoff for the number of medications prescribed for predicting PIM by using the STOPP or Beers criteria was 6. After adjustment for covariates, patients prescribed ≥6 medications had a significantly higher risk of PIM, identified using the STOPP or Beers criteria, compared to patients prescribed <6 medications (both p < 0.05). This study revealed a high frequency of PIM in disabled older patients with chronic diseases, particularly those prescribed ≥6 medications. © 2015 S. Karger AG, Basel.

Potentially Inappropriate Prescribing in Disabled Older Patients with Chronic Diseases: A Screening Tool of Older Persons' Potentially Inappropriate Prescriptions versus Beers 2012 Criteria

PubMed Central

Yang, Po-Jen; Lee, Yuan-Ti; Tzeng, Shu-Ling; Lee, Huei-Chao; Tsai, Chin-Feng; Chen, Chun-Chieh; Chen, Shiuan-Chih; Lee, Meng-Chih

2015-01-01

Objective To evaluate the prescription of potentially inappropriate medications (PIM), using the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) and Beers criteria, to disabled older people. Subjects and Methods One hundred and forty-one patients aged ≥65 years with Barthel scale scores ≤60 and a regular intake of medication for chronic diseases at Chung Shan Medical University Hospital from July to December 2012 were included, and their medical records were reviewed. Comprehensive patient information was extracted from the patients' medical notes. The STOPP and Beers 2012 criteria were used separately to identify PIM, and logistic regression analyses were performed to identify risk factors for PIM. The optimal cutoff for the number of medications prescribed for predicting PIM was estimated using the Youden index. Results Of the 141 patients, 94 (66.7%) and 94 (66.7%) had at least one PIM identified by the STOPP and Beers criteria, respectively. In multivariate analysis, PIM identified by the Beers criteria were associated with the prescription of multiple medications (p = 0.013) and the presence of psychiatric diseases (p < 0.001), whereas PIM identified by the STOPP criteria were only associated with the prescription of multiple medications (p = 0.008). The optimal cutoff for the number of medications prescribed for predicting PIM by using the STOPP or Beers criteria was 6. After adjustment for covariates, patients prescribed ≥6 medications had a significantly higher risk of PIM, identified using the STOPP or Beers criteria, compared to patients prescribed <6 medications (both p < 0.05). Conclusion This study revealed a high frequency of PIM in disabled older patients with chronic diseases, particularly those prescribed ≥6 medications. PMID:26279164

Spi1 GTPase interacts with RCC1 to maintain interdependency of cell cycle events.

PubMed

Matsumoto, T; Beach, D

1991-01-01

A mutant which can enter mitosis at any cell cycle stage has been isolated and characterized in fission yeast. The pim1 (premature initiation of mitosis) mutant prearrested at G1/S can develop a mitotic spindle and has tightly condensed chromosomes upon shift to the restrictive temperature. pim1-induced mitosis requires maturation promoting factor (MPF) activity, but not the essential mitotic inducer, cdc25. The pim1+ gene encodes a homolog of regulator of chromosome condensation 1 (RCC1), a regulator of onset of mitosis in mammalian cells. A multicopy suppressor of pim1, spi1, was isolated, and found to encode a 25 kDa GTPase. The primary sequence of the spi1 GTPase shows extensive identity (80%) to human TC4, whose function is unknown. The spi1/TC4 GTPase defines a novel class in the "ras-like" GTPase family, which is distinct from ras, rho, or ypt. Disruption of the spi1+ gene causes genomic instability in a heterozygous diploid. These genetic data suggest that pim1+ and spi1+ interact to coordinate correct entry into mitosis. Immunological experiments demonstrate that the pim1+ and spi1+ products are physically associated. Mutation in the pim1 gene results in lowered affinity of the protein for the spi1 protein in vitro, which may explain why high dosages of the spi1 protein can rescue the pim1 mutant in vivo. The pim1/spi1 complex dissociates in the presence of Mg2+ and GTP. The current data suggests that pim1+ acts as a GTP exchanger for the spi1 GTPase.

The products of the thermal decomposition of CH{sub 3}CHO

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

Vasiliou, AnGayle; National Renewable Energy Laboratory, 1617 Cole Blvd., Golden, Colorado 80401; Piech, Krzysztof M.

2011-07-07

We have used a heated 2 cm x 1 mm SiC microtubular ({mu}tubular) reactor to decompose acetaldehyde: CH{sub 3}CHO +{Delta}{yields} products. Thermal decomposition is followed at pressures of 75-150 Torr and at temperatures up to 1675 K, conditions that correspond to residence times of roughly 50-100 {mu}s in the {mu}tubular reactor. The acetaldehyde decomposition products are identified by two independent techniques: vacuum ultraviolet photoionization mass spectroscopy (PIMS) and infrared (IR) absorption spectroscopy after isolation in a cryogenic matrix. Besides CH{sub 3}CHO, we have studied three isotopologues, CH{sub 3}CDO, CD{sub 3}CHO, and CD{sub 3}CDO. We have identified the thermal decomposition productsmore » CH{sub 3} (PIMS), CO (IR, PIMS), H (PIMS), H{sub 2} (PIMS), CH{sub 2}CO (IR, PIMS), CH{sub 2}=CHOH (IR, PIMS), H{sub 2}O (IR, PIMS), and HC{identical_to}CH (IR, PIMS). Plausible evidence has been found to support the idea that there are at least three different thermal decomposition pathways for CH{sub 3}CHO; namely, radical decomposition: CH{sub 3}CHO +{Delta}{yields} CH{sub 3}+[HCO]{yields} CH{sub 3}+ H + CO; elimination: CH{sub 3}CHO +{Delta}{yields} H{sub 2}+ CH{sub 2}=C=O; isomerization/elimination: CH{sub 3}CHO +{Delta}{yields}[CH{sub 2}=CH-OH]{yields} HC{identical_to}CH + H{sub 2}O. An interesting result is that both PIMS and IR spectroscopy show compelling evidence for the participation of vinylidene, CH{sub 2}=C:, as an intermediate in the decomposition of vinyl alcohol: CH{sub 2}=CH-OH +{Delta}{yields}[CH{sub 2}=C:]+ H{sub 2}O {yields} HC{identical_to}CH + H{sub 2}O.« less

Characterization of the gene encoding the polymorphic immunodominant molecule, a neutralizing antigen of Theileria parva

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

Toye, P.G.; Metzelaar, M.J.; Wijngaard, P.L.J.

1995-08-01

Theileria parva, a tick-transmitted protozoan parasite related to Plasmodium spp., causes the disease East Coast fever, an acute and usually fatal lymphoproliferative disorder of cattle in Africa. Previous studies using sera from cattle that have survived infection identified a polymorphic immunodominant molecule (PIM) that is expressed by both the infective sporozoite stage of the parasite and the intracellular schizont. Here we show that mAb specific for the PIM Ag can inhibit sporozoite invasion of lymphocytes in vitro. A cDNA clone encoding the PIM Ag of the T. parva (Muguga) stock was obtained by using these mAb in a novel eukaryoticmore » expression cloning system that allows isolation of cDNA encoding cytoplasmic or surface Ags. To establish the molecular basis of the polymorphism of PIM, the cDNA of the PIM Ag from a buffalo-derived T. parva stock was isolated and its sequence was compared with that of the cattle-derived Muguga PIM. The two cDNAs showed considerable identity in both the 5{prime} and 3{prime} regions, but there was substantial sequence divergence in the central regions. Several types of repeated sequences were identified in the variant regions. In the Muguga form of the molecule, there were five tandem repeats of the tetrapeptide, QPEP, that were shown, by transfection of a deleted version of the PIM gene, not to react with several anti-PIM mAbs. By isolating and sequencing the genomic version of the gene, we identified two small introns in the 3{prime} region of the gene. Finally, we showed that polyclonal rat Abs against recombinant PIM neutralize sporozoite infectivity in vitro, suggesting that the PIM Ag should be evaluated for its capacity to immunize cattle against East Coast Fever.« less

Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells.

PubMed

Chen, Lisa S; Redkar, Sanjeev; Bearss, David; Wierda, William G; Gandhi, Varsha

2009-11-05

Pim kinases are involved in B-cell development and are overexpressed in B-cell chronic lymphocytic leukemia (CLL). We hypothesized that Pim kinase inhibition would affect B-cell survival. Identified from a screen of imidazo[1,2-b]pyridazine compounds, SGI-1776 inhibits Pim-1, Pim-2, and Pim-3. Treatment of CLL cells with SGI-1776 results in a concentration-dependent induction of apoptosis. To elucidate its mechanism of action, we evaluated the effect of SGI-1776 on Pim kinase function. Unlike in replicating cells, phosphorylation of traditional Pim-1 kinase targets, phospho-Bad (Ser112) and histone H3 (Ser10), and cell-cycle proteins were unaffected by SGI-1776, suggesting an alternative mechanism in CLL. Protein levels of total c-Myc as well as phospho-c-Myc(Ser62), a Pim-1 target site, were decreased after SGI-1776 treatment. Levels of antiapoptotic proteins Bcl-2, Bcl-X(L), XIAP, and proapoptotic Bak and Bax were unchanged; however, a significant reduction in Mcl-1 was observed that was not caused by caspase-mediated cleavage of Mcl-1 protein. The mechanism of decline in Mcl-1 was at the RNA level and was correlated with inhibition of global RNA synthesis. Consistent with a decline in new RNA synthesis, MCL-1 transcript levels were decreased after treatment with SGI-1776. These data suggest that SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction.

Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells

PubMed Central

Chen, Lisa S.; Redkar, Sanjeev; Bearss, David; Wierda, William G.

2009-01-01

Pim kinases are involved in B-cell development and are overexpressed in B-cell chronic lymphocytic leukemia (CLL). We hypothesized that Pim kinase inhibition would affect B-cell survival. Identified from a screen of imidazo[1,2-b]pyridazine compounds, SGI-1776 inhibits Pim-1, Pim-2, and Pim-3. Treatment of CLL cells with SGI-1776 results in a concentration-dependent induction of apoptosis. To elucidate its mechanism of action, we evaluated the effect of SGI-1776 on Pim kinase function. Unlike in replicating cells, phosphorylation of traditional Pim-1 kinase targets, phospho-Bad (Ser112) and histone H3 (Ser10), and cell-cycle proteins were unaffected by SGI-1776, suggesting an alternative mechanism in CLL. Protein levels of total c-Myc as well as phospho-c-Myc(Ser62), a Pim-1 target site, were decreased after SGI-1776 treatment. Levels of antiapoptotic proteins Bcl-2, Bcl-XL, XIAP, and proapoptotic Bak and Bax were unchanged; however, a significant reduction in Mcl-1 was observed that was not caused by caspase-mediated cleavage of Mcl-1 protein. The mechanism of decline in Mcl-1 was at the RNA level and was correlated with inhibition of global RNA synthesis. Consistent with a decline in new RNA synthesis, MCL-1 transcript levels were decreased after treatment with SGI-1776. These data suggest that SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction. PMID:19734450

Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia.

PubMed

Chen, Lisa S; Redkar, Sanjeev; Taverna, Pietro; Cortes, Jorge E; Gandhi, Varsha

2011-07-21

Pim kinases are Ser/Thr kinases with multiple substrates that affect survival pathways. These proteins are overexpressed in acute myeloid leukemia (AML) blasts and we hypothesized that Pim kinase inhibition would affect AML cell survival. Imidazo[1,2-b]pyridazine compound, SGI-1776 inhibits Pim-1, Pim-2 and Pim-3, and was evaluated in AML-cell line, -xenograft model, and -primary blasts. Treatment of AML cells with SGI-1776 results in a concentration-dependent induction of apoptosis and we investigated its effect on Pim kinase functions. Phosphorylation of traditional Pim kinase targets, c-Myc(Ser62) and 4E-BP1 (Thr36/Thr47), were both decreased in actively cycling AML cell lines MV-4-11, MOLM-13 and OCI-AML-3. Levels of antiapoptotic proteins Bcl-2, Bcl-x(L), XIAP, and proapoptotic Bak and Bax were unchanged; however, a significant reduction in Mcl-1 was observed. This was correlated with inhibition of global RNA and protein synthesis and MCL-1 transcript decline after SGI-1776 treatment. These data suggest that SGI-1776 mechanism in AML involves Mcl-1 protein reduction. Consistent with cell line data, xenograft model studies with mice bearing MV-4-11 tumors showed efficacy with SGI-1776. Importantly, SGI-1776 was also cytotoxic in AML primary cells, irrespective of FLT3 mutation status and resulted in Mcl-1 protein decline. Pim kinase inhibition may be a new strategy for AML treatment.

Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia

PubMed Central

Chen, Lisa S.; Redkar, Sanjeev; Taverna, Pietro; Cortes, Jorge E.

2011-01-01

Pim kinases are Ser/Thr kinases with multiple substrates that affect survival pathways. These proteins are overexpressed in acute myeloid leukemia (AML) blasts and we hypothesized that Pim kinase inhibition would affect AML cell survival. Imidazo[1,2-b]pyridazine compound, SGI-1776 inhibits Pim-1, Pim-2 and Pim-3, and was evaluated in AML-cell line, -xenograft model, and -primary blasts. Treatment of AML cells with SGI-1776 results in a concentration-dependent induction of apoptosis and we investigated its effect on Pim kinase functions. Phosphorylation of traditional Pim kinase targets, c-Myc(Ser62) and 4E-BP1 (Thr36/Thr47), were both decreased in actively cycling AML cell lines MV-4-11, MOLM-13 and OCI-AML-3. Levels of antiapoptotic proteins Bcl-2, Bcl-xL, XIAP, and proapoptotic Bak and Bax were unchanged; however, a significant reduction in Mcl-1 was observed. This was correlated with inhibition of global RNA and protein synthesis and MCL-1 transcript decline after SGI-1776 treatment. These data suggest that SGI-1776 mechanism in AML involves Mcl-1 protein reduction. Consistent with cell line data, xenograft model studies with mice bearing MV-4-11 tumors showed efficacy with SGI-1776. Importantly, SGI-1776 was also cytotoxic in AML primary cells, irrespective of FLT3 mutation status and resulted in Mcl-1 protein decline. Pim kinase inhibition may be a new strategy for AML treatment. PMID:21628411

Mixed Matrix Membranes of Boron Icosahedron and Polymers of Intrinsic Microporosity (PIM-1) for Gas Separation

PubMed Central

Khan, Muntazim Munir; Shishatskiy, Sergey; Filiz, Volkan

2018-01-01

This work reports on the preparation and gas transport performance of mixed matrix membranes (MMMs) based on the polymer of intrinsic microporosity (PIM-1) and potassium dodecahydrododecaborate (K2B12H12) as inorganic particles (IPs). The effect of IP loading on the gas separation performance of these MMMs was investigated by varying the IP content (2.5, 5, 10 and 20 wt %) in a PIM-1 polymer matrix. The derived MMMs were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), single gas permeation tests and sorption measurement. The PIM1/K2B12H12 MMMs show good dispersion of the IPs (from 2.5 to 10 wt %) in the polymer matrix. The gas permeability of PIM1/K2B12H12 MMMs increases as the loading of IPs increases (up to 10 wt %) without sacrificing permselectivity. The sorption isotherm in PIM-1 and PIM1/K2B12H12 MMMs demonstrate typical dual-mode sorption behaviors for the gases CO2 and CH4. PMID:29301312

Case Study: Using The OMG SWRADIO Profile and SDR Forum Input for NASA's Space Telecommunications Radio System

NASA Technical Reports Server (NTRS)

Briones, Janette C.; Handler, Louis M.; Hall, Steve C.; Reinhart, Richard C.; Kacpura, Thomas J.

2009-01-01

The Space Telecommunication Radio System (STRS) standard is a Software Defined Radio (SDR) architecture standard developed by NASA. The goal of STRS is to reduce NASA s dependence on custom, proprietary architectures with unique and varying interfaces and hardware and support reuse of waveforms across platforms. The STRS project worked with members of the Object Management Group (OMG), Software Defined Radio Forum, and industry partners to leverage existing standards and knowledge. This collaboration included investigating the use of the OMG s Platform-Independent Model (PIM) SWRadio as the basis for an STRS PIM. This paper details the influence of the OMG technologies on the STRS update effort, findings in the STRS/SWRadio mapping, and provides a summary of the SDR Forum recommendations.

Universal Payload Information Management

NASA Technical Reports Server (NTRS)

Elmore, Ralph B.

2003-01-01

As the overall manager and integrator of International Space Station (ISS) science payloads, the Payload Operations Integration Center (POIC) at Marshall Space Flight Center has a critical need to provide an information management system for exchange and control of ISS payload files as well as to coordinate ISS payload related operational changes. The POIC's information management system has a fundamental requirement to provide secure operational access not only to users physically located at the POIC, but also to remote experimenters and International Partners physically located in different parts of the world. The Payload Information Management System (PIMS) is a ground-based electronic document configuration management and collaborative workflow system that was built to service the POIC's information management needs. This paper discusses the application components that comprise the PIMS system, the challenges that influenced its design and architecture, and the selected technologies it employs. This paper will also touch on the advantages of the architecture, details of the user interface, and lessons learned along the way to a successful deployment. With PIMS, a sophisticated software solution has been built that is not only universally accessible for POIC customer s information management needs, but also universally adaptable in implementation and application as a generalized information management system.

Perception of Not Having Enough Milk and Actual Milk Production of First-Time Breastfeeding Mothers: Is There a Difference?

PubMed

Galipeau, Roseline; Dumas, Louise; Lepage, Mario

2017-05-01

This study aimed to determine the relationship between perceived insufficient milk supply (PIMS) and actual insufficient milk supply (AIMS) and the relative contributions of physiological and psychosocial variables on both PIMS and AIMS of first-time breastfeeding mothers. Data were collected among 123 breastfeeding mothers at a Canadian, French-speaking maternal care hospital. Birth events, breastfeeding practices, infant and maternal capacities, and PIMS and AIMS were collected at 48 hours after birth, postnatal weeks 2 and 6. No significant relationship was found between PIMS and AIMS. Maternal breastfeeding self-efficacy and number of feeds were related to PIMS at week 2, and skin-to-skin contact at birth and number of feeds were related to AIMS as measured by 24-hour milk production at week 2. Maternal breastfeeding self-efficacy impacts PIMS. Interventions should be directed to increase maternal confidence in breastfeeding, which in turn influences breastfeeding duration.

Comparison of peri-implant bone formation around injection-molded and machined surface zirconia implants in rabbit tibiae

PubMed Central

Kim, Hong-Kyun; Woo, Kyung mi; Shon, Won-Jun; Ahn, Jin-Soo; Cha, Seunghee; Park, Young-Seok

2017-01-01

The aim of this study was to compare osseointegration and surface characteristics of zirconia implants made by the powder injection molding (PIM) technique and made by the conventional milling procedure in rabbit tibiae. Surface characteristics of 2 types of implant were evaluated. Sixteeen rabbits received 2 types of external hex implants with similar geometry, machined zirconia implants and PIM zirconia implants, in the tibiae. Removal torque tests and histomorphometric analyses were performed. The roughness of PIM zirconia implants was higher than that of machined zirconia implants. The PIM zirconia implants exhibited significantly higher bone-implant contact and removal torque values than the machined zirconia implants (P < 0.001). The osseointegration of the PIM zirconia implant is promising, and PIM, using the roughened mold etching technique, can produce substantially rough surfaces on zirconia implants. PMID:26235717

A qualitative study on personal information management (PIM) in clinical and basic sciences faculty members of a medical university in Iran

PubMed Central

Sedghi, Shahram; Abdolahi, Nida; Azimi, Ali; Tahamtan, Iman; Abdollahi, Leila

2015-01-01

Background: Personal Information Management (PIM) refers to the tools and activities to save and retrieve personal information for future uses. This study examined the PIM activities of faculty members of Iran University of Medical Sciences (IUMS) regarding their preferred PIM tools and four aspects of acquiring, organizing, storing and retrieving personal information. Methods: The qualitative design was based on phenomenology approach and we carried out 37 interviews with clinical and basic sciences faculty members of IUMS in 2014. The participants were selected using a random sampling method. All interviews were recorded by a digital voice recorder, and then transcribed, codified and finally analyzed using NVivo 8 software. Results: The use of PIM electronic tools (e-tools) was below expectation among the studied sample and just 37% had reasonable knowledge of PIM e-tools such as, external hard drivers, flash memories etc. However, all participants used both paper and electronic devices to store and access information. Internal mass memories (in Laptops) and flash memories were the most used e-tools to save information. Most participants used "subject" (41.00%) and "file name" (33.7 %) to save, organize and retrieve their stored information. Most users preferred paper-based rather than electronic tools to keep their personal information. Conclusion: Faculty members had little knowledge about PIM techniques and tools. Those who organized personal information could easier retrieve the stored information for future uses. Enhancing familiarity with PIM tools and training courses of PIM tools and techniques are suggested. PMID:26793648

The EU(7)-PIM list: a list of potentially inappropriate medications for older people consented by experts from seven European countries.

PubMed

Renom-Guiteras, Anna; Meyer, Gabriele; Thürmann, Petra A

2015-07-01

The aim of the study was to develop a European list of potentially inappropriate medications (PIM) for older people, which can be used for the analysis and comparison of prescribing patterns across European countries and for clinical practice. A preliminary PIM list was developed, based on the German PRISCUS list of potentially inappropriate medications and other PIM lists from the USA, Canada and France. Thirty experts on geriatric prescribing from Estonia, Finland, France, the Netherlands, Spain and Sweden participated; eight experts performed a structured expansion of the list, suggesting further medications; twenty-seven experts participated in a two-round Delphi survey assessing the appropriateness of drugs and suggesting dose adjustments and therapeutic alternatives. Finally, twelve experts completed a brief final survey to decide upon issues requiring further consensus. Experts reached a consensus that 282 chemical substances or drug classes from 34 therapeutic groups are PIM for older people; some PIM are restricted to a certain dose or duration of use. The PIM list contains suggestions for dose adjustments and therapeutic alternatives. The European Union (EU)(7)-PIM list is a screening tool, developed with participation of experts from seven European countries, that allows identification and comparison of PIM prescribing patterns for older people across European countries. It can also be used as a guide in clinical practice, although it does not substitute the decision-making process of individualised prescribing for older people. Further research is needed to investigate the feasibility and applicability and, finally, the clinical benefits of the newly developed list.

Potentially inappropriate medication prescribing is associated with socioeconomic factors: a spatial analysis in the French Nord-Pas-de-Calais Region.

PubMed

Beuscart, Jean-Baptiste; Genin, Michael; Dupont, Corrine; Verloop, David; Duhamel, Alain; Defebvre, Marguerite-Marie; Puisieux, François

2017-07-01

potentially inappropriate medication (PIM) prescribing is common in older people and leads to adverse events and hospital admissions. to determine whether prevalence of PIM prescribing varies according to healthcare supply and socioeconomic status. all prescriptions dispensed at community pharmacies for patients aged 75 and older between 1 January  and 31 March 2012 were retrieved from French Health Insurance Information System of the Nord-Pas-de-Calais Region for patients affiliated to the Social Security scheme. PIM was defined according to the French list of Laroche. The geographic distribution of PIM prescribing in this area was analysed using spatial scan statistics. overall, 65.6% (n = 207,979) of people aged 75 years and over living in the Nord-Pas-de-Calais Region were included. Among them, 32.6% (n = 67,863) received at least one PIM. The spatial analysis identified 16 and 10 clusters of municipalities with a high and a low prevalence of PIM prescribing, respectively. Municipalities with a low prevalence of PIM were characterised by a high socioeconomic status whereas those with a high prevalence of PIM were mainly characterised by a low socioeconomic status, such as a high unemployment rate and low household incomes. Markers of healthcare supply were weakly associated with high or low prevalence clusters. significant geographic variation in PIM prescribing was observed in the study territory and was mainly associated with socioeconomic factors. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

Factors associated with the use of potentially inappropriate medications by older adults with cancer.

PubMed

Reis, Cristiane Moreira; Dos Santos, Andrezza Gouvêa; de Jesus Souza, Paula; Reis, Adriano Max Moreira

2017-07-01

To determine the frequency and the factors associated with the use of potentially inappropriate medications (PIMs) by older adults with cancer at an onco-haematology ambulatory clinic of a teaching hospital in Brazil. Patients aged 60years or older (n=160) subjected to parenteral antineoplastic chemotherapy from May to December 2015 and treated with one or more medications in the ambulatory clinic were interviewed. Data on medications, comorbidities, oncological diagnosis, and functional status were recorded. Functionality was determined using the Vulnerable Elders Survey (VES-13). PIMs were determined using the 2015 Beers Criteria. Logistic regression was used to determine the factors associated with the use of PIMs. A total of 78 (48.1%) older adults used at least one PIM. The PIMs to be avoided by older adults were proton pump inhibitors (33.3%), antiemetics (10.5%), long-acting benzodiazepines (10.5%), and antidepressants (7.6%). Multivariate analysis indicated that PIMs were associated with the use of five or more medications (odds ratio, 3.14; 95% confidence interval, 1.4-6.6), after adjusting for the number of medications, number of comorbidities, depression, and arthritis/arthrosis. The frequency of use of PIMs by older adults at the investigated ambulatory clinic was high. Polypharmacy was positively associated with the use of PIMs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pim1 inhibition as a novel therapeutic strategy for Alzheimer's disease.

PubMed

Velazquez, Ramon; Shaw, Darren M; Caccamo, Antonella; Oddo, Salvatore

2016-07-13

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. Clinically, AD is characterized by impairments of memory and cognitive functions. Accumulation of amyloid-β (Aβ) and neurofibrillary tangles are the prominent neuropathologies in patients with AD. Strong evidence indicates that an imbalance between production and degradation of key proteins contributes to the pathogenesis of AD. The mammalian target of rapamycin (mTOR) plays a key role in maintaining protein homeostasis as it regulates both protein synthesis and degradation. A key regulator of mTOR activity is the proline-rich AKT substrate 40 kDa (PRAS40), which directly binds to mTOR and reduces its activity. Notably, AD patients have elevated levels of phosphorylated PRAS40, which correlate with Aβ and tau pathologies as well as cognitive deficits. Physiologically, PRAS40 phosphorylation is regulated by Pim1, a protein kinase of the protoconcogene family. Here, we tested the effects of a selective Pim1 inhibitor (Pim1i), on spatial reference and working memory and AD-like pathology in 3xTg-AD mice. We have identified a Pim1i that crosses the blood brain barrier and reduces PRAS40 phosphorylation. Pim1i-treated 3xTg-AD mice performed significantly better than their vehicle treated counterparts as well as non-transgenic mice. Additionally, 3xTg-AD Pim1i-treated mice showed a reduction in soluble and insoluble Aβ40 and Aβ42 levels, as well as a 45.2 % reduction in Aβ42 plaques within the hippocampus. Furthermore, phosphorylated tau immunoreactivity was reduced in the hippocampus of Pim1i-treated 3xTg-AD mice by 38 %. Mechanistically, these changes were linked to a significant increase in proteasome activity. These results suggest that reductions in phosphorylated PRAS40 levels via Pim1 inhibition reduce Aβ and Tau pathology and rescue cognitive deficits by increasing proteasome function. Given that Pim1 inhibitors are already being tested in ongoing human clinical trials for cancer, the results presented here may open a new venue of drug discovery for AD by developing more Pim1 inhibitors.

Why do family doctors prescribe potentially inappropriate medication to elderly patients?

PubMed

Voigt, Karen; Gottschall, Mandy; Köberlein-Neu, Juliane; Schübel, Jeannine; Quint, Nadine; Bergmann, Antje

2016-07-22

Based on changes in pharmacokinetics and -dynamics in elderly patients, there are potentially inappropriate medications (PIM) that should be avoided in patients aged ≥ 65 years. Current studies showed prescription rates of PIM between 22.5 and 28.4 % in the primary care setting. The evidence concerning reasons for PIM prescription by FPs is limited. This mixed method study consisted of three research parts: 1) semi-standardized content analysis of patients' records, 2) qualitative interviews with FPs using a) open questions and b) selected patient-specific case vignettes and 3) qualitative interviews with FPs' medical assistants. The integration of qualitative interviews was used to explain the quantitative results (triangulation design). PIM were identified according to the German PRISCUS list. Descriptive and multivariate statistical analysis was done using SPSS 22.0. Qualitative content analysis of interviews was used to classify the content of the interviews for indicating pertinent categories. All data were pseudonymously recorded and analyzed. Content analysis of 1846 patients' records and interviews with 7 related FPs were conducted. Elderly patients [n = 1241, mean age: 76, females: 56.6 %] were characterized in average by 8.3 documented chronic diagnosis. 23.9 % of elderly patients received at least one PIM prescription. Sedatives/hypnotics were the most frequent prescribed PIM-drugs (13.7 %). Mental disorders, gender and number of long-term medication were detected as predictors for the probability of a PIM prescription. Common reported reasons for PIM prescription by FPs concerned limited knowledge regarding PIM, limited applicability of PIM lists in daily practice, lack of time, having no alternatives in medication, stronger patient-related factors than age that influence prescription, own bad experiences regarding changes of medication or refusal of following prescriptions of sedative/hypnotics. It is essential to see FPs in a complex decision making situation with several influencing factors on their prescribing, including: patient-oriented prioritization, FPs' experiences in daily practice, FPs' knowledge regarding existing recommendations and their trust in it and organizational characteristics of FPs' daily medical practice. These pros and cons of PIM prescription in elderly patients should be considered in FPs' advanced training.

Tutorial: Reactive high power impulse magnetron sputtering (R-HiPIMS)

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

Anders, André

High Power Impulse Magnetron Sputtering (HiPIMS) is a coating technology that combines magnetron sputtering with pulsed power concepts. Furthermore, by applying power in pulses of high amplitude and a relatively low duty cycle, large fractions of sputtered atoms and near-target gases are ionized. In contrast to conventional magnetron sputtering, HiPIMS is characterized by self-sputtering or repeated gas recycling for high and low sputter yield materials, respectively, and both for most intermediate materials. The dense plasma in front of the target has the dual function of sustaining the discharge and providing plasma-assistance to film growth, affecting the microstructure of growing films.more » Many technologically interesting thin films are compound films, which are composed of one or more metals and a reactive gas, most often oxygen or nitrogen. When reactive gas is added, non-trivial consequences arise for the system because the target may become “poisoned,” i.e., a compound layer forms on the target surface affecting the sputtering yield and the yield of secondary electron emission and thereby all other parameters. It is emphasized that the target state depends not only on the reactive gas' partial pressure (balanced via gas flow and pumping) but also on the ion flux to the target, which can be controlled by pulse parameters. This is a critical technological opportunity for reactive HiPIMS (R-HiPIMS). The scope of this tutorial is focused on plasma processes and mechanisms of operation and only briefly touches upon film properties. It introduces R-HiPIMS in a systematic, step-by-step approach by covering sputtering, magnetron sputtering, reactive magnetron sputtering, pulsed reactive magnetron sputtering, HiPIMS, and finally R-HiPIMS. The tutorial is concluded by considering variations of R-HiPIMS known as modulated pulsed power magnetron sputtering and deep-oscillation magnetron sputtering and combinations of R-HiPIMS with superimposed dc magnetron sputtering.« less

General practitioners' views on (long-term) prescription and use of problematic and potentially inappropriate medication for oldest-old patients-A qualitative interview study with GPs (CIM-TRIAD study).

PubMed

Pohontsch, Nadine Janis; Heser, Kathrin; Löffler, Antje; Haenisch, Britta; Parker, Debora; Luck, Tobias; Riedel-Heller, Steffi G; Maier, Wolfgang; Jessen, Frank; Scherer, Martin

2017-02-17

Potentially inappropriate medication (PIM) is defined as medication with uncertain therapeutic effects and/or potential adverse drug reactions outweighing the clinical benefits. The prescription rate of PIM for oldest-old patients is high despite the existence of lists of PIM (e.g. the PRISCUS list) and efforts to raise awareness. This study aims at identifying general practitioners' views on PIM and aspects affecting the (long-term) use of PIM. As part of the CIM-TRIAD study, we conducted semi-structured, qualitative interviews with 47 general practitioners, discussing 25 patients with and 22 without PIM (according to the PRISCUS list). The interview guideline included generic and patient-specific questions. Interviews were digitally recorded and transcribed verbatim. We content analyzed the interviews using deductive and inductive category development. The majority of the general practitioners were not aware of the PRISCUS list. Agents deemed potentially inappropriate from the general practitioners' point of view and the PRISCUS list are not completely superimposable. General practitioners named their criteria to identify appropriate medication for elderly patients (e.g. renal function, cognitive state) and emphasized the importance of monitoring. We identified prescription- (e.g. benzodiazepines on alternative private prescription), medication- (e.g. subjective perception that PIM has no alternative), general practitioner- (e.g. general practitioner relies on specialists), patient- (e.g. "demanding high-user", positive subjective benefit-risk-ratio) and system-related aspects (e.g. specialists lacking holistic view, interface problems) related to the (long term) use of PIM. While the PRISCUS list does not seem to play a decisive role in general practice, general practitioners are well aware of risks associated with PIM. Our study identifies some starting points for a safer handling of PIM, e.g. stronger dissemination of the PRISCUS list, better compensation of medication reviews, "positive lists", adequate patient information, multifaceted interventions and improved communication between general practitioners and specialists.

Tutorial: Reactive high power impulse magnetron sputtering (R-HiPIMS)

DOE PAGES

Anders, André

2017-03-21

High Power Impulse Magnetron Sputtering (HiPIMS) is a coating technology that combines magnetron sputtering with pulsed power concepts. Furthermore, by applying power in pulses of high amplitude and a relatively low duty cycle, large fractions of sputtered atoms and near-target gases are ionized. In contrast to conventional magnetron sputtering, HiPIMS is characterized by self-sputtering or repeated gas recycling for high and low sputter yield materials, respectively, and both for most intermediate materials. The dense plasma in front of the target has the dual function of sustaining the discharge and providing plasma-assistance to film growth, affecting the microstructure of growing films.more » Many technologically interesting thin films are compound films, which are composed of one or more metals and a reactive gas, most often oxygen or nitrogen. When reactive gas is added, non-trivial consequences arise for the system because the target may become “poisoned,” i.e., a compound layer forms on the target surface affecting the sputtering yield and the yield of secondary electron emission and thereby all other parameters. It is emphasized that the target state depends not only on the reactive gas' partial pressure (balanced via gas flow and pumping) but also on the ion flux to the target, which can be controlled by pulse parameters. This is a critical technological opportunity for reactive HiPIMS (R-HiPIMS). The scope of this tutorial is focused on plasma processes and mechanisms of operation and only briefly touches upon film properties. It introduces R-HiPIMS in a systematic, step-by-step approach by covering sputtering, magnetron sputtering, reactive magnetron sputtering, pulsed reactive magnetron sputtering, HiPIMS, and finally R-HiPIMS. The tutorial is concluded by considering variations of R-HiPIMS known as modulated pulsed power magnetron sputtering and deep-oscillation magnetron sputtering and combinations of R-HiPIMS with superimposed dc magnetron sputtering.« less

Tutorial: Reactive high power impulse magnetron sputtering (R-HiPIMS)

NASA Astrophysics Data System (ADS)

Anders, André

2017-05-01

High Power Impulse Magnetron Sputtering (HiPIMS) is a coating technology that combines magnetron sputtering with pulsed power concepts. By applying power in pulses of high amplitude and a relatively low duty cycle, large fractions of sputtered atoms and near-target gases are ionized. In contrast to conventional magnetron sputtering, HiPIMS is characterized by self-sputtering or repeated gas recycling for high and low sputter yield materials, respectively, and both for most intermediate materials. The dense plasma in front of the target has the dual function of sustaining the discharge and providing plasma-assistance to film growth, affecting the microstructure of growing films. Many technologically interesting thin films are compound films, which are composed of one or more metals and a reactive gas, most often oxygen or nitrogen. When reactive gas is added, non-trivial consequences arise for the system because the target may become "poisoned," i.e., a compound layer forms on the target surface affecting the sputtering yield and the yield of secondary electron emission and thereby all other parameters. It is emphasized that the target state depends not only on the reactive gas' partial pressure (balanced via gas flow and pumping) but also on the ion flux to the target, which can be controlled by pulse parameters. This is a critical technological opportunity for reactive HiPIMS (R-HiPIMS). The scope of this tutorial is focused on plasma processes and mechanisms of operation and only briefly touches upon film properties. It introduces R-HiPIMS in a systematic, step-by-step approach by covering sputtering, magnetron sputtering, reactive magnetron sputtering, pulsed reactive magnetron sputtering, HiPIMS, and finally R-HiPIMS. The tutorial is concluded by considering variations of R-HiPIMS known as modulated pulsed power magnetron sputtering and deep-oscillation magnetron sputtering and combinations of R-HiPIMS with superimposed dc magnetron sputtering.

The Inhibition of Aluminum Corrosion in Sulfuric Acid by Poly(1-vinyl-3-alkyl-imidazolium Hexafluorophosphate).

PubMed

Arellanes-Lozada, Paulina; Olivares-Xometl, Octavio; Guzmán-Lucero, Diego; Likhanova, Natalya V; Domínguez-Aguilar, Marco A; Lijanova, Irina V; Arce-Estrada, Elsa

2014-08-07

Compounds of poly(ionic liquid)s (PILs), derived from imidazole with different alkylic chain lengths located in the third position of the imidazolium ring (poly(1-vinyl-3-dodecyl-imidazolium) (PImC 12 ), poly(1-vinyl-3-octylimidazolium) (PImC₈) and poly(1-vinyl-3-butylimidazolium) (PImC₄) hexafluorophosphate) were synthesized. These compounds were tested as corrosion inhibitors on aluminum alloy AA6061 in diluted sulfuric acid (0.1-1 M H₂SO₄) by weight loss tests, polarization resistance measurements and inductively coupled plasma optical emission spectroscopy. Langmuir's isotherms suggested film formation on bare alloy while standard free energy indicated inhibition by a physisorption process. However, compound efficiencies as inhibitors ranked low (PImC 12 > PImC₈ > PImC₄) to reach 61% for PImC 12 in highly diluted acidic solution. Apparently, the high mobility of sulfates favored their adsorption in comparison to PILs. The surface film displayed general corrosion, and pitting occurred as a consequence of PILs' partial inhibition along with a continuous dissolution of defective patchy film on formation. A slight improvement in efficiency was displayed by compounds having high molecular weight and a long alkyl chain, as a consequence of steric hindrance and PIL interactions.

Molecular Control of Polyene Macrolide Biosynthesis

PubMed Central

Santos-Aberturas, Javier; Vicente, Cláudia M.; Guerra, Susana M.; Payero, Tamara D.; Martín, Juan F.; Aparicio, Jesús F.

2011-01-01

Control of polyene macrolide production in Streptomyces natalensis is mediated by the transcriptional activator PimM. This regulator, which combines an N-terminal PAS domain with a C-terminal helix-turn-helix motif, is highly conserved among polyene biosynthetic gene clusters. PimM, truncated forms of the protein without the PAS domain (PimMΔPAS), and forms containing just the DNA-binding domain (DBD) (PimMDBD) were overexpressed in Escherichia coli as GST-fused proteins. GST-PimM binds directly to eight promoters of the pimaricin cluster, as demonstrated by electrophoretic mobility shift assays. Assays with truncated forms of the protein revealed that the PAS domain does not mediate specificity or the distinct recognition of target genes, which rely on the DBD domain, but significantly reduces binding affinity up to 500-fold. Transcription start points were identified by 5′-rapid amplification of cDNA ends, and the binding regions of PimMDBD were investigated by DNase I protection studies. In all cases, binding took place covering the −35 hexamer box of each promoter, suggesting an interaction of PimM and RNA polymerase to cause transcription activation. Information content analysis of the 16 sequences protected in target promoters was used to deduce the structure of the PimM-binding site. This site displays dyad symmetry, spans 14 nucleotides, and adjusts to the consensus TVGGGAWWTCCCBA. Experimental validation of this binding site was performed by using synthetic DNA duplexes. Binding of PimM to the promoter region of one of the polyketide synthase genes from the Streptomyces nodosus amphotericin cluster containing the consensus binding site was also observed, thus proving the applicability of the findings reported here to other antifungal polyketides. PMID:21187288

Spatial interaction between tissue pressure and skeletal muscle perfusion during contraction.

PubMed

van Donkelaar, C C; Huyghe, J M; Vankan, W J; Drost, M R

2001-05-01

The vascular waterfall theory attributes decreased muscle perfusion during contraction to increased intramuscular pressure (P(IM)) and concomitant increase in venous resistance. Although P(IM) is distributed during contractions, this theory does not account for heterogeneity. This study hypothesises that pressure heterogeneity could affect the interaction between P(IM) rise and perfusion. Regional tissue perfusion during submaximum (100kPa) tetanic contraction is studied, using a finite element model of perfused contracting skeletal muscle. Capillary flow in muscles with one proximal artery and vein (SIM(1)) and with an additional distal artery and vein (SIM(2)) is compared. Blood flow and pressures at rest and P(IM) during contraction ( approximately 25kPa maximally) are similar between simulations, but capillary flow and venous pressure differ. In SIM(2), venous pressure and capillary flow correspond to P(IM) distribution, whereas capillary flow in SIM(1) is less than 10% of flow in SIM(2), in the muscle half without draining vein. This difference is caused by a high central P(IM), followed by central venous pressure rise, in agreement with the waterfall theory. The high central pressure (SIM(1)), obstructs outflow from the distal veins. Distal venous pressure rises until central blood pressure is reached, although local P(IM) is low. Adding a distal vein (SIM(2)) restores the perfusion. It is concluded that regional effects contribute to the interaction between P(IM) and perfusion during contraction. Unlike stated by the vascular waterfall theory, venous pressure may locally exceed P(IM). Although this can be explained by the principles of this theory, the theory does not include this phenomenon as such.

Prescribing potentially inappropriate medication (PIM) in Germany's elderly as indicated by the PRISCUS list. An analysis based on regional claims data.

PubMed

Schubert, Ingrid; Küpper-Nybelen, Jutta; Ihle, Peter; Thürmann, Petra

2013-07-01

The aim of this study was to estimate the prevalence of potentially inappropriate medication (PIM) in the elderly as indicated by Germany's recently published list (PRISCUS) and to assess factors independently associated with PIM prescribing, both overall and separately for therapeutic groups. Claims data analysis (Health Insurance Sample AOK Hesse/KV Hesse, 18.75% random sample of insurants from AOK Hesse, Germany) is used in the study. The study population is composed of 73,665 insurants >64 years of age continuously insured in the last quarter of 2009 and either continuously insured or deceased in 2010. Prevalence estimates are standardized to the population of Germany (31 December 2010). The variables age, sex, polypharmacy, hospital stay and nursing care are assessed for their independent association with general PIM prescription and among 11 therapeutic subgroups using multivariate logistic regression analysis. In 2010, 22.0% of the elderly received at least one PIM prescription (men: 18.3%, women: 24.8%). The highest PIM prevalence was observed for antidepressants (6.5%), antihypertensives (3.8%) and antiarrhythmic drugs (3.5%). Amitriptyline, tetrazepam, doxepin, acetyldigoxin, doxazosin and etoricoxib were the most frequently prescribed PIMs. Multivariate analyses indicate that women (OR 1.39; 95% CI: 1.34-1.44) and persons with extreme polypharmacy (≥10 vs. <5 drugs: OR 5.16; 95% CI: 4.87-5.47) were at higher risk for receiving a PRISCUS-PIM. Risk analysis for therapeutic groups shows divergent associations. PRISCUS-PIMs are widely used. Educational programs should focus on drugs with high treatment prevalence and call professionals' attention to those elderly patients who are at special risk for inappropriate medication. Copyright © 2013 John Wiley & Sons, Ltd.

Performance Information Management System (PIMS) Communication

DTIC Science & Technology

1993-12-31

34AD-A284 851 AD MIPR NO. MIPR 92MM2501 TITLE: Performance Information Management System (PIMS) Communication PRINCIPAL INVESTIGATOR: Kathryn P...93 . . ..- F •nal,. 12/1/91 - 12/31/93- ...... . ..... PIMS-Performance Information Management System Communications 92MM2501 Kathryn P. Winter Navy

How Much Do Ultrathin Polymers with Intrinsic Microporosity Swell in Liquids?

PubMed

Ogieglo, Wojciech; Ghanem, Bader; Ma, Xiaohua; Pinnau, Ingo; Wessling, Matthias

2016-10-06

As synthetic membrane materials, polymers with intrinsic microporosity (PIMs) have demonstrated unprecedented permeation and molecular-separation properties. Here, we report the swelling characteristics of submicron-thick supported films of spirobisindane-based PIMs, PIM-1 and PIM-6FDA-OH, for six organic solvents and water using in situ spectroscopic ellipsometry. Surprisingly, PIMs swell significantly in most organic solvents, with swelling factors (SF = h swollen /h dry ) as high as 2.5. This leads to the loss of the ultrarigid character of the polymer and produces equilibrated liquid-like swollen films. Filling of the excess frozen-in fractional free volume with liquid was discovered next to swelling-induced polymer matrix dilation. Water hardly swells the polymer matrix, but it penetrates into the intrinsic microporous structure. This study is the first to provide fundamental swelling data for PIMs, leading to better comprehension of their permeation properties. Such an understanding is indispensable for applications such as solvent filtration, natural-gas separation, and ion retention in flow batteries.

Increased expression of activated pSTAT3 and PIM-1 in the pulmonary vasculature of experimental congenital diaphragmatic hernia.

PubMed

Hofmann, Alejandro D; Takahashi, Toshiaki; Duess, Johannes; Gosemann, Jan-Hendrik; Puri, Prem

2015-06-01

Signal transducer and activator of transcription (STAT) protein family (STAT1-6) regulates diverse cellular processes. Recently, the isoform STAT3 has been implicated to play a central role in the pathogenesis of pulmonary hypertension (PH). In human PH activated STAT3 (pSTAT3) was shown to directly trigger expression of the provirus integration site for Moloney murine leukemia virus (Pim-1), which promotes proliferation and resistance to apoptosis in SMCs. We designed this study to investigate the hypothesis that pSTAT3 and Pim-1 pulmonary vascular expression is increased in nitrofen-induced CDH. Pregnant rats were exposed to nitrofen or vehicle on D9.5. Fetuses were sacrificed on D21 and divided into nitrofen (n=16) and control group (n=16). QRT-PCR, western blotting, and confocal-immunofluorescence were performed to determine pulmonary gene and protein expression levels of pSTAT3 and Pim-1. Pulmonary Pim-1 gene expression was significantly increased in the CDH group compared to controls. Western blotting and confocal-microscopy confirmed increased pulmonary protein expression of Pim-1 and increased activation of pSTAT3 in CDH lungs compared to controls. Markedly increased gene and protein expression of Pim-1 and activated pSTAT3 in the pulmonary vasculature of nitrofen-induced CDH lungs suggest that pSTAT3 and Pim-1 are important mediators of PH in nitrofen-induced CDH. Copyright © 2015. Published by Elsevier Inc.

RSK2 is a new Pim2 target with pro-survival functions in FLT3-ITD-positive acute myeloid leukemia.

PubMed

Hospital, M-A; Jacquel, A; Mazed, F; Saland, E; Larrue, C; Mondesir, J; Birsen, R; Green, A S; Lambert, M; Sujobert, P; Gautier, E-F; Salnot, V; Le Gall, M; Decroocq, J; Poulain, L; Jacque, N; Fontenay, M; Kosmider, O; Récher, C; Auberger, P; Mayeux, P; Bouscary, D; Sarry, J-E; Tamburini, J

2018-03-01

Acute myeloid leukemia (AML) with the FLT3 internal tandem duplication (FLT3-ITD AML) accounts for 20-30% of AML cases. This subtype usually responds poorly to conventional therapies, and might become resistant to FLT3 tyrosine kinase inhibitors (TKIs) due to molecular bypass mechanisms. New therapeutic strategies focusing on resistance mechanisms are therefore urgently needed. Pim kinases are FLT3-ITD oncogenic targets that have been implicated in FLT3 TKI resistance. However, their precise biological function downstream of FLT3-ITD requires further investigation. We performed high-throughput transcriptomic and proteomic analyses in Pim2-depleted FLT3-ITD AML cells and found that Pim2 predominantly controlled apoptosis through Bax expression and mitochondria disruption. We identified ribosomal protein S6 kinase A3 (RSK2), a 90 kDa serine/threonine kinase involved in the mitogen-activated protein kinase cascade encoded by the RPS6KA3 gene, as a novel Pim2 target. Ectopic expression of an RPS6KA3 allele rescued the viability of Pim2-depleted cells, supporting the involvement of RSK2 in AML cell survival downstream of Pim2. Finally, we showed that RPS6KA3 knockdown reduced the propagation of human AML cells in vivo in mice. Our results point to RSK2 as a novel Pim2 target with translational therapeutic potential in FLT3-ITD AML.

Processor-In-Memory (PIM) Based Architectures for PetaFlops Potential Massively Parallel Processing

NASA Technical Reports Server (NTRS)

Kogge, Peter M.

1996-01-01

The report summarizes the work performed at the University of Notre Dame under a NASA grant from July 15, 1995 through July 14, 1996. Researchers involved in the work included the PI, Dr. Peter M. Kogge, and three graduate students under his direction in the Computer Science and Engineering Department: Stephen Dartt, Costin Iancu, and Lakshmi Narayanaswany. The organization of this report is as follows. Section 2 is a summary of the problem addressed by this work. Section 3 is a summary of the project's objectives and approach. Section 4 summarizes PIM technology briefly. Section 5 overviews the main results of the work. Section 6 then discusses the importance of the results and future directions. Also attached to this report are copies of several technical reports and publications whose contents directly reflect results developed during this study.

Performance Information Management System (PIMS) Communication

DTIC Science & Technology

1992-10-15

AD-A267 040 AD 14IPR NO: 92M•2501 TITLE: PERFORMANCE INFORMATION MANAGEMENT SYSTEM (PIMS) COMMUNICATION V G ,c¶• PRINCIPAL INVESTIGATOR: Kathryn P...Performance Information Management System (PIMS) MIPR No. Communication 92MM2501 6. AUTHOR(S) Kathryn P. Winter 7. PERFORMING ORGANIZATION NAME(S) AND

Overcoming Resistance to Inhibitors of the Akt Protein Kinase by Modulation of the Pim Kinase Pathway

DTIC Science & Technology

2017-01-01

regulated by Pim and what is the outcome of treating animals with Pim inhibitors. To explore these tasks we first stained human tumor and normal samples ...Sepharose beads. The beads were incubated with 100 ng of purified Pim-1 proteins at 37 °C for 30 minutes. Samples were analyzed by immunoblot assays using...secreted by these cells using novel technology, develop potential urine biomarkers of treatment success. 1R21 CA178324-01A1 (Kraft, PI) 06/01/15

Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase.

PubMed

Fischer, Kimberlee M; Cottage, Christopher T; Wu, Weitao; Din, Shabana; Gude, Natalie A; Avitabile, Daniele; Quijada, Pearl; Collins, Brett L; Fransioli, Jenna; Sussman, Mark A

2009-11-24

Despite numerous studies demonstrating the efficacy of cellular adoptive transfer for therapeutic myocardial regeneration, problems remain for donated cells with regard to survival, persistence, engraftment, and long-term benefits. This study redresses these concerns by enhancing the regenerative potential of adoptively transferred cardiac progenitor cells (CPCs) via genetic engineering to overexpress Pim-1, a cardioprotective kinase that enhances cell survival and proliferation. Intramyocardial injections of CPCs overexpressing Pim-1 were given to infarcted female mice. Animals were monitored over 4, 12, and 32 weeks to assess cardiac function and engraftment of Pim-1 CPCs with echocardiography, in vivo hemodynamics, and confocal imagery. CPCs overexpressing Pim-1 showed increased proliferation and expression of markers consistent with cardiogenic lineage commitment after dexamethasone exposure in vitro. Animals that received CPCs overexpressing Pim-1 also produced greater levels of cellular engraftment, persistence, and functional improvement relative to control CPCs up to 32 weeks after delivery. Salutary effects include reduction of infarct size, greater number of c-kit(+) cells, and increased vasculature in the damaged region. Myocardial repair is significantly enhanced by genetic engineering of CPCs with Pim-1 kinase. Ex vivo gene delivery to enhance cellular survival, proliferation, and regeneration may overcome current limitations of stem cell-based therapeutic approaches.

The Inhibition of Aluminum Corrosion in Sulfuric Acid by Poly(1-vinyl-3-alkyl-imidazolium Hexafluorophosphate)

PubMed Central

Arellanes-Lozada, Paulina; Olivares-Xometl, Octavio; Guzmán-Lucero, Diego; Likhanova, Natalya V.; Domínguez-Aguilar, Marco A.; Lijanova, Irina V.; Arce-Estrada, Elsa

2014-01-01

Compounds of poly(ionic liquid)s (PILs), derived from imidazole with different alkylic chain lengths located in the third position of the imidazolium ring (poly(1-vinyl-3-dodecyl-imidazolium) (PImC12), poly(1-vinyl-3-octylimidazolium) (PImC8) and poly(1-vinyl-3-butylimidazolium) (PImC4) hexafluorophosphate) were synthesized. These compounds were tested as corrosion inhibitors on aluminum alloy AA6061 in diluted sulfuric acid (0.1–1 M H2SO4) by weight loss tests, polarization resistance measurements and inductively coupled plasma optical emission spectroscopy. Langmuir’s isotherms suggested film formation on bare alloy while standard free energy indicated inhibition by a physisorption process. However, compound efficiencies as inhibitors ranked low (PImC12 > PImC8 > PImC4) to reach 61% for PImC12 in highly diluted acidic solution. Apparently, the high mobility of sulfates favored their adsorption in comparison to PILs. The surface film displayed general corrosion, and pitting occurred as a consequence of PILs’ partial inhibition along with a continuous dissolution of defective patchy film on formation. A slight improvement in efficiency was displayed by compounds having high molecular weight and a long alkyl chain, as a consequence of steric hindrance and PIL interactions. PMID:28788156

Synthesis and Transport Properties of Novel MOF/PIM-1/MOF Sandwich Membranes for Gas Separation

PubMed Central

Fuoco, Alessio; Khdhayyer, Muhanned R.; Attfield, Martin P.; Esposito, Elisa; Jansen, Johannes C.; Budd, Peter M.

2017-01-01

Metal-organic frameworks (MOFs) were supported on polymer membrane substrates for the fabrication of composite polymer membranes based on unmodified and modified polymer of intrinsic microporosity (PIM-1). Layers of two different MOFs, zeolitic imidazolate framework-8 (ZIF-8) and Copper benzene tricarboxylate ((HKUST-1), were grown onto neat PIM-1, amide surface-modified PIM-1 and hexamethylenediamine (HMDA) -modified PIM-1. The surface-grown crystalline MOFs were characterized by a combination of several techniques, including powder X-ray diffraction, infrared spectroscopy and scanning electron microscopy to investigate the film morphology on the neat and modified PIM-1 membranes. The pure gas permeabilities of He, H2, O2, N2, CH4, CO2 were studied to understand the effect of the surface modification on the basic transport properties and evaluate the potential use of these membranes for industrially relevant gas separations. The pure gas transport was discussed in terms of permeability and selectivity, highlighting the effect of the MOF growth on the diffusion coefficients of the gas in the new composite polymer membranes. The results confirm that the growth of MOFs on polymer membranes can enhance the selectivity of the appropriately functionalized PIM-1, without a dramatic decrease of the permeability. PMID:28208658

Knowledge Translation Strategy to Reduce the Use of Potentially Inappropriate Medications in Hospitalized Elderly Adults.

PubMed

Cossette, Benoit; Bergeron, Josée; Ricard, Geneviève; Éthier, Jean-François; Joly-Mischlich, Thomas; Levine, Mitchell; Sene, Modou; Mallet, Louise; Lanthier, Luc; Payette, Hélène; Rodrigue, Marie-Claude; Brazeau, Serge

2016-12-01

To evaluate the effect of a knowledge translation (KT) strategy to reduce potentially inappropriate medication (PIM) use in hospitalized elderly adults. Segmented regression analysis of an interrupted time series. Teaching hospital. Individuals aged 75 and older discharged from the hospital in 2013/14 (mean age 83.3, 54.5% female). The KT strategy comprises the distribution of educational materials, presentations by geriatricians, pharmacist-physician interventions based on alerts from a computerized alert system, and comprehensive geriatric assessments. Rate of PIM use (number of patient-days with use of at least one PIM/number of patient-days of hospitalization for individuals aged ≥75). For 8,622 patients with 14,071 admissions, a total of 145,061 patient-days were analyzed. One or more PIMs were prescribed on 28,776 (19.8%) patient-days; a higher rate was found for individuals aged 75 to 84 (24.0%) than for those aged 85 and older (14.4%) (P < .001), and in women (20.8%) than in men (18.6%) (P < .001). The drug classes most frequently accounting for the PIM were gastrointestinal agents (21%), antihistamines (18%), and antidepressants (17%). An absolute decrease of 3.5% (P < .001) of patient-days with at least one PIM was observed immediately after the intervention. A KT strategy resulted in decreased use of PIM in elderly adults in the hospital. Additional interventions will be implemented to maintain or further reduce PIM use. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes.

PubMed

Mumenthaler, Shannon M; Ng, Patricia Y B; Hodge, Amanda; Bearss, David; Berk, Gregory; Kanekal, Sarath; Redkar, Sanjeev; Taverna, Pietro; Agus, David B; Jain, Anjali

2009-10-01

The serine/threonine family of Pim kinases function as oncogenes and have been implicated in prostate cancer progression, particularly in hormone-refractory prostate disease, as a result of their antiapoptotic function. In this study, we used a pharmacologic inhibitor targeting the Pim family members, SGI-1776, to determine whether modulation of Pim kinase activity could alter prostate cancer cell survival and modulate chemotherapy resistance. Extensive biochemical characterization of SGI-1776 confirmed its specificity for the three isoforms of the Pim family. Treatment of prostate cancer cells with SGI-1776 resulted in a dose-dependent reduction in phosphorylation of known Pim kinase substrates that are involved in cell cycle progression and apoptosis (p21(Cip1/WAF1) and Bad). Consequently, SGI-1776 compromised overall cell viability by inducing G(1) cell cycle arrest and triggering apoptosis. Overexpression of recombinant Pim-1 markedly increased sensitivity of SGI-1776-mediated prostate cancer cell apoptosis and p21(Cip1/WAF1) phosphorylation inhibition, reinforcing the specificity of SGI-1776. An additional cytotoxic effect was observed when SGI-1776 was combined with taxane-based chemotherapy agents. SGI-1776 was able to reduce cell viability in a multidrug resistance 1 protein-based taxane-refractory prostate cancer cell line. In addition, SGI-1776 treatment was able to resensitize chemoresistant cells to taxane-based therapies by inhibiting multidrug resistance 1 activity and inducing apoptosis. These findings support the idea that inhibiting Pim kinases, in combination with a chemotherapeutic agent, could play an important role in prostate cancer treatment by targeting the clinical problem of chemoresistance.

Anomalies in the low frequency vibrational density of states for a polymer with intrinsic microporosity - the Boson peak of PIM-1.

PubMed

Zorn, Reiner; Yin, Huajie; Lohstroh, Wiebke; Harrison, Wayne; Budd, Peter M; Pauw, Brian R; Böhning, Martin; Schönhals, Andreas

2018-01-17

Polymers with intrinsic microporosity are promising candidates for the active separation layer in gas separation membranes. Here, the vibrational density of states (VDOS) for PIM-1, the prototypical polymer with intrinsic microporosity, is investigated by means of inelastic neutron scattering. The results are compared to data measured for a more conventional high-performance polyimide used in gas separation membranes (Matrimid). The measured data show the characteristic low frequency excess contribution to VDOS above the Debye sound wave level, generally known as the Boson peak in glass-forming materials. In comparison to the Boson peak of Matrimid, that of PIM-1 is shifted to lower frequencies. This shift is discussed considering the microporous, sponge-like structure of PIM-1 as providing a higher compressibility at the molecular scale than for conventional polymers. For an annealed PIM-1 sample, the Boson peak shifts to higher frequencies in comparison to the un-annealed sample. These changes in the VDOS of the annealed PIM-1 sample are related to changes in the microporous structure as confirmed by X-ray scattering.

Exact nonstationary responses of rectangular thin plate on Pasternak foundation excited by stochastic moving loads

NASA Astrophysics Data System (ADS)

Chen, Guohai; Meng, Zeng; Yang, Dixiong

2018-01-01

This paper develops an efficient method termed as PE-PIM to address the exact nonstationary responses of pavement structure, which is modeled as a rectangular thin plate resting on bi-parametric Pasternak elastic foundation subjected to stochastic moving loads with constant acceleration. Firstly, analytical power spectral density (PSD) functions of random responses for thin plate are derived by integrating pseudo excitation method (PEM) with Duhamel's integral. Based on PEM, the new equivalent von Mises stress (NEVMS) is proposed, whose PSD function contains all cross-PSD functions between stress components. Then, the PE-PIM that combines the PEM with precise integration method (PIM) is presented to achieve efficiently stochastic responses of the plate by replacing Duhamel's integral with the PIM. Moreover, the semi-analytical Monte Carlo simulation is employed to verify the computational results of the developed PE-PIM. Finally, numerical examples demonstrate the high accuracy and efficiency of PE-PIM for nonstationary random vibration analysis. The effects of velocity and acceleration of moving load, boundary conditions of the plate and foundation stiffness on the deflection and NEVMS responses are scrutinized.

Potentially inappropriate medications in elderly Japanese patients: effects of pharmacists' assessment and intervention based on Screening Tool of Older Persons' Potentially Inappropriate Prescriptions criteria ver.2.

PubMed

Kimura, T; Ogura, F; Yamamoto, K; Uda, A; Nishioka, T; Kume, M; Makimoto, H; Yano, I; Hirai, M

2017-04-01

The Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (stopp) criteria were updated in 2014 (stopp criteria ver.2), but few studies have evaluated the usefulness of stopp criteria in elderly patients. This prospective observational study evaluated the prevalence of potentially inappropriate medications (PIMs), and the efficacy of hospital pharmacists' assessment and intervention based on stopp criteria ver.2. The study was conducted at three medical units of Kobe University Hospital between April 2015 and March 2016. Pharmacists assessed and detected PIMs based on stopp criteria ver.2 and considered the patient's intention to change the prescription at the time of admission of each patient. If the pharmacists judged that benefits outweighed risks of prescription change and the patients consented to change the medications, they recommended the doctor to change the prescription. If there was a risk of exacerbation of disease by the change of medications and the pharmacists judged it to be difficult to adjust medications during hospitalization or the patients did not consent to change the medications, they did not recommend to change it. The pharmacists and the doctors discussed and finally decided whether to change the PIMs or not. The number of patients prescribed PIMs, the number and contents of PIMs, and the number of medications changed after pharmacists' intervention were calculated. Totally, 822 new inpatients aged ≥65 years prescribed ≥1 daily medicine were included. Their median (interquartile range) age was 75·0 (71·0-80·0) years, and 54·9% were male. According to the criteria, 346 patients (42·1%) were prescribed ≥1 PIMs. Patients prescribed PIMs took significantly more medications than others: 10·0 (7·0-13·0) vs. 6·0 (4·0-9·0), P < 0·001. The total number of PIMs was 651%, 47·6% of which (n = 310) were recommended the doctors to change, and 292 of 651 PIMs (44·9%) were finally discontinued/changed after pharmacists' assessment and intervention. PIMs related to benzodiazepines, including Z-drugs, were most frequent, with a detailed classifications as follows (changed/total): (i) benzodiazepines for 4 or more weeks (75/205), (ii) drugs that predictably increase the risk of falls in older people (benzodiazepines) (30/67) and (iii) drugs that predictably increase the risk of falls in older people (hypnotic Z-drugs) (15/31). Over 40% elderly patients were prescribed PIMs, and pharmacists' assessments and interventions based on stopp criteria ver.2 were useful in detecting and correcting prescription of PIMs. © 2016 John Wiley & Sons Ltd.

PIM Pedagogy: Toward a Loosely Unified Model for Teaching and Studying Comics and Graphic Novels

ERIC Educational Resources Information Center

Carter, James B.

2015-01-01

The article debuts and explains "PIM" pedagogy, a construct for teaching comics at the secondary- and post-secondary levels and for deep reading/studying comics. The PIM model for considering comics is actually based in major precepts of education studies, namely constructivist foundations of learning, and loosely unifies constructs…

The User-Subjective Approach to Personal Information Management Systems.

ERIC Educational Resources Information Center

Bergman, Ofer; Beyth-Marom, Ruth; Nachmias, Rafi

2003-01-01

Explains personal information management (PIM) systems and suggests a user-subjective approach to PIM system design. Advocates that PIM systems relate to the subjective value-added attributes that the user gives the stored data so that the user can find information again, recall it when needed, and use it effectively in the next interaction.…

Time of flight in MUSE at PIM1 at Paul Scherrer Institute

NASA Astrophysics Data System (ADS)

Lin, Wan; Gilman, Ronald; MUSE Collaboration

2016-09-01

The MUSE experiment at PIM1 at Paul Scherrer Institute in Villigen, Switzerland, measures elastic scattering of electrons and muons from a liquid hydrogen target. The intent of the experiment is to deduce whether the radius of the proton is the same when determined from the two different particle types. Precision timing is an important aspect of the experiment, used to determine particle types, reaction types, and beam momentum. Here we present results for a test setup measuring time of flight between prototypes of two detector systems to be used in the experiment, compared to Geant4 simulations. The results demonstrate time of flight resolution better than 100 ps, and beam momentum determination at the level of a few tenths of a percent. Douglass Project for Rutgers Women in Math, Science & Engineering, National Science Foundation Grant 1306126 to Rutgers University.

Combination of PIM and JAK2 inhibitors synergistically suppresses cell proliferation and overcomes drug resistance of myeloproliferative neoplasms

PubMed Central

Greco, Rita; Li, Zhifang; Sun, Fangxian; Barberis, Claude; Tabart, Michel; Patel, Vinod; Schio, Laurent; Hurley, Raelene; Chen, Bo; Cheng, Hong; Lengauer, Christoph; Pollard, Jack; Watters, James; Garcia-Echeverria, Carlos; Wiederschain, Dmitri; Adrian, Francisco; Zhang, JingXin

2014-01-01

Inhibitors of JAK2 kinase are emerging as an important treatment modality for myeloproliferative neoplasms (MPN). However, similar to other kinase inhibitors, resistance to JAK2 inhibitors may eventually emerge through a variety of mechanisms. Effective drug combination is one way to enhance therapeutic efficacy and combat resistance against JAK2 inhibitors. To identify potential combination partners for JAK2 compounds in MPN cell lines, we performed pooled shRNA screen targeting 5,000 genes in the presence or absence of JAK2 blockade. One of the top hits identified was MYC, an oncogenic transcription factor that is difficult to inhibit directly, but could be targeted by modulation of upstream regulatory elements such as kinases. We demonstrate herein that PIM kinase inhibitors efficiently suppress MYC protein levels in MPN cell lines. Overexpression of MYC restores the viability of PIM inhibitor-treated cells, revealing causal relationship between MYC down-regulation and cell growth inhibition by PIM compounds. Combination of various PIM inhibitors with a JAK2 inhibitor results in significant synergistic growth inhibition of multiple MPN cancer cell lines and induction of apoptosis. Mechanistic studies revealed strong downregulation of phosphorylated forms of S6 and 4EBP1 by JAK2/PIM inhibitor combination treatment. Finally, such combination was effective in eradicating in vitro JAK2 inhibitor-resistant MPN clones, where MYC is consistently up-regulated. These findings demonstrate that simultaneous suppression of JAK2 and PIM kinase activity by small molecule inhibitors is more effective than either agent alone in suppressing MPN cell growth. Our data suggest that JAK2 and PIM combination might warrant further investigation for the treatment of JAK2-driven hematologic malignancies. PMID:24830942

INFARCT DENSITY DISTRIBUTION BY MRI IN THE PORCINE MODEL OF ACUTE AND CHRONIC MYOCARDIAL INFARCTION AS A POTENTIAL METHOD TRANSFERABLE TO THE CLINIC

PubMed Central

Varga-Szemes, Akos; Simor, Tamas; Lenkey, Zsofia; van der Geest, Rob J; Kirschner, Robert; Toth, Levente; Brott, Brigitta C.; Ada, Elgavish; Elgavish, Gabriel A.

2014-01-01

Purpose To study the feasibility of a myocardial infarct (MI) quantification method (Signal Intensity-based Percent Infarct Mapping, SI-PIM) that is able to evaluate not only the size, but also the density distribution of the MI. Methods In 14 male swine, MI was generated by 90 minutes of closed-chest balloon occlusion followed by reperfusion. Seven (n=7) or 56 (n=7) days after reperfusion, Gd-DTPA-bolus and continuous-infusion enhanced Late Gadolinium Enhancement (LGE) MRI, and R1-mapping were carried out and post mortem triphenyl-tetrazolium-chloride (TTC) staining was performed. MI was quantified using binary (2 or 5 standard deviations, SD), SI-PIM and R1-PIM methods. Infarct Fraction (IF), and Infarct-Involved Voxel Fraction (IIVF) were determined by each MRI method. Bias of each method was compared to the TTC technique. Results The accuracy of MI quantification did not depend on the method of contrast administration or the age of the MI. IFs obtained by either of the two PIM methods were statistically not different from the IFs derived from the TTC measurements at either MI age. IFs obtained from the binary 2SD method overestimated IF obtained from TTC. IIVF among the three different PIM methods did not vary, but with the binary methods the IIVF gradually decreased with increasing the threshold limit. Conclusions The advantage of SI-PIM over the conventional binary method is the ability to represent not only IF but also the density distribution of the MI. Since the SI-PIM methods are based on a single LGE acquisition, the bolus-data-based SI-PIM method can effortlessly be incorporated into the clinical image post-processing procedure. PMID:24718787

The novel anti-adipogenic effect and mechanisms of action of SGI-1776, a Pim-specific inhibitor, in 3T3-L1 adipocytes.

PubMed

Park, Yu-Kyoung; Hong, Victor Sukbong; Lee, Tae-Yoon; Lee, Jinho; Choi, Jong-Soon; Park, Dong-Soon; Park, Gi-Young; Jang, Byeong-Churl

2016-01-01

The proviral integration site for moloney murine leukemia virus (Pim) kinases, consisting of Pim-1, Pim-2 and Pim-3, belongs to a family of serine/threonine kinases that are involved in controlling cell growth and differentiation. Pim kinases are emerging as important mediators of adipocyte differentiation. SGI-1776, an inhibitor of Pim kinases, is widely used to assess the physiological roles of Pim kinases, particularly cell functions. In the present study, we examined the effects of SGI-1776 on adipogenesis. The anti‑adipogenic effect of SGI‑1776 was measured by Oil Red O staining and AdipoRed assays. The effect of SGI‑1776 on the growth of 3T3‑L1 adipocytes was determined by cell count analysis. The effects of SGI‑1776 on the protein and mRNA expression of adipogenesis-related proteins and adipokines in 3T3‑L1 adipocytes were also evaluated by western blot analysis and RT‑PCR, respectively. Notably, SGI-1776 markedly inhibited lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. On a mechanistic level, SGI-1776 inhibited not only the expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ) and fatty acid synthase (FAS), but also the phosphorylation of signal transducer and activator of transcription-3 (STAT-3). Moreover, SGI-1776 decreased the expression of adipokines, including the expression of leptin and regulated on activation, normal T cell expressed and secreted (RANTES) during adipocyte differentiation. These findings demonstrate that SGI-1776 inhibits adipogenesis by downregulating the expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS and STAT-3.

[Gastrointestinal bleeding and potentially inappropriate medication by NSAIDs].

PubMed

Pastor Cano, Josep; Aranda García, Ana; Sánchez Ruiz, José Francisco; Rausell Rausell, Víctor José; Tobaruela Soto, Mariana; Gascón Cánovas, Juan José

2018-05-28

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are widely used but they increase the risk of gastrointestinal haemorrage among other adverse effects. The objective of this study was to compare potentially inappropriate medications (PIM) by NSAIDs using the original Beers Criteria, a global reference for evaluating elderly people's prescriptions, and the Spanish adaptation of the same; and the relation between PIM of NSAIDs and gastrointestinal bleeding. The study was a retrospective observational study carried out located in a primary care district in the province of de Murcia, south-eastern Spain. The study population (n=7.856) were citizens aged 65 and above, with at least one drug prescribed in a Spanish health district during the study period . We analized illnesses and treatments registered in the primary care's electronic medical history of patients and hospital admissions, during the 12 month study period (2012). The original Beers Criteria and their Spanish adaptation were used to evaluate PIM of NSAIDs in patients considering the medication globally and also each active substance. Gastrointestinal bleeding events recorded in the data bases studied were evaluated. Detection of PIM of NSAIDs was 5,6% with the original version and 7,0% (Δ=25,5%; p less than 0,001) with the adapted one. PIM of NSAIDs was related with an increased incidence of gastrointestinal bleeding without significant differences between PIM exposed and NSAID exposed patients AINE (RR=1,6; IC:0,2-14,5). The Spanish adaptation of the Beers criteria identified a greater degree of PIM of NSAIDs than the original version, and in both versions the detection of PIM was not related with a significant increase of gastrointestinal bleeding compared to patients exposed to NSAIDs.

Simulations and experiments on gas adsorption in novel microporous polymers

NASA Astrophysics Data System (ADS)

Larsen, Gregory Steven

Microporous materials represent a fascinating class of materials with a broad range of applications. The work presented here focuses on the use of a novel class of microporous material known as polymers of intrinsic micrioporosity, or PIMs, for use in gas separation and storage technologies. The aim of this research is to develop a detailed understanding of the relationship between the monomeric structure and the adsorptive performance of PIMs. First, a generalizable structure generation technique was developed such that simulation samples of PIM-1 recreated experimental densities, scattering, surface areas, pore size distributions, and adsorption isotherms. After validation, the simulations were applied as virtual experiments on several new PIMs with the intent to screen their capabilities as adsorbent materials and elucidate design principles for linear PIMs. The simulations are useful in understanding the unique properties such as pore size distribution and scattering observed experimentally.

How Do K-12 Students' Manage Applications on Their Mobile Devices?

ERIC Educational Resources Information Center

Aladjem, Ruthi; Hardof, Sharon

2016-01-01

Personal information management (PIM) is a research field that examines the activities by which users save, organize and retrieve personal information items. PIM is a one of the essential new literacies for learners in the 21st century. This paper reports results from a pilot study that explored PIM practices and strategies of K-12 students, on…

High power impulse magnetron sputtering and its applications

NASA Astrophysics Data System (ADS)

Yan, YUAN; Lizhen, YANG; Zhongwei, LIU; Qiang, CHEN

2018-04-01

High power impulse magnetron sputtering (HiPIMS) has attracted a great deal of attention because the sputtered material is highly ionized during the coating process, which has been demonstrated to be advantageous for better quality coating. Therefore, the mechanism of the HiPIMS technique has recently been investigated. In this paper, the current knowledge of HiPIMS is described. We focus on the mechanical properties of the deposited thin film in the latest applications, including hard coatings, adhesion enhancement, tribological performance, and corrosion protection layers. A description of the electrical, optical, photocatalytic, and functional coating applications are presented. The prospects for HiPIMS are also discussed in this work.

T-18, a stemonamide synthetic intermediate inhibits Pim kinase activity and induces cell apoptosis, acting as a potent anticancer drug.

PubMed

Wang, Zhen; Li, Xing-Min; Shang, Kun; Zhang, Peng; Wang, Chao-Fu; Xin, Yu-Hu; Zhou, Lu; Li, Ying-Yi

2013-03-01

Pim-3 kinase has been shown to be aberrantly expressed in premalignant and malignant lesions of endoderm-derived organs such as the liver, pancreas, colon and stomach. Pim-3 kinase inactivates the Bad protein, a proapoptotic molecule, and improves the expression of Bcl-xL, an antiapoptotic molecule, to promote cell proliferation. Thus, blocking Pim-3 kinase activity may be a new strategy for the treatment of pancreatic cancer. In this study, we screened low molecular compounds and observed that the stemonamide synthetic intermediate, T-18, potently inhibited Pim kinase activity. Moreover, T-18 inhibited the proliferation of human pancreatic, as well as that of hepatocellular and colon cancer cells in vitro. It also induced the apoptosis of human pancreatic carcinoma cells in vitro by decreasing the levels of phospho-Ser112-Bad; the levels of Pim-3 kinase and total Bad protein were not altered. Furthermore, T-18 inhibited the growth of human pancreatic cancer cells in nude mice without apparent adverse effects when the tumor was palpable. These observations indicate that stemonamide synthetic intermediates may be novel drugs for the treatment of gastrointestinal cancers, particularly pancreatic cancer.

PIM-1 as a Solution-Processable “Molecular Basket” for CO 2 Capture from Dilute Sources

DOE PAGES

Pang, Simon H.; Jue, Melinda L.; Leisen, Johannes; ...

2015-12-07

Here, rising atmospheric CO 2 levels have triggered recent research into the science of amine materials supported on hard, porous materials such as mesoporous silica or alumina. While such materials can give high CO 2 uptakes and good sorption kinetics, they are difficult to utilize in practical applications due to difficulty in contacting large volumes of CO 2-laden gases with powder materials without significant pressure drops or sorbent attrition. Here, we describe a simple approach based on the impregnation of a permanently microporous polymer, PIM-1, with poly(ethylene imine) (PEI), removing the need for use of the hard oxide. PEI/PIM-1 compositesmore » demonstrate comparable performance to more traditionally studied oxide sorbents, with the benefit that PIM-1 is soluble in common solvents, making it eminently more viable for processing into morphologies that can facilitate heat and mass transfer and fabrication into low pressure drop contactors. In addition to adsorption studies performed on a variety of PEI/PIM-1 architectures, spin diffusion NMR studies were performed to suggest that PEI is well-dispersed within the PIM-1, allowing for rapid CO 2 adsorption.« less

[Effect of ginsenoside Rg3 on Pim-3 and Bad proteins in human pancreatic cancer cell line PANC-1].

PubMed

Jian, Jie; Hu, Zhi-Fang; Huang, Yuan

2009-05-01

Ginsenoside Rg3 is a traditional Chinese medicine monomer which possesses anticancer effects. This study was to investigate the effects of ginsenoside Rg3 on Pim-3 and phosphorylated Bad (pBad) proteins, pBad (Ser112) and pBad (Ser136) in human pancreatic cancer cell line PANC-1. PANC-1 cells were exposed to 10, 20, 40 and 80 micromol/L ginsenoside Rg3 for 24 h. A short hairpin RNA (shRNA) of Pim-3 was cloned and inserted into a eukaryotic expression vector pSilencer 3.1-H1 Neo to construct pSilencer 3.1-H1 Neo-Pim-3. pSilencer 3.1-H1 Neo-Pim-3 was then transfected into PANC-1 cells. Cell proliferation was measured by MTT assay; cell apoptosis was observed under an invert microscope and measured by flow cytometry with Annexin V/PI staining; protein expressions of Pim-3, Bad, pBad (Ser112) and pBad (Ser136) were measured by Western blot. The inhibitory rates of 10, 20, 40 and 80 micromol/L ginsenoside Rg3 on PANC-1 cells were 20.2%, 33.4%, 52.8% and 65.3%, respectively. Typical morphological changes in apoptosis were induced by ginsenoside Rg3. The apoptotic rate of PANC-1 cells was significantly higher in the ginsenoside Rg3 treatment group (80 micromol/L) than in the control group (12.2% vs. 3.3%, P<0.05). Ginsenoside Rg3 had no influence on the total Bad protein expression, but decreased both Pim-3 and pBad (Ser112) expressions in a dose-dependent manner. pBad (Ser136) was not expressed in PANC-1 cells. Compared with the control group, the percentages of early and total apoptotic cells were significantly increased in PANC-1 cells transfected with pim-3-shRNA [(11.5+/-3.7)% vs. (5.8+/-2.2)%,P<0.01;(20.8+/-2.6)% vs.(13.0+/-4.1)%,P<0.05], while the expressions of pim-3 and pBad (Ser112) were both decreased. The anti-tumor effect of ginsenoside Rg3 may be associated with the decrease of Pim-3 and pBad (Ser112).

Application of artificial neural networks to establish a predictive mortality risk model in children admitted to a paediatric intensive care unit.

PubMed

Chan, C H; Chan, E Y; Ng, D K; Chow, P Y; Kwok, K L

2006-11-01

Paediatric risk of mortality and paediatric index of mortality (PIM) are the commonly-used mortality prediction models (MPM) in children admitted to paediatric intensive care unit (PICU). The current study was undertaken to develop a better MPM using artificial neural network, a domain of artificial intelligence. The purpose of this retrospective case series was to compare an artificial neural network (ANN) model and PIM with the observed mortality in a cohort of patients admitted to a five-bed PICU in a Hong Kong non-teaching general hospital. The patients were under the age of 17 years and admitted to our PICU from April 2001 to December 2004. Data were collected from each patient admitted to our PICU. All data were randomly allocated to either the training or validation set. The data from the training set were used to construct a series of ANN models. The data from the validation set were used to validate the ANN and PIM models. The accuracy of ANN models and PIM was assessed by area under the receiver operator characteristics (ROC) curve and calibration. All data were randomly allocated to either the training (n=274) or validation set (n=273). Three ANN models were developed using the data from the training set, namely ANN8 (trained with variables required for PIM), ANN9 (trained with variables required for PIM and pre-ICU intubation) and ANN23 (trained with variables required for ANN9 and 14 principal ICU diagnoses). Three ANN models and PIM were used to predict mortality in the validation set. We found that PIM and ANN9 had a high ROC curve (PIM: 0.808, 95 percent confidence interval 0.552 to 1.000, ANN9: 0.957, 95 percent confidence interval 0.915 to 1.000), whereas ANN8 and ANN23 gave a suboptimal area under the ROC curve. ANN8 required only five variables for the calculation of risk, compared with eight for PIM. The current study demonstrated the process of predictive mortality risk model development using ANN. Further multicentre studies are required to produce a representative ANN-based mortality prediction model for use in different PICUs.

Inhibition of PIM1 kinase attenuates inflammation-induced pro-labour mediators in human foetal membranes in vitro.

PubMed

Lim, Ratana; Barker, Gillian; Lappas, Martha

2017-06-01

Does proviral integration site for Moloney murine leukaemic virus (PIM)1 kinase play a role in regulating the inflammatory processes of human labour and delivery? PIM1 kinase plays a critical role in foetal membranes in regulating pro-inflammatory and pro-labour mediators. Infection and inflammation have strong causal links to preterm delivery by stimulating pro-inflammatory cytokines and collagen degrading enzymes, which can lead to rupture of membranes. PIM1 has been shown to have a role in immune regulation and inflammation in non-gestational tissues; however, its role has not been explored in the field of human labour. PIM1 expression was analysed in myometrium and/or foetal membranes obtained at term and preterm (n = 8-9 patients per group). Foetal membranes, freshly isolated amnion cells and primary myometrial cells were used to investigate the effect of PIM1 inhibition on pro-labour mediators (n = 5 patients per treatment group). Foetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and from preterm pre-labour rupture of membranes (PPROM) (n = 9 per group). Amnion was collected from women with and without preterm chorioamnionitis (n = 8 per group). Expression of PIM1 kinase was determined by qRT-PCR and western blotting. To determine the effect of PIM1 kinase inhibition on the expression of pro-inflammatory and pro-labour mediators induced by bacterial products lipopolysaccharide (LPS) (10 μg/ml) and flagellin (1 μg/ml) and pro-inflammatory cytokine tumour necrosis factor (TNF) (10 ng/ml), chemical inhibitors SMI-4a (20 μM) and AZD1208 (50 μM) were used in foetal membrane explants and siRNA against PIM1 was used in primary amnion cells. Statistical significance was set at P < 0.05. PIM1 expression was significantly increased in foetal membranes after spontaneous term labour compared to no labour at term and in amnion with preterm chorioamnionitis compared to preterm with no chorioamnionitis. There was no change in PIM1 expression with preterm labour or PPROM compared to preterm with no labour or PPROM. In human foetal membranes, PIM1 inhibitors SMI-4a and AZD1208 significantly decreased the expression of pro-inflammatory cytokine interleukin-6 (IL6) and chemokines CXCL8 and CCL2 mRNA and release, prostaglandin prostaglandin F2α (PGF2α) release, adhesion molecule intercellular adhesion molecule 1 mRNA expression and release, and oxidative stress marker 8-isoprostane release after stimulation with either LPS or flagellin. Primary amnion cells transfected with PIM1 siRNA also showed decreased expression of IL6, CXCL8 and CCL2, PTGS2 mRNA and PGF2α release, and matrix metalloproteinase-9 (MMP9) expression, when stimulated with TNF. None. The conclusions were drawn from in vitro experiments using foetal membrane explants and primary cells isolated from amnion. Animal models are necessary to determine whether PIM1 kinase inhibitors can prevent spontaneous preterm birth in vivo. PIM1 kinase inhibitors may provide a novel therapeutic approach for preventing spontaneous preterm birth. Associate Professor Martha Lappas is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; grant no. 1047025). Funding for this study was provided by the NHMRC (grant no. 1058786), Norman Beischer Medical Research Foundation and the Mercy Research Foundation. The authors have no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Polypharmacy and potentially inappropriate medications: a cross-sectional analysis among 451 nursing homes in France.

PubMed

Herr, Marie; Grondin, Helene; Sanchez, Stéphane; Armaingaud, Didier; Blochet, Caroline; Vial, Antoine; Denormandie, Philippe; Ankri, Joël

2017-05-01

The quality of drug therapy is an important issue for nursing homes. This study aimed to assess the prevalence of polypharmacy and potentially inappropriate medications (PIMs) in a large sample of nursing home residents by using the data recorded during the preparation of pill dispensers. This is a cross-sectional study that included 451 nursing homes across France. Information about the medications received by the 30,702 residents (73.8% women) living in these nursing homes was extracted from the system that assists in the preparation of pill dispensers in pharmacies. The anonymized database included age, sex, and medications prescribed to residents, as well as nursing home characteristics (capacity, legal status). Factors associated with excessive polypharmacy (≥10 different drugs) and PIMs according to the Laroche list were studied using multilevel regression models. The average number of drugs prescribed was 6.9 ± 3.3, and excessive polypharmacy concerned 21.1% of the residents (n = 6468). According to the Laroche list, 47.4% of residents (n = 14,547) received at least one PIM. Benzodiazepines (excessive doses, long-acting benzodiazepines, and combination of benzodiazepines) and anticholinergic medications (hydroxyzine, cyamemazine, alimemazine) accounted for a large part of PIMs. Individual characteristics (age, gender) influenced the risk of receiving PIMs whereas nursing home characteristics (capacity, legal status) influenced the risk of excessive polypharmacy. This study shows that polypharmacy and PIMs remain highly prevalent among nursing home residents. Main PIMs concerned psychotropic and anticholinergic medications.

The putative oncogene Pim-1 in the mouse: its linkage and variation among t haplotypes.

PubMed

Nadeau, J H; Phillips, S J

1987-11-01

Pim-1, a putative oncogene involved in T-cell lymphomagenesis, was mapped between the pseudo-alpha globin gene Hba-4ps and the alpha-crystallin gene Crya-1 on mouse chromosome 17 and therefore within the t complex. Pim-1 restriction fragment variants were identified among t haplotypes. Analysis of restriction fragment sizes obtained with 12 endonucleases demonstrated that the Pim-1 genes in some t haplotypes were indistinguishable from the sizes for the Pim-1b allele in BALB/c inbred mice. There are now three genes, Pim-1, Crya-1 and H-2 I-E, that vary among independently derived t haplotypes and that have indistinguishable alleles in t haplotypes and inbred strains. These genes are closely linked within the distal inversion of the t complex. Because it is unlikely that these variants arose independently in t haplotypes and their wild-type homologues, we propose that an exchange of chromosomal segments, probably through double crossingover, was responsible for indistinguishable Pim-1 genes shared by certain t haplotypes and their wild-type homologues. There was, however, no apparent association between variant alleles of these three genes among t haplotypes as would be expected if a single exchange introduced these alleles into t haplotypes. If these variant alleles can be shown to be identical to the wild-type allele, then lack of association suggests that multiple exchanges have occurred during the evolution of the t complex.

Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer.

PubMed

Le, Xiuning; Antony, Rajee; Razavi, Pedram; Treacy, Daniel J; Luo, Flora; Ghandi, Mahmoud; Castel, Pau; Scaltriti, Maurizio; Baselga, Jose; Garraway, Levi A

2016-10-01

PIK3CA (which encodes the PI3K alpha isoform) is the most frequently mutated oncogene in breast cancer. Small-molecule PI3K inhibitors have shown promise in clinical trials; however, intrinsic and acquired resistance limits their utility. We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells. Among the validated resistance genes, Proviral Insertion site in Murine leukemia virus (PIM) kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. Concurrent pharmacologic inhibition of PIM and PI3K overcame this resistance mechanism. We also observed increased PIM expression and activity in a subset of breast cancer biopsies with clinical resistance to PI3K inhibitors. PIM1 overexpression was mutually exclusive with PIK3CA mutation in treatment-naïve breast cancers, suggesting downstream functional redundancy. Together, these results offer new insights into resistance to PI3K inhibitors and support clinical studies of combined PIM/PI3K inhibition in a subset of PIK3CA-mutant cancers. PIM kinase overexpression confers resistance to small-molecule PI3K inhibitors. Combined inhibition of PIM and PI3K may therefore be warranted in a subset of breast cancers. Cancer Discov; 6(10); 1134-47. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1069. ©2016 American Association for Cancer Research.

Exploring New Potentials of Blogs for Learning: Can Children Use Blogs for Personal Information Management (PIM)?

ERIC Educational Resources Information Center

Yeo, Hwan-Ik; Lee, Yekyung Lisa

2014-01-01

This study explores the use of blogs for personal information management (PIM) as a learning tool that could bring increased efficiency and academic self-efficacy for carrying out learning tasks. In order to identify the uses and effects of using blogs for PIM by children, a control group that used personal spaces within the class website and an…

Development of a computerized monitoring program to identify narcotic diversion in a pediatric anesthesia practice.

PubMed

Brenn, B Randall; Kim, Margaret A; Hilmas, Elora

2015-08-15

Development of an operational reporting dashboard designed to correlate data from multiple sources to help detect potential drug diversion by automated dispensing cabinet (ADC) users is described. A commercial business intelligence platform was used to create a dashboard tool for rapid detection of unusual patterns of ADC transactions by anesthesia service providers at a large pediatric hospital. By linking information from the hospital's pharmacy information management system (PIMS) and anesthesia information management system (AIMS) in an associative data model, the "narcotic reconciliation dashboard" can generate various reports to help spot outlier activity associated with ADC dispensing of controlled substances and documentation of medication waste processing. The dashboard's utility was evaluated by "back-testing" the program with historical data on an actual episode of diversion by an anesthesia provider that had not been detected through traditional methods of PIMS and AIMS data monitoring. Dashboard-generated reports on key metrics (e.g., ADC transaction counts, discrepancies in dispensed versus reconciled amounts of narcotics, PIMS-AIMS documentation mismatches) over various time frames during the period of known diversion clearly indicated the diverter's outlier status relative to other authorized ADC users. A dashboard program for correlating ADC transaction data with pharmacy and patient care data may be an effective tool for detecting patterns of ADC use that suggest drug diversion. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Are the argon metastables important in high power impulse magnetron sputtering discharges?

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

Gudmundsson, J. T., E-mail: tumi@hi.is; Science Institute, University of Iceland, Dunhaga 3, IS-107 Reykjavik; Lundin, D.

2015-11-15

We use an ionization region model to explore the ionization processes in the high power impulse magnetron sputtering (HiPIMS) discharge in argon with a titanium target. In conventional dc magnetron sputtering (dcMS), stepwise ionization can be an important route for ionization of the argon gas. However, in the HiPIMS discharge stepwise ionization is found to be negligible during the breakdown phase of the HiPIMS pulse and becomes significant (but never dominating) only later in the pulse. For the sputtered species, Penning ionization can be a significant ionization mechanism in the dcMS discharges, while in the HiPIMS discharge Penning ionization ismore » always negligible as compared to electron impact ionization. The main reasons for these differences are a higher plasma density in the HiPIMS discharge, and a higher electron temperature. Furthermore, we explore the ionization fraction and the ionized flux fraction of the sputtered vapor and compare with recent experimental work.« less

Hit to lead evaluation of 1,2,3-triazolo[4,5-b]pyridines as PIM kinase inhibitors.

PubMed

Pastor, Joaquín; Oyarzabal, Julen; Saluste, Gustavo; Alvarez, Rosa María; Rivero, Virginia; Ramos, Francisco; Cendón, Elena; Blanco-Aparicio, Carmen; Ajenjo, Nuria; Cebriá, Antonio; Albarrán, M I; Cebrián, David; Corrionero, Ana; Fominaya, Jesús; Montoya, Guillermo; Mazzorana, Marco

2012-02-15

PIM kinases have become targets of interest due to their association with biochemical mechanisms affecting survival, proliferation and cytokine production. 1,2,3-Triazolo[4,5-b]pyridines were identified as PIM inhibitors applying a scaffold hopping approach. Initial exploration around this scaffold and X-ray crystallographic data are hereby described. Copyright © 2012 Elsevier Ltd. All rights reserved.

PIM-1 kinase expression in adipocytic neoplasms: diagnostic and biological implications

PubMed Central

Nga, Min En; Swe, Nu Nu Ma; Chen, Kang Ting; Shen, Liang; Lilly, Michael B; Chan, Siew Pang; Salto-Tellez, Manuel; Das, Kakoli

2010-01-01

The differential diagnosis of soft tissue tumours poses a considerable challenge for pathologists, especially adipocytic tumours, as these may show considerable overlap in clinical presentation and morphological features with many other mesenchymal neoplasms. Hence, a specific and reliable marker that identifies adipocytic differentiation is much sought. We investigated the immunohistochemical expression of PIM-1 kinase in 35 samples of soft tissue tumours using tissue microarray technology and 49 full sections of adipocytic (n = 26) and non-adipocytic tumours (n = 23). Benign and malignant adipocytic tumours showed strong expression of PIM-1 while the non-adipocytic tumours were either negative or showed only weak staining for the protein. In myxoid liposarcomas, PIM-1 showed a distinct, unique vacuolar staining pattern, clearly outlining fine cytoplasmic lipid vacuoles. By contrast, non-adipocytic myxoid tumours (myxoma, chordoma and myxoid chondrosarcoma) did not show this vacuolar pattern of PIM-1 staining, although vacuolated cells were present on H&E. This differential expression was confirmed at a gene expression level in selected cases. Our results indicate that the expression of PIM-1 in adipose tissue may be a useful marker of adipocytic differentiation, in particular if the staining is both of high intensity and present in a unique, vacuolar pattern. PMID:19878356

Targeting PIM kinase enhances the activity of sunitinib in renal cell carcinoma.

PubMed

Mahalingam, D; Espitia, C M; Medina, E C; Esquivel, J A; Kelly, K R; Bearss, D; Choy, G; Taverna, P; Carew, J S; Giles, F J; Nawrocki, S T

2011-11-08

Upregulation of PIM kinase expression has been reported in many malignancies, suggesting that inhibition of PIM kinase activity may be an attractive therapeutic strategy. We hypothesised that inhibition of PIM kinase activity with SGI-1776, a novel small molecule inhibitor of PIM kinase activity, would reduce the viability of renal cell carcinoma (RCC) cells and enhance the activity of sunitinib. Immunoblotting, qRT-PCR, and gene expression arrays were carried out to identify genes modulated by SGI-1776 treatment. The anticancer activity of SGI-1776 and sunitinib was determined by viability and apoptosis assays and in tumour xenografts in vivo. Treatment with SGI-1776 led to a decrease in phosphorylated and total c-Myc levels, which resulted in the modulation of c-Myc target genes. SGI-1776 in combination with sunitinib induced a further reduction in c-Myc levels, which was associated with enhanced anticancer activity. siRNA-mediated knockdown of c-Myc demonstrated that its expression has a key role in regulating the sensitivity to the combination of SGI-1776 and sunitinib. Importantly, the combination significantly reduced tumour burden in two RCC xenograft models compared with single-agent therapy and was very well tolerated. These data indicate that targeting PIM kinase signalling is a promising treatment strategy for RCC. 2011 Cancer Research UK

Targeting PIM kinase enhances the activity of sunitinib in renal cell carcinoma

PubMed Central

Mahalingam, D; Espitia, C M; Medina, E C; Esquivel, J A; Kelly, K R; Bearss, D; Choy, G; Taverna, P; Carew, J S; Giles, F J; Nawrocki, S T

2011-01-01

Background: Upregulation of PIM kinase expression has been reported in many malignancies, suggesting that inhibition of PIM kinase activity may be an attractive therapeutic strategy. We hypothesised that inhibition of PIM kinase activity with SGI-1776, a novel small molecule inhibitor of PIM kinase activity, would reduce the viability of renal cell carcinoma (RCC) cells and enhance the activity of sunitinib. Methods: Immunoblotting, qRT–PCR, and gene expression arrays were carried out to identify genes modulated by SGI-1776 treatment. The anticancer activity of SGI-1776 and sunitinib was determined by viability and apoptosis assays and in tumour xenografts in vivo. Results: Treatment with SGI-1776 led to a decrease in phosphorylated and total c-Myc levels, which resulted in the modulation of c-Myc target genes. SGI-1776 in combination with sunitinib induced a further reduction in c-Myc levels, which was associated with enhanced anticancer activity. siRNA-mediated knockdown of c-Myc demonstrated that its expression has a key role in regulating the sensitivity to the combination of SGI-1776 and sunitinib. Importantly, the combination significantly reduced tumour burden in two RCC xenograft models compared with single-agent therapy and was very well tolerated. Conclusion: These data indicate that targeting PIM kinase signalling is a promising treatment strategy for RCC. PMID:22015557

Cytoplasmic Irradiation Induces Metabolic Shift in Human Small Airway Epithelial Cells via Activation of Pim-1 Kinase.

PubMed

Wu, Jinhua; Zhang, Qin; Wuu, Yen-Ruh; Zou, Sirui; Hei, Tom K

2017-04-01

The unique cellular and molecular consequences of cytoplasmic damage caused by ionizing radiation were studied using a precision microbeam irradiator. Our results indicated that targeted cytoplasmic irradiation induced metabolic shift from an oxidative to glycolytic phenotype in human small airway epithelial cells (SAE). At 24 h postirradiation, there was an increase in the mRNA expression level of key glycolytic enzymes as well as lactate secretion in SAE cells. Using RNA-sequencing analysis to compare genes that were responsive to cytoplasmic versus nuclear irradiation, we found a glycolysis related gene, Pim-1, was significantly upregulated only in cytoplasmic irradiated SAE cells. Inhibition of Pim-1 activity using the selective pharmaceutic inhibitor Smi-4a significantly reduced the level of lactate production and glucose uptake after cytoplasmic irradiation. In addition, Pim-1 also inhibited AMPK activity, which is a well-characterized negative regulator of glycolysis. Distinct from the glycolysis induced by cytoplasmic irradiation, targeted nuclear irradiation also induced a transient and minimal increase in glycolysis that correlated with increased expression of Hif-1α. In an effort to explore the underline mechanism, we found that inhibition of mitochondria fission using the cell-permeable inhibitor mdivi-1 suppressed the induction of Pim-1, thus confirming Pim-1 upregulation as a downstream effect of mitochondrial dysfunction. Our data show and, for the first time, that cytoplasmic irradiation mediate expression level of Pim-1, which lead to glycolytic shift in SAE cells. Additionally, since glycolysis is frequently linked to cancer cell metabolism, our findings further suggest a role of cytoplasmic damage in promoting neoplastic changes.

The Plasma Instrument for Magnetic Sounding (PIMS) on The Europa Clipper Mission

NASA Astrophysics Data System (ADS)

Westlake, Joseph H.; McNutt, Ralph L.; Kasper, Justin C.; Case, Anthony W.; Grey, Matthew P.; Kim, Cindy K.; Battista, Corina C.; Rymer, Abigail; Paty, Carol S.; Jia, Xianzhe; Stevens, Michael L.; Khurana, Krishan; Kivelson, Margaret G.; Slavin, James A.; Korth, Haje H.; Smith, Howard T.; Krupp, Norbert; Roussos, Elias; Saur, Joachim

2016-10-01

The Europa Clipper mission is equipped with a sophisticated suite of 9 instruments to study Europa's interior and ocean, geology, chemistry, and habitability from a Jupiter orbiting spacecraft. The Plasma Instrument for Magnetic Sounding (PIMS) on Europa Clipper is a Faraday Cup based plasma instrument whose heritage dates back to the Voyager spacecraft. PIMS will measure the plasma that populates Jupiter's magnetosphere and Europa's ionosphere. The science goals of PIMS are to: 1) estimate the ocean salinity and thickness by determining Europa's magnetic induction response, corrected for plasma contributions; 2) assess mechanisms responsible for weathering and releasing material from Europa's surface into the atmosphere and ionosphere; and 3) understand how Europa influences its local space environment and Jupiter's magnetosphere and vice versa.Europa is embedded in a complex Jovian magnetospheric plasma, which rotates with the tilted planetary field and interacts dynamically with Europa's ionosphere affecting the magnetic induction signal. Plasma from Io's temporally varying torus diffuses outward and mixes with the charged particles in Europa's own torus producing highly variable plasma conditions at Europa. PIMS works in conjunction with the Interior Characterization of Europa using Magnetometry (ICEMAG) investigation to probe Europa's subsurface ocean. This investigation exploits currents induced in Europa's interior by the moon's exposure to variable magnetic fields in the Jovian system to infer properties of Europa's subsurface ocean such as its depth, thickness, and conductivity. This technique was successfully applied to Galileo observations and demonstrated that Europa indeed has a subsurface ocean. While these Galileo observations contributed to the renewed interest in Europa, due to limitations in the observations the results raised major questions that remain unanswered. PIMS will greatly refine our understanding of Europa's global liquid ocean by accounting for contributions to the magnetic field from plasma currents.In this presentation we describe the principles of PIMS operations, detail the PIMS science goals, and discuss how to assess Europa's induction response.

The Plasma Instrument for Magnetic Sounding (PIMS) onboard the Europa Clipper Mission

NASA Astrophysics Data System (ADS)

Westlake, Joseph H.; McNutt, Ralph L.; Kasper, Justin C.; Rymer, Abigail; Case, Anthony; Battista, Corina; Cochrane, Corey; Coren, David; Crew, Alexander; Grey, Matthew; Jia, Xianzhe; Khurana, Krishan; Kim, Cindy; Kivelson, Margaret G.; Korth, Haje; Krupp, Norbert; Paty, Carol; Roussos, Elias; Stevens, Michael; Slavin, James A.; Smith, Howard T.; Saur, Joachim

2017-10-01

Europa is embedded in a complex Jovian magnetospheric plasma, which rotates with the tilted planetary field and interacts dynamically with Europa’s ionosphere affecting the magnetic induction signal. Plasma from Io’s temporally varying torus diffuses outward and mixes with the charged particles in Europa’s own torus producing highly variable plasma conditions. Onboard the Europa Clipper spacecraft the Plasma Instrument for Magnetic Sounding (PIMS) works in conjunction with the Interior Characterization of Europa using Magnetometry (ICEMAG) investigation to probe Europa’s subsurface ocean. This investigation exploits currents induced in Europa’s interior by the moon’s exposure to variable magnetic fields in the Jovian system to infer properties of Europa’s subsurface ocean such as its depth, thickness, and conductivity. This technique was successfully applied to Galileo observations and demonstrated that Europa indeed has a subsurface ocean. While these Galileo observations contributed to the renewed interest in Europa, due to limitations in the observations the results raised major questions that remain unanswered. PIMS will greatly refine our understanding of Europa’s global liquid ocean by accounting for contributions to the magnetic field from plasma currents.The Europa Clipper mission is equipped with a sophisticated suite of 9 instruments to study Europa's interior and ocean, geology, chemistry, and habitability from a Jupiter orbiting spacecraft. PIMS on Europa Clipper is a Faraday Cup based plasma instrument whose heritage dates back to the Voyager spacecraft. PIMS will measure the plasma that populates Jupiter’s magnetosphere and Europa’s ionosphere. The science goals of PIMS are to: 1) estimate the ocean salinity and thickness by determining Europa’s magnetic induction response, corrected for plasma contributions; 2) assess mechanisms responsible for weathering and releasing material from Europa’s surface into the atmosphere and ionosphere; and 3) understand how Europa influences its local space environment and Jupiter’s magnetosphere and vice versa.In this presentation we describe the principles of PIMS operations, detail the PIMS science goals, and discuss how to assess Europa's induction response.

The Plasma Instrument for Magnetic Sounding (PIMS) on The Europa Clipper Mission

NASA Astrophysics Data System (ADS)

Westlake, J. H.; McNutt, R. L., Jr.; Kasper, J. C.; Battista, C.; Case, A. W.; Cochrane, C.; Grey, M.; Jia, X.; Kivelson, M.; Kim, C.; Korth, H.; Khurana, K. K.; Krupp, N.; Paty, C. S.; Roussos, E.; Rymer, A. M.; Stevens, M. L.; Slavin, J. A.; Smith, H. T.; Saur, J.; Coren, D.

2017-12-01

The Europa Clipper mission is equipped with a sophisticated suite of 9 instruments to study Europa's interior and ocean, geology, chemistry, and habitability from a Jupiter orbiting spacecraft. The Plasma Instrument for Magnetic Sounding (PIMS) on Europa Clipper is a Faraday Cup based plasma instrument whose heritage dates back to the Voyager spacecraft. PIMS will measure the plasma that populates Jupiter's magnetosphere and Europa's ionosphere. The science goals of PIMS are to: 1) estimate the ocean salinity and thickness by determining Europa's magnetic induction response, corrected for plasma contributions; 2) assess mechanisms responsible for weathering and releasing material from Europa's surface into the atmosphere and ionosphere; and 3) understand how Europa influences its local space environment and Jupiter's magnetosphere and vice versa. Europa is embedded in a complex Jovian magnetospheric plasma, which rotates with the tilted planetary field and interacts dynamically with Europa's ionosphere affecting the magnetic induction signal. Plasma from Io's temporally varying torus diffuses outward and mixes with the charged particles in Europa's own torus producing highly variable plasma conditions at Europa. PIMS works in conjunction with the Interior Characterization of Europa using Magnetometry (ICEMAG) investigation to probe Europa's subsurface ocean. This investigation exploits currents induced in Europa's interior by the moon's exposure to variable magnetic fields in the Jovian system to infer properties of Europa's subsurface ocean such as its depth, thickness, and conductivity. This technique was successfully applied to Galileo observations and demonstrated that Europa indeed has a subsurface ocean. While these Galileo observations contributed to the renewed interest in Europa, due to limitations in the observations the results raised major questions that remain unanswered. PIMS will greatly refine our understanding of Europa's global liquid ocean by accounting for contributions to the magnetic field from plasma currents. In this presentation we describe the principles of PIMS operations, detail the PIMS science goals, and discuss how to assess Europa's induction response.

Inappropriate prescribing in a large community-dwelling older population: a focus on prevalence and how it relates to patient and physician characteristics.

PubMed

Amos, T B; Keith, S W; Del Canale, S; Orsi, P; Maggio, M; Baccarini, S; Gonzi, G; Liu, M; Maio, V

2015-02-01

The prescription of potentially inappropriate medications (PIMs) for older adults is a well-known population health concern. Updated country-specific estimates of inappropriate prescribing in older adults using germane explicit criteria are needed to facilitate physician-tailored quality improvement strategies. Therefore, we sought to determine the prevalence of PIMs for older adults in Emilia-Romagna, Italy, using the updated Maio criteria. We also evaluated patient and general practitioner (GP) characteristics related to inappropriate prescribing. Older adults (≥ 65) in 2012 were evaluated in a one-year retrospective study using administrative health care data. The 2011 Maio criteria includes 25 medications reimbursed by the Italian National Formulary, in the following categories in terms of severity: 16 medications that 'should always be avoided,' 3 that are 'rarely appropriate,' and 6 that have 'some indications although they are often misused.' To evaluate the extent of associations between patient and GP related characteristics, we used generalized estimating equations with an exchangeable covariance design to fit robust logistic regression models. A total of 865,354 older adults were in the cohort and 28% had at least one PIM. Of the entire cohort, 8%, 10%, and 14% of individuals were prescribed at least one medication that 'should always be avoided,' is 'rarely appropriate,' and has 'some indications but are often misused,' respectively. Older patients (≥ 75) and females were more likely to be exposed to PIMs. 2,923 GPs were identified in the region, each having prescribed at least one PIM, of which older GPs (≥ 56), male GPs, and solo practice GPs were more likely to prescribe PIMs to their older patients. The high prevalence of PIM exposure among older adults is a substantial issue in the region. Knowing how patient and GP characteristics relate to PIMs exposure may improve the design and targeting of initiatives for improving prescribing safety in this population. © 2014 John Wiley & Sons Ltd.

An operations-partnered evaluation of care redesign for high-risk patients in the Veterans Health Administration (VHA): Study protocol for the PACT Intensive Management (PIM) randomized quality improvement evaluation.

PubMed

Chang, Evelyn T; Zulman, Donna M; Asch, Steven M; Stockdale, Susan E; Yoon, Jean; Ong, Michael K; Lee, Martin; Simon, Alissa; Atkins, David; Schectman, Gordon; Kirsh, Susan R; Rubenstein, Lisa V

2018-06-01

Patient-centered medical homes have made great strides providing comprehensive care for patients with chronic conditions, but may not provide sufficient support for patients at highest risk for acute care use. To address this, the Veterans Health Administration (VHA) initiated a five-site demonstration project to evaluate the effectiveness of augmenting the VA's Patient Aligned Care Team (PACT) medical home with PACT Intensive Management (PIM) teams for Veterans at highest risk for hospitalization. Researchers partnered with VHA leadership to design a mixed-methods prospective multi-site evaluation that met leadership's desire for a rigorous evaluation conducted as quality improvement rather than research. We conducted a randomized QI evaluation and assigned high-risk patients to participate in PIM and compared them with high-risk Veterans receiving usual care through PACT. The summative evaluation examines whether PIM: 1) decreases VHA emergency department and hospital use; 2) increases satisfaction with VHA care; 3) decreases provider burnout; and 4) generates positive returns on investment. The formative evaluation aims to support improved care for high-risk patients at demonstration sites and to inform future initiatives for high-risk patients. The evaluation was reviewed by representatives from the VHA Office of Research and Development and the Office of Research Oversight and met criteria for quality improvement. VHA aims to function as a learning organization by rapidly implementing and rigorously testing QI innovations prior to final program or policy development. We observed challenges and opportunities in designing an evaluation consistent with QI standards and operations priorities, while also maintaining scientific rigor. This trial was retrospectively registered at ClinicalTrials.gov on April 3, 2017: NCT03100526. Protocol v1, FY14-17. Copyright © 2018 Elsevier Inc. All rights reserved.

Enhancing Adsorption Capacity while Maintaining Specific Recognition Performance of Mesoporous Silica: A Novel Imprinting Strategy with Amphiphilic Ionic Liquid as Surfactant.

PubMed

Ding, Shichao; Li, Zhiling; Cheng, Yuan; Du, Chunbao; Gao, Junfeng; Zhang, Yong-Wei; Zhang, Nan; Li, Zhaotong; Chang, Ninghui; Hu, Xiaoling

2018-06-21

In order to facilitate the broad applications of molecular recognition materials in biomedical areas, it is critical to enhance their adsorption capacity while maintaining their excellent recognition performance. In this work, we designed and synthesized well-defined peptide-imprinted mesoporous silica (PIMS) for specific recognition of an immunostimulating hexapeptide from human casein (IHHC) by using amphiphilic ionic liquid as the surfactant to anchor IHHC via a combination of one step sol-gel method and docking oriented imprinting approach. Thereinto, theoretical calculation was employed to reveal the multiple binding interactions and dual-template configuration between amphiphilic ionic liquid and IHHC. The fabricated PIMS was characterized and an in-depth analysis of specific recognition mechanism was conducted. Results revealed that both adsorption and recognition capabilities of PIMS far exceeded that of the NIMS's. More significantly, the PIMS exhibited a superior binding capacity (60.5 mg g-1), which could increase 18.9% than the previous work. The corresponding imprinting factor and selectivity coefficient could reach up to 4.51 and 3.30, respectively. The PIMS also possessed lickety-split kinetic binding for IHHC, which the equilibrium time was only 10 min. All of these merits were due to the high surface area and the synergistic effect of multiple interactions (including hydrogen bonding, π-π stacking, ion-ion electrostatic interactions and van der Waals interactions, etc.) between PIMS and IHHC in imprinted sites. The present work suggests the potential application of PIMS for large-scale and high-effective separation of IHHC, which may lead to their broad applications in drug/gene deliver, biosensors, catalyst and so on. © 2018 IOP Publishing Ltd.

Experiments on PIM in Support of the Development of IVA Technology for Radiography at AWE

NASA Astrophysics Data System (ADS)

Clough, Stephen G.; Thomas, Kenneth J.; Williamson, Mark C.; Phillips, Martin J.; Smith, Ian D.; Bailey, Vernon L.; Kishi, Hiroshi J.; Maenchen, John E.; Johnson, David L.

2002-12-01

The PIM machine has been designed and constructed at AWE as part of a program to investigate IVA technology for radiographic applications. PIM, as originally constructed, was a prospective single module of a 14 MV, 100 kA, ten module machine. The design of such a machine is a primary goal of the program as several are required to provide multi-axis radiography in a new Hydrodynamics Research Facility (HRF). Another goal is to design lower voltage machines (ranging from 1 to 5 MV) utilizing PIM style components. The original PIM machine consisted of a single inductive cavity pulsed by a 10 ohm water dielectric Blumlein pulse forming line (PFL) charged by a Marx generator. These components successfully achieved their design voltages and data on the prepulse was obtained showing it to be worse than expected. This information provided a basis for design work on the 14 MV HRF IVA, carried out by Titan-PSD, resulting in a proposal for a prepulse switch, a prototype of which should be installed on PIM by the end of this year. The original single, coaxial switch used to initiate the Blumlein has been replaced by a prototype laser triggered switching arrangement, also designed by Titan-PSD, which it was desired to test prior to its eventual use in the HRF. Despite problems with the laser, which will necessitate further experiments, it was determined that laser triggering with low jitter was occurring. A split oil co-ax feed has now been used to install a second cavity, in parallel with the first, on the PIM Blumlein. This two cavity configuration provides a prototype for future radiographic machines operating at up to 3 MV and a test facility for diode research.

Low-molecular-weight carbohydrate Pentaisomaltose may replace dimethyl sulfoxide as a safer cryoprotectant for cryopreservation of peripheral blood stem cells.

PubMed

Svalgaard, Jesper Dyrendom; Haastrup, Eva Kannik; Reckzeh, Kristian; Holst, Bjørn; Glovinski, Peter Viktor; Gørløv, Jette Sønderskov; Hansen, Morten Bagge; Moench, Kim Theilgaard; Clausen, Christian; Fischer-Nielsen, Anne

2016-05-01

Cryopreserved hematopoietic stem cell products are widely used for certain hematologic malignancies. Dimethyl sulfoxide (DMSO) is the most widely used cryoprotective agent (CPA) today, but due to indications of cellular toxicity, changes of the cellular epigenetic state, and patient-related side effects, there is an increasing demand for DMSO-free alternatives. We therefore investigated whether Pentaisomaltose (PIM), a low-molecular-weight carbohydrate (1 kDa), can be used for cryopreservation of peripheral blood stem cells, more specifically hematopoietic progenitor cell apheresis (HPC(A)) product. We cryopreserved patient or donor HPC(A) products using 10% DMSO or 16% PIM and quantified the recovery of CD34+ cells and CD34+ subpopulations by multicolor flow cytometry. In addition, we compared the frequency of HPCs after DMSO and PIM cryopreservation using the colony-forming cells (CFCs) assay. The mean CD34+ cell recovery was 56.3 ± 23.7% (11.4%-97.3%) and 58.2 ± 10.0% (45.7%-76.9%) for 10% DMSO and 16% PIM, respectively. The distribution of CD34+ cell subpopulations was similar when comparing DMSO or PIM as CPA. CFC assay showed mean colony numbers of 70.7 ± 25.4 (range, 37.8-115.5) and 67.7 ± 15.7 (range, 48-86) for 10% DMSO and 16% PIM, respectively. Our findings demonstrate that PIM cryopreservation of HPC(A) products provides recovery of CD34+ cells, CD34+ subpopulations, and CFCs similar to that of DMSO cryopreservation and therefore may have the potential to be used for cryopreservation of peripheral blood stem cells. © 2016 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells.

PubMed

Lee, Miso; Lee, Kyung-Hun; Min, Ahrum; Kim, Jeongeun; Kim, Seongyeong; Jang, Hyemin; Lim, Jee Min; Kim, So Hyeon; Ha, Dong-Hyeon; Jeong, Won Jae; Suh, Koung Jin; Yang, Yae-Won; Kim, Tae Yong; Oh, Do-Youn; Bang, Yung-Jue; Im, Seock-Ah

2018-06-06

Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.

Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).

PubMed

Ark, B; Gummere, G; Bennett, D; Artzt, K

1991-06-01

Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytoplasmic Irradiation Induces Metabolic Shift in Human Small Airway Epithelial Cells via Activation of Pim-1 Kinase

PubMed Central

Wu, Jinhua; Zhang, Qin; Wuu, Yen-Ruh; Zou, Sirui; Hei, Tom K.

2017-01-01

The unique cellular and molecular consequences of cytoplasmic damage caused by ionizing radiation were studied using a precision microbeam irradiator. Our results indicated that targeted cytoplasmic irradiation induced metabolic shift from an oxidative to glycolytic phenotype in human small airway epithelial cells (SAE). At 24 h postirradiation, there was an increase in the mRNA expression level of key glycolytic enzymes as well as lactate secretion in SAE cells. Using RNA-sequencing analysis to compare genes that were responsive to cytoplasmic versus nuclear irradiation, we found a glycolysis related gene, Pim-1, was significantly upregulated only in cytoplasmic irradiated SAE cells. Inhibition of Pim-1 activity using the selective pharmaceutic inhibitor Smi-4a significantly reduced the level of lactate production and glucose uptake after cytoplasmic irradiation. In addition, Pim-1 also inhibited AMPK activity, which is a well-characterized negative regulator of glycolysis. Distinct from the glycolysis induced by cytoplasmic irradiation, targeted nuclear irradiation also induced a transient and minimal increase in glycolysis that correlated with increased expression of Hif-1α. In an effort to explore the underline mechanism, we found that inhibition of mitochondria fission using the cell-permeable inhibitor mdivi-1 suppressed the induction of Pim-1, thus confirming Pim-1 upregulation as a downstream effect of mitochondrial dysfunction. Our data show and, for the first time, that cytoplasmic irradiation mediate expression level of Pim-1, which lead to glycolytic shift in SAE cells. Additionally, since glycolysis is frequently linked to cancer cell metabolism, our findings further suggest a role of cytoplasmic damage in promoting neoplastic changes. PMID:28170315

SGI-1776, an imidazo pyridazine compound, inhibits the proliferation of ovarian cancer cells by inactivating Pim-1.

PubMed

Xie, Jing; Bai, Jun

2014-07-01

To investigate the antitumor effect of SGI-1776 on human ovarian cancer HO-8910 cells and its molecular mechanism. HO-8910 cells were cultured in vitro, and the proliferation inhibitory effects of SGI- 1776 were determined by MTT assay and colony formation assay. The effect of SGI-1776 on the distribution of cell cycle phase was observed by flow cytometry with propidium iodide (PI) staining. The inhibition rate of migration and invasion were valued by transwell cell assay. Multiple molecular techniques, such as ELISA, Western blot, siRNA and cDNA transfection were used to explore the molecular mechanism. SGI-1776 presented dramatic anti-tumor activity against HO-8910 cells in vitro, inhibited the cells proliferation and colony formation, and attenuated the migration and invasion in a dosedependent manner, accompanied by cell cycle arrest in G1 phase. SGI-1776 caused the proliferation inhibition with concomitant decrease in Pim-1 kinase activity, down-regulated the expression of Pim-1 protein and and its downstream genes, such as CDK6, pCDK6, CDK4, pCDK4, CDK2 and pCDK2, and increased the expression of P21 and P27. Down-regulation expression of Pim-1 by siRNA followed SGI-1776 treatment resulted in enhanced cell proliferation inhibition rate and attenuated migration/invasion. Up-regulation of Pim-1 by cDNA transfection attenuated SGI- 1776-induced cell proliferation inhibition and its migration/invasion. Pim-1 mediates the biological effect of SGI-1776 in human ovarian cancer HO-8910 cells, suggesting Pim-1 might be a novel target for human ovarian cancer.

[Prevalence of potentially inappropriate drug prescription in the elderly].

PubMed

Fajreldines, A; Insua, J; Schnitzler, E

2016-01-01

One of the causes of preventable adverse drug events (ADES) in older patients constitutes inappropriate prescription of drugs (PIM). The PIM is where risks exceed the clinical benefit. Several instruments can be use to measure this problem, the most used are: a) Beers criteria; b) Screening tool to Older People Potentially inappropriate Prescription (STOPP); c) Screening tool to Alert Doctors to Right Appropriate indicated Treatments (START); d) The Medication Appropriateness Index (MAI). This study aims to assess the prevalence of PIM, in a population of older adults in three clinical scopes of university hospital. cross sectional study of 300 cases from a random sample of fields: hospitalization (n=100), ambulatory (n=100) and emergency (n=100), all patients over 65 years old or more who where treated at our hospital. 1355 prescription drugs were analized, finding patients hospitalized (PIM) of 57.7%, 55%, 26%, and 80% according to Beers, in ambulatory 36%, 36.5%, 5% and 52% with the same tools and in emergency 35%, 35%, 6% y 52% with the same tools. Was found significant association the PIM with polipharmacy with Beers, STOPP and MAI. results can be compare to world literature (26-80% vs 11-73.1%). The STOPP-START used in an integrated manner would be best estimating the problem of PIM. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

Risk factors for the prescription of potentially inappropriate medication (PIM) in the elderly : an analysis of sickness fund routine claims data from Germany.

PubMed

Stock, Stephanie; Redaelli, Marcus; Simic, Dusan; Siegel, Martin; Henschel, Frank

2014-10-01

Elderly people are especially prone to suffer adverse drug reactions (ADR). Main reasons for the higher vulnerability of the elderly to ADR are changes in metabolism as i.e. slower renal clearance and polypharmacie which often results from multimorbidity. To prevent ADR careful prescription with special consideration of these aspects is warranted. To help physicians avoid drugs which are especially likely to cause ADR lists have been developed following the consensus method process. For Germany this list is called the PRISCUS list. It was developed based on a literature review, review of international lists such as the American Beers list, and a consensus process based on a Delphi survey. It contains 83 drugs from 18 classes which are classified as potentially inapropriate medication (PIM). It also lists alternatives for each PIM. If a drug is registered with the PRISCUS list this does not mean automatically that it is contraindicated in the elderly but that special caution should be excercised in prescribing the drug, alternatives should be considered and the patient carefully monitored.Prescription rates for PIMs in Germany in the elderly is pretty much stable at around 23% with only a small decline in the past years. Also, more than 5% of all prescriptions in the elderly are PIM prescriptions. Physicians specially trained in geriatrics tend to prescribe less PIMs compared to other physicians.

A potential therapeutic target for FLT3-ITD AML: PIM1 Kinase

PubMed Central

Fathi, Amir T.; Arowojolu, Omotayo; Swinnen, Ian; Sato, Takashi; Rajkhowa, Trivikram; Small, Donald; Marmsater, Fredrik; Robinson, John E.; Gross, Stefan David; Martinson, Matthew; Allen, Shelley; Kallan, Nicholas C.; Levis, Mark

2011-01-01

Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) mutation have a poor prognosis, and FLT3 inhibitors are now under clinical investigation. PIM1, a serine/threonine kinase, is up-regulated in FLT3-ITD AML and may be involved in FLT3-mediated leukemogenesis. We employed a PIM1 inhibitor, AR00459339 (Array Biopharma Inc.), to investigate the effect of PIM1 inhibition in FLT3-mutant AML. Like FLT3 inhibitors, AR00459339 was preferentially cytotoxic to FLT3-ITD cells, as demonstrated in the MV4-11, Molm-14, and TF/ITD cell lines, as well as 12 FLT3-ITD primary samples. Unlike FLT3 inhibitors, AR00459339 did not suppress phosphorylation of FLT3, but did promote the de-phosphorylation of downstream FLT3 targets, STAT5, AKT, and BAD. Combining AR00459339 with a FLT3 inhibitor resulted in additive to mildly synergistic cytotoxic effects. AR00459339 was cytotoxic to FLT3-ITD samples from patients with secondary resistance to FLT3 inhibitors, suggesting a novel benefit to combining these agents. We conclude that PIM1 appears to be closely associated with FLT3 signaling, and that inhibition of PIM1 may hold therapeutic promise, either as monotherapy, or by overcoming resistance to FLT3 inhibitors. PMID:21802138

The influence of impression management scales on the Personality Assessment Inventory in the epilepsy monitoring unit.

PubMed

Purdom, Catherine L; Kirlin, Kristin A; Hoerth, Matthew T; Noe, Katherine H; Drazkowski, Joseph F; Sirven, Joseph I; Locke, Dona E C

2012-12-01

The Somatic Complaints scale (SOM) and Conversion subscale (SOM-C) of the Personality Assessment Inventory perform best in classifying psychogenic non-epileptic seizures (PNES) from epileptic seizures (ES); however, the impact of positive impression management (PIM) and negative impression management (NIM) scales on SOM and SOM-C classification has not been examined. We studied 187 patients from an epilepsy monitoring unit with confirmed PNES or ES. On SOM, the best cut score was 72.5 T when PIM was elevated and 69.5 T when there was no bias. On SOM-C, when PIM was elevated, the best cut score was 67.5 T and 76.5 T when there was no bias. Negative impression management elevations (n=9) were too infrequent to analyze separately. Despite similarities in classification accuracy, there were differences in sensitivity and specificity with and without PIM, impacting positive and negative predictive values. The presence of PIM bias generally increases positive predictive power of SOM and SOM-C but decreases negative predictive power. Copyright © 2012 Elsevier Inc. All rights reserved.

Systematic functional characterization of resistance to PI3K inhibition in breast cancer

PubMed Central

Treacy, Daniel J.; Luo, Flora; Ghandi, Mahmoud; Castel, Pau; Scaltriti, Maurizio; Baselga, Jose; Garraway, Levi A.

2016-01-01

PIK3CA (which encodes the phosphoinositide-3 kinase (PI3K) alpha isoform) is the most frequently mutated oncogene in breast cancer. Small-molecule PI3K inhibitors have shown promise in clinical trials; however, intrinsic and acquired resistance limits their utility. We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells. Among the validated resistance genes, PIM kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. Concurrent pharmacological inhibition of PIM and PI3K overcame this resistance mechanism. We also observed upregulated PIM expression and activity in a subset of breast cancer biopsies with clinical resistance to PI3K inhibitors. PIM1 overexpression is mutually exclusive with PIK3CA mutation in treatment-naïve breast cancers, suggesting downstream functional redundancy. Together, these results offer new insights into resistance to PI3K inhibitors and support clinical studies of combined PIM/PI3K inhibition in a subset of PIK3CA-mutant cancers. PMID:27604488

One Year Report for SAMS and OARE on STS-73/USML-2. Experiment 36

NASA Technical Reports Server (NTRS)

Hakimzadeh, Roshanak

1998-01-01

The Second United States Microgravity Laboratory (USML-2) payload flew on the orbiter Columbia on mission STS-73 from October 20 to November 5, 1995. The USML-2 payload on STS-73 was dedicated to microgravity experiments. Two accelerometer systems managed by the NASA Lewis Research Center (LeRC) flew to support these experiments, namely the Orbital Acceleration Research Experiment (OARE) and the Space Acceleration Measurements System (SAMS). OARE downlinked real-time quasi-steady acceleration data, which were provided to the investigators. The SAMS recorded higher frequency data onboard for post-mission analysis. The Principal Investigator Microgravity Services (PIMS) project at NASA LeRC supports principal investigators of microgravity experiments as they evaluate the effects of varying acceleration levels on their experiments. A summary report was prepared by PIMS to furnish interested experiment investigators with a guide to evaluate the acceleration environment during STS-73, and as a means of identifying areas which require further study. The summary report provides an overview of the STS-73 mission, describes the accelerometer systems flown on this mission, discusses some specific analyses of the accelerometer data in relation to the various activities which occurred during the mission, and presents plots resulting from these analyses as a snapshot of the environment during the mission. Numerous activities occurred during the STS-73 mission that are of interest to the low-gravity community. Specific activities of interest during this mission were crew exercise, payload bay door motion, Glovebox fan operations, water dumps, Ku band antenna activity, orbital maneuvering system, and primary reaction control system firings, and attitude changes. The low-gravity environment related to these activities is discussed in the summary report.

Ultrathin Composite Polymeric Membranes for CO2 /N2 Separation with Minimum Thickness and High CO2 Permeance.

PubMed

Benito, Javier; Sánchez-Laínez, Javier; Zornoza, Beatriz; Martín, Santiago; Carta, Mariolino; Malpass-Evans, Richard; Téllez, Carlos; McKeown, Neil B; Coronas, Joaquín; Gascón, Ignacio

2017-10-23

The use of ultrathin films as selective layers in composite membranes offers significant advantages in gas separation for increasing productivity while reducing the membrane size and energy costs. In this contribution, composite membranes have been obtained by the successive deposition of approximately 1 nm thick monolayers of a polymer of intrinsic microporosity (PIM) on top of dense membranes of the ultra-permeable poly[1-(trimethylsilyl)-1-propyne] (PTMSP). The ultrathin PIM films (30 nm in thickness) demonstrate CO 2 permeance up to seven times higher than dense PIM membranes using only 0.04 % of the mass of PIM without a significant decrease in CO 2 /N 2 selectivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Therapeutic Value of PLK1 Knockdown in Combination with Prostate Cancer Drugs in PIM-1 Overexpressing Prostate Cancer Cells

DTIC Science & Technology

2014-11-13

PIM kinases are not required for essential cellular functions . Furthermore, the presence of a unique hinge region in the ATP-binding site of PIM1...washing and blocking, cells were incubated with the appropriate primary antibodies overnight and incubated with fluorescent secondary antibodies...determined after 72 hrs of reverse transfection by using the CellTiter-Glo Luminescent cell viability assay and the results were normalized to RISC -free siRNA

Pim-1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

DTIC Science & Technology

2007-10-01

submitted to the Journal of Biological Chemistry . BODY We will outline our progress through reference to the specific aims described above. The first... Chemistry (see manuscript in appendix). The goal of specific aim #2 was to define pathways through which the PIM1 kinase could activate NFkB...or with three other flavonoids , has been determined. We have also shown that quercetagetin is able to inhibit the activity of the PIM1 kinase in

A passive integrative sampler for mercury vapor in air and neutral mercury species in water

USGS Publications Warehouse

Brumbaugh, W.G.; Petty, J.D.; May, T.W.; Huckins, J.N.

2000-01-01

A passive integrative mercury sampler (PIMS) based on a sealed polymeric membrane was effective for the collection and preconcentration of Hg0. Because the Hg is both oxidized and stabilized in the PIMS, sampling intervals of weeks to months are possible. The effective air sampling rate for a 15 x 2.5 cm device was about 21-equivalents/day (0.002 m3/day) and the detection limit for 4-week sampling was about 2 ng/m3 for conventional ICP-MS determination without clean-room preparation. Sampling precision was ??? 5% RSD for laboratory exposures, and 5-10% RSD for field exposures. These results suggest that the PIMS could be useful for screening assessments of Hg contamination and exposure in the environment, the laboratory, and the workplace. The PIMS approach may be particularly useful for applications requiring unattended sampling for extended periods at remote locations. Preliminary results indicate that sampling for dissolved gaseous mercury (DGM) and potentially other neutral mercury species from water is also feasible. Rigorous validation of the sampler performance is currently in progress. (C) 1999 Elsevier Science Ltd.A passive integrative mercury sampler (PIMS) based on a sealed polymeric membrane was effective for the collection and preconcentration of Hg0. Because the Hg is both oxidized and stabilized in the PIMS, sampling intervals of weeks to months are possible. The effective air sampling rate for a 15??2.5 cm device was about 21-equivalents/day (0.002 m3/day) and the detection limit for 4-week sampling was about 2 ng/m3 for conventional ICP-MS determination without clean-room preparation. Sampling precision was ???5% RSD for laboratory exposures, and 5-10% RSD for field exposures. These results suggest that the PIMS could be useful for screening assessments of Hg contamination and exposure in the environment, the laboratory, and the workplace. The PIMS approach may be particularly useful for applications requiring unattended sampling for extended periods at remote locations. Preliminary results indicate that sampling for dissolved gaseous mercury (DGM) and potentially other neutral mercury species from water is also feasible. Rigorous validation of the sampler performance is currently in progress.

Cell and gene therapy for severe heart failure patients: The time and place for Pim-1 Kinase

PubMed Central

Siddiqi, Sailay; Sussman, Mark A

2014-01-01

Regenerative therapy in severe heart failure patients presents a challenging set of circumstances including a damaged myocardial environment that accelerates senescence in myocytes and cardiac progenitor cells. Failing myocardium suffers from deterioration of contractile function coupled with impaired regenerative potential that drives the heart toward decompensation. Efficacious regenerative cell therapy for severe heart failure requires disruption of this vicious circle that can be accomplished by alteration of the compromised myocyte phenotype and rejuvenation of progenitor cells. This review focuses upon potential for Pim-1 kinase to mitigate chronic heart failure by improving myocyte quality through preservation of mitochondrial integrity, prevention of hypertrophy and inhibition of apoptosis. In addition, cardiac progenitors engineered with Pim-1 possess enhanced regenerative potential, making Pim-1 an important player in future treatment of severe heart failure. PMID:23984924

Highly ionized physical vapor deposition plasma source working at very low pressure

NASA Astrophysics Data System (ADS)

Stranak, V.; Herrendorf, A.-P.; Drache, S.; Cada, M.; Hubicka, Z.; Tichy, M.; Hippler, R.

2012-04-01

Highly ionized discharge for physical vapor deposition at very low pressure is presented in the paper. The discharge is generated by electron cyclotron wave resonance (ECWR) which assists with ignition of high power impulse magnetron sputtering (HiPIMS) discharge. The magnetron gun (with Ti target) was built into the single-turn coil RF electrode of the ECWR facility. ECWR assistance provides pre-ionization effect which allows significant reduction of pressure during HiPIMS operation down to p = 0.05 Pa; this is nearly more than an order of magnitude lower than at typical pressure ranges of HiPIMS discharges. We can confirm that nearly all sputtered particles are ionized (only Ti+ and Ti++ peaks are observed in the mass scan spectra). This corresponds well with high plasma density ne ˜ 1018 m-3, measured during the HiPIMS pulse.

Pim kinase inhibition sensitizes FLT3-ITD acute myeloid leukemia cells to topoisomerase 2 inhibitors through increased DNA damage and oxidative stress

PubMed Central

Doshi, Kshama A.; Trotta, Rossana; Natarajan, Karthika; Rassool, Feyruz V.; Tron, Adriana E.; Huszar, Dennis; Perrotti, Danilo; Baer, Maria R.

2016-01-01

Internal tandem duplication of fms-like tyrosine kinase-3 (FLT3-ITD) is frequent (30 percent) in acute myeloid leukemia (AML), and is associated with short disease-free survival following chemotherapy. The serine threonine kinase Pim-1 is a pro-survival oncogene transcriptionally upregulated by FLT3-ITD that also promotes its signaling in a positive feedback loop. Thus inhibiting Pim-1 represents an attractive approach in targeting FLT3-ITD cells. Indeed, co-treatment with the pan-Pim kinase inhibitor AZD1208 or expression of a kinase-dead Pim-1 mutant sensitized FLT3-ITD cell lines to apoptosis triggered by chemotherapy drugs including the topoisomerase 2 inhibitors daunorubicin, etoposide and mitoxantrone, but not the nucleoside analog cytarabine. AZD1208 sensitized primary AML cells with FLT3-ITD to topoisomerase 2 inhibitors, but did not sensitize AML cells with wild-type FLT3 or remission bone marrow cells, supporting a favorable therapeutic index. Mechanistically, the enhanced apoptosis observed with AZD1208 and topoisomerase 2 inhibitor combination treatment was associated with increased DNA double-strand breaks and increased levels of reactive oxygen species (ROS), and co-treatment with the ROS scavenger N-acetyl cysteine rescued FLT3-ITD cells from AZD1208 sensitization to topoisomerase 2 inhibitors. Our data support testing of Pim kinase inhibitors with topoisomerase 2 inhibitors, but not with cytarabine, to improve treatment outcomes in AML with FLT3-ITD. PMID:27374090

The DE-PHARM Project: A Pharmacist-Driven Deprescribing Initiative in a Nursing Facility.

PubMed

Pruskowski, Jennifer; Handler, Steven M

2017-08-01

Many residents with life-limiting illnesses are being prescribed and taking potentially inappropriate medications (PIMs) and questionably beneficial medications either near or at the end of life. These medications can contribute to adverse drug reactions, increase morbidity, and increase unnecessary burden and cost. It is crucial that the process of deprescribing be incorporated into the care of these residents. After developing a clinical pharmacist-driven deprescribing initiative in the nursing facility, the objective of this project was to reduce the number of PIMs via accepted recommendations from the clinical pharmacist to the primary team. The Discussion to Ensure the Patient-centered, Health-focused, prognosis-Appropriate, and Rational Medication regimen (DE-PHARM) quality improvement-approved project was conducted in an urban, academic nursing facility in Pittsburgh, Pennsylvania. The pilot phase occurred between October 2015 and April 2016. To be included in this study, participants had to be a custodial resident of the nursing facility with a previously documented comfort-focused treatment plan. All medications used for the management of chronic comorbid diseases were eligible for review. Forty-seven residents managed by eight different primary teams met inclusion criteria. Thirty-nine recommendations for 23 residents were made by the clinical pharmacist, with an average of 0.82 and range of 0-5 recommendations per resident, respectively. Of those, only 10 (26%) were accepted, 1 (3%) was modified, 3 (7%) were rejected, and 25 (64%) had no response within the 120-day response period. Additionally, two residents died during the project, and one resident was readmitted to the hospital for a prolonged period of time. The pilot phase of the DE-PHARM project, a clinical pharmacist-driven deprescribing initiative, was designed and assessed. This project demonstrated the feasibility of such an initiative. Because of the complexity of such a process, special attention must be paid to eligible residents and medications, the need for interprofessional collaboration, and the operational process. This project is ongoing in other nursing facilities in Western Pennsylvania.

Nonbinary quantification technique accounting for myocardial infarct heterogeneity: Feasibility of applying percent infarct mapping in patients.

PubMed

Mastrodicasa, Domenico; Elgavish, Gabriel A; Schoepf, U Joseph; Suranyi, Pal; van Assen, Marly; Albrecht, Moritz H; De Cecco, Carlo N; van der Geest, Rob J; Hardy, Rayphael; Mantini, Cesare; Griffith, L Parkwood; Ruzsics, Balazs; Varga-Szemes, Akos

2018-02-15

Binary threshold-based quantification techniques ignore myocardial infarct (MI) heterogeneity, yielding substantial misquantification of MI. To assess the technical feasibility of MI quantification using percent infarct mapping (PIM), a prototype nonbinary algorithm, in patients with suspected MI. Prospective cohort POPULATION: Patients (n = 171) with suspected MI referred for cardiac MRI. Inversion recovery balanced steady-state free-precession for late gadolinium enhancement (LGE) and modified Look-Locker inversion recovery (MOLLI) T 1 -mapping on a 1.5T system. Infarct volume (IV) and infarct fraction (IF) were quantified by two observers based on manual delineation, binary approaches (2-5 standard deviations [SD] and full-width at half-maximum [FWHM] thresholds) in LGE images, and by applying the PIM algorithm in T 1 and LGE images (PIM T1 ; PIM LGE ). IV and IF were analyzed using repeated measures analysis of variance (ANOVA). Agreement between the approaches was determined with Bland-Altman analysis. Interobserver agreement was assessed by intraclass correlation coefficient (ICC) analysis. MI was observed in 89 (54.9%) patients, and 185 (38%) short-axis slices. IF with 2, 3, 4, 5SDs and FWHM techniques were 15.7 ± 6.6, 13.4 ± 5.6, 11.6 ± 5.0, 10.8 ± 5.2, and 10.0 ± 5.2%, respectively. The 5SD and FWHM techniques had the best agreement with manual IF (9.9 ± 4.8%) determination (bias 1.0 and 0.2%; P = 0.1426 and P = 0.8094, respectively). The 2SD and 3SD algorithms significantly overestimated manual IF (9.9 ± 4.8%; both P < 0.0001). PIM LGE measured significantly lower IF (7.8 ± 3.7%) compared to manual values (P < 0.0001). PIM LGE , however, showed the best agreement with the PIM T1 reference (7.6 ± 3.6%, P = 0.3156). Interobserver agreement was rated good to excellent for IV (ICCs between 0.727-0.820) and fair to good for IF (0.589-0.736). The application of the PIM LGE technique for MI quantification in patients is feasible. PIM LGE , with its ability to account for voxelwise MI content, provides significantly smaller IF than any thresholding technique and shows excellent agreement with the T 1 -based reference. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Hierarchical porous membrane via electrospinning PIM-1 for micropollutants removal

NASA Astrophysics Data System (ADS)

Pan, Ying; Zhang, Lijie; Li, Zhaojing; Ma, Liujia; Zhang, Yufeng; Wang, Jun; Meng, Jianqiang

2018-06-01

Ideal adsorbents are featured by both high adsorption capacity and high adsorption rate. Current adsorptive membranes enjoy good mass transfer performance but have limited sorption capacity. Microporous organic polymer has superiorities of small pore size and high surface area which is conductive to high adsorption capacity, but usually suffers from high mass transfer resistance. In this work, the polymer of intrinsic microporosity PIM-1 was fabricated into microfiber membranes by electrospinning for carbendazim and phenol adsorption. The PIM-1 and its electrospun membranes were characterized by 1H NMR, GPC, ATR-FTIR, FESEM, TG and BET measurements. The electrospun PIM-1 membrane was demonstrated to have hierarchical porous structure with high surface area. The equilibrium adsorption capacity for carbendazim and phenol was 0.084 mmol/g and 0.804 mmol/g, respectively. The adsorption isotherm fits well with Langmuir model and the adsorption kinetic can be described by film diffusion and chemical reaction model. The membrane can retain 95% of its initial capacity after cycling 10 times. Both the sorption capacity and kinetic coefficients are high when comparing with other sorbents for either carbendazim or phenol, demonstrating that the electrospun PIM-1 is a good adsorbent.

Rheological study of copper and copper grapheme feedstock for powder injection molding

NASA Astrophysics Data System (ADS)

Azaman, N. Emira Binti; Rafi Raza, M.; Muhamad, N.; Niaz Akhtar, M.; Bakar Sulong, A.

2017-01-01

Heatsink is one of the solution to optimize the performance of smart electronic devices. Copper and its composites are helping the electronic industry to solve the heating problem. Copper-graphene heat sink material with enhanced thermal conductivity is the ultimate goal.Powder injection molding (PIM) has advantages of high precision and production rate, complex shape, low cost and suitabality for metal and cremics.PIM consists of four sub sequential steps; feedstock preparation, molding, debinding and sintering. Feedstock preparation is a critical step in PIM process. Any deficiency at this stage cannot be recovered at latter stages. Therefore, this research was carried out to investigate the injectability of copper and copper graphene composite using PIM. PEG based multicomponent binder system was used and the powder loading was upto 7vol.% less than the critical powder loading was used to provide the wettability of the copper powder and graphene nanoplatelets (GNps). Corpper-graphene feedstock contained 0.5vol.% of GNps . To ensure the homogeneity of GNps within feedstock a unique technique was addopted. The microscopic results showed that the feedstock is homogeneous and ready for injection. The viscosity-shear rate relationship was determined and results showed that the addition of 0.5vol.% of GNps in copper has increased the viscosity upto 64.9% at 140˚C than that of pure copper feedstock. This attribute may be due to the large surface area of GNps. On the other hand, by increasing the temperature, viscosity of the feedstock was decreased, which was recommended for PIM. The overall viscosity and share rate lies within the range recommended for PIM process. It is clear that both feedstocks showed pseudo plastic behaviour which is suitable for PIM process. In the pseudo plastic behaviour, the viscosity decreases with the shear rate. It may be due to change in the structure of the solid particles or the binder. The molding results showed that both copper feedstocks were successfully molded and free from the physical defects.

A Review and Update on Papillary Immature Metaplasia of the Uterine Cervix: A Distinct Subset of Low-Grade Squamous Intraepithelial Lesion, Proposing a Possible Cell of Origin.

PubMed

Hong, Soon Auck; Yoo, Su Hyun; Choi, Jene; Robboy, Stanley J; Kim, Kyu-Rae

2018-04-13

- Papillary immature metaplasia (PIM) is a known papillary cervical lesion associated with low-risk human papilloma virus (LR-HPV). - To evaluate additional clinicopathologic features and the HPV genotypes of PIM and discuss the presumptive cell of origin. - A total of 26 PIM cases were evaluated by p16 INK4a , cytokeratin (CK) 7, and CK17 immunohistochemical stainings. Human papilloma virus genotyping was performed, by using HPV DNA Chip, HPV polymerase chain reaction (PCR), and real-time PCR. - Histologically, PIM forms either a papillary mass (n = 21 of 26, 81%) or a slightly elevated/flat plaque (n = 5, 19%). All cases contain variable amounts of mucinous epithelia within the lesions. Koilocytosis was identified in 15 of the 26 cases (58%). Sixteen cases (61%) were associated with LR-HPV (types 6, 11, or 42), but 3 cases (12%) with high-risk (HR) HPV (16, 16/18, and 33), 2 cases (8%) with mixed LR- and HR-HPV (6/16 and 11/58), while 2 cases (8%) were negative, but p16 INK4a immunostaining showed nonblock positivity in all cases. Eight (31%) had high-grade squamous intraepithelial lesion (HSIL) in the adjacent mucosa, 4 (50%) of which showed direct continuity. Identical HPV subtypes were confirmed in separately microdissected cases from PIM and adjacent HSIL. Most lesions (n = 24, 92%) expressed CK17 (reserve cell marker) in a bottom-heavy pattern and CK7 (squamocolumnar junction [SCJ] marker) in a top-heavy pattern, while most cases of low-grade squamous intraepithelial lesion (LSIL) were negative for both markers. - Our results suggest that PIM is a distinct subset of LSIL showing a productive HPV infection, but PIM involves the transformation zone and is proximal to SCJ, while LSIL is mostly from ectocervix or distal to the SCJ.

2012 American Geriatrics Society Beers criteria: enhanced applicability for detecting potentially inappropriate medications in European older adults? A comparison with the Screening Tool of Older Person's Potentially Inappropriate Prescriptions.

PubMed

Blanco-Reina, Encarnación; Ariza-Zafra, Gabriel; Ocaña-Riola, Ricardo; León-Ortiz, Matilde

2014-07-01

To determine the prevalence of potentially inappropriate medications (PIMs) and related factors through a comparative analysis of the Screening Tool of Older Person's Potentially Inappropriate Prescriptions (STOPP), the 2003 Beers criteria, and the 2012 AGS update of the Beers criteria. Cross-sectional. Primary care. Community-dwelling persons aged 65 and older who live on the island of Lanzarote, Spain (N = 407). Sociodemographic characteristics; independence in activities of daily living; cognitive function; Geriatric Depression Scale; clinical diagnoses; and complete data on indication, dosage, and length of drug treatments. One thousand eight hundred seventh-two prescriptions were examined, and the rate of PIMs was assessed with the three criteria. The primary endpoint was the percentage of participants receiving at least one PIM. Multivariate logistic regression was used to examine the factors related to PIMs. Potentially inappropriate medications were present in 24.3%, 35.4%, and 44% of participants, according to the 2003 Beers criteria, STOPP, and 2012 Beers criteria, respectively. The profile of PIMs was also different (the most frequent being benzodiazepines in both Beers criteria lists and aspirin in the STOPP). The number of drugs was associated with risk of prescribing PIMs in all three models, as was the presence of a psychological disorder in the 2003 Beers criteria (odds ratio (OR) = 2.07, 95% confidence interval (CI) = 1.26-3.40) and the 2012 Beers criteria (OR = 2.91, 95% CI = 1.83-4.66). The kappa for degree of agreement between STOPP and the 2012 Beers criteria was 0.35 (95% CI = 0.25-0.44). The 2012 Beers criteria detected the highest number of PIMs, and given the scant overlapping with the STOPP criteria, the use of both tools may be seen as complementary. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: a systematic review and thematic synthesis.

PubMed

Anderson, Kristen; Stowasser, Danielle; Freeman, Christopher; Scott, Ian

2014-12-08

To synthesise qualitative studies that explore prescribers' perceived barriers and enablers to minimising potentially inappropriate medications (PIMs) chronically prescribed in adults. A qualitative systematic review was undertaken by searching PubMed, EMBASE, Scopus, PsycINFO, CINAHL and INFORMIT from inception to March 2014, combined with an extensive manual search of reference lists and related citations. A quality checklist was used to assess the transparency of the reporting of included studies and the potential for bias. Thematic synthesis identified common subthemes and descriptive themes across studies from which an analytical construct was developed. Study characteristics were examined to explain differences in findings. All healthcare settings. Medical and non-medical prescribers of medicines to adults. Prescribers' perspectives on factors which shape their behaviour towards continuing or discontinuing PIMs in adults. 21 studies were included; most explored primary care physicians' perspectives on managing older, community-based adults. Barriers and enablers to minimising PIMs emerged within four analytical themes: problem awareness; inertia secondary to lower perceived value proposition for ceasing versus continuing PIMs; self-efficacy in regard to personal ability to alter prescribing; and feasibility of altering prescribing in routine care environments given external constraints. The first three themes are intrinsic to the prescriber (eg, beliefs, attitudes, knowledge, skills, behaviour) and the fourth is extrinsic (eg, patient, work setting, health system and cultural factors). The PIMs examined and practice setting influenced the themes reported. A multitude of highly interdependent factors shape prescribers' behaviour towards continuing or discontinuing PIMs. A full understanding of prescriber barriers and enablers to changing prescribing behaviour is critical to the development of targeted interventions aimed at deprescribing PIMs and reducing the risk of iatrogenic harm. 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.

Identification and prevalence of adverse drug events caused by potentially inappropriate medication in homebound elderly patients: a retrospective study using a nationwide survey in Japan

PubMed Central

Onda, Mitsuko; Imai, Hirohisa; Takada, Yurina; Fujii, Shingo; Shono, Takako; Nanaumi, Yoko

2015-01-01

Objectives A nationwide large-scale survey was conducted to identify the prevalence and causal medications of adverse drug events (ADEs) that are caused by potentially inappropriate medications (PIMs) given to homebound elderly patients, factors associated with ADEs, and measures taken by pharmacists to manage ADEs and their effects on ADEs. Settings A questionnaire was mailed to 3321 pharmacies nationwide. It asked about the details of PIMs and ADEs of up to 5 patients for whom home visits were provided by a pharmacist. Questionnaire forms were filled in by pharmacists who visited the patients. Design and participants Between 23 January and 13 February 2013, comprehensive assessment forms were sent to 3321 pharmacies. Data collected from 1890 pharmacies including data of 4815 patients were analysed and 28 patients of unknown sex were excluded. Their average age was 82.7 years. PIMs were identified based on the 2003 Beers Criteria Japan. Results There were 600 patients who did not provide valid answers regarding the medications. In the remaining 4243 patients, one or more medications that were considered to be PIMs had been prescribed to 48.4% of patients. PIM-induced ADEs were found in 8% of these patients by pharmacists during home visits. The top ADE-inducing medications were strong anticholinergic antihistamines, benzodiazepines, sulpiride and digoxin. The most common ADEs associated with benzodiazepines were frequent lightheadedness, somnolence and sleepiness, which increase the risk of falls and subsequent fractures in elderly patients. The following factors associated with ADEs were identified: sex, pharmacist awareness of prescription issues, frequency of visits and time spent at patients’ homes, and the frequency of detailed checks for patient adverse reactions by pharmacists. Conclusions The PIM prevalence associated with home healthcare in Japan was relatively high, as reported in previous studies. The present study suggests that pharmacists could reduce the incidence of PIMs and consequent ADEs. PMID:26260347

Potentially inappropriate prescribing to older patients in primary care in the Netherlands: a retrospective longitudinal study.

PubMed

Bruin-Huisman, Linette; Abu-Hanna, Ameen; van Weert, Henk C P M; Beers, Erna

2017-07-01

potentially inappropriate prescribing (PIP) is associated with adverse health effects in older patients. PIP comprises prescription of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs). to estimate the prevalence of PIMs and PPOs among older patients in primary care. retrospective longitudinal study. routinely collected data of 182,000 patients of 49 general practitioners (GPs) gathered in the GPs' database of the Academic Medical Center of Amsterdam, the Netherlands. in each studied year, all patients who were aged 65 years and older at 1st January. the prevalence of patients with at least one PIM and patients with at least one PPO was measured in 8 subsequent years (2007-14) by application of the Screening Tool of Older Persons potentially inappropriate Prescriptions (STOPP)/Screening Tool to Alert doctors to Right Treatment (START) criteria. Multivariate logistic regression was used to evaluate trends in the prevalence of PIMs and PPOs over the years. on average, 4,537 patients were included per investigated year. The mean prevalence of ≥1 PIM was 34.7% (range 34.0-35.6%) and of ≥1 PPO 84.8% (range 77.4-90.6%). Examples were the prescription of salicylates without a proper indication and the absence of a therapeutically indicated vitamin D prescription. The prevalence of ≥1 PPOs showed a statistically significant decrease over the investigated years (OR 0.87, P < 0.001), whereas the prevalence of PIMs did not change significantly. this study underscores the need for more attention to medication prescribing to older patients. The prevalence of PIP among older patients in primary care is substantial and the prevalence of PIMs did not decrease over time. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

Space Acceleration Measurement System (SAMS)/Orbital Acceleration Research Experiment (OARE)

NASA Technical Reports Server (NTRS)

Hakimzadeh, Roshanak

1998-01-01

The Life and Microgravity Spacelab (LMS) payload flew on the Orbiter Columbia on mission STS-78 from June 20th to July 7th, 1996. The LMS payload on STS-78 was dedicated to life sciences and microgravity experiments. Two accelerometer systems managed by the NASA Lewis Research Center (LERC) flew to support these experiments, namely the Orbital Acceleration Research Experiment (OARE) and the Space Acceleration Measurements System (SAMS). In addition, the Microgravity Measurement Assembly (NOAA), managed by the European Space Research and Technology Center (ESA/ESTEC), and sponsored by NASA, collected acceleration data in support of the experiments on-board the LMS mission. OARE downlinked real-time quasi-steady acceleration data, which was provided to the investigators. The SAMS recorded higher frequency data on-board for post-mission analysis. The MMA downlinked real-time quasi-steady as well as higher frequency acceleration data, which was provided to the investigators. The Principal Investigator Microgravity Services (PIMS) project at NASA LERC supports principal investigators of microgravity experiments as they evaluate the effects of varying acceleration levels on their experiments. A summary report was prepared by PIMS to furnish interested experiment investigators with a guide to evaluate the acceleration environment during STS-78, and as a means of identifying areas which require further study. The summary report provides an overview of the STS-78 mission, describes the accelerometer systems flown on this mission, discusses some specific analyses of the accelerometer data in relation to the various activities which occurred during the mission, and presents plots resulting from these analyses as a snapshot of the environment during the mission. Numerous activities occurred during the STS-78 mission that are of interest to the low-gravity community. Specific activities of interest during this mission were crew exercise, radiator deployment, Vernier Reaction Control System (VRCS) reboost, venting operations, Flight Control System (FCS) checkout, rack excitation, operation of the Life Sciences Laboratory Equipment Refrigerator/Freezer (LSLE R/F), operation of the JSC Projects Centrifuge, crew sleep, and attitude changes. The low-gravity environment related to these activities is discussed in the summary report.

Structure-based design of novel quinoxaline-2-carboxylic acids and analogues as Pim-1 inhibitors.

PubMed

Oyallon, Bruno; Brachet-Botineau, Marie; Logé, Cédric; Bonnet, Pascal; Souab, Mohamed; Robert, Thomas; Ruchaud, Sandrine; Bach, Stéphane; Berthelot, Pascal; Gouilleux, Fabrice; Viaud-Massuard, Marie-Claude; Denevault-Sabourin, Caroline

2018-05-11

We identified a new series of quinoxaline-2-carboxylic acid derivatives, targeting the human proviral integration site for Moloney murine leukemia virus-1 (HsPim-1) kinase. Seventeen analogues were synthesized providing useful insight into structure-activity relationships studied. Docking studies realized in the ATP pocket of HsPim-1 are consistent with an unclassical binding mode of these inhibitors. The lead compound 1 was able to block HsPim-1 enzymatic activity at nanomolar concentrations (IC 50 of 74 nM), with a good selectivity profile against a panel of mammalian protein kinases. In vitro studies on the human chronic myeloid leukemia cell line KU812 showed an antitumor activity at micromolar concentrations. As a result, compound 1 represents a promising lead for the design of novel anticancer targeted therapies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The effectiveness of psychoanalytic-interactional psychotherapy in borderline personality disorder.

PubMed

Leichsenring, Falk; Masuhr, Oliver; Jaeger, Ulrich; Dally, Andreas; Streeck, Ulrich

2010-01-01

Different methods are available for the psychotherapeutic treatment of patients with severe personality disorders. In Germany, a special form of dynamically oriented therapy called psychoanalytic-interactional psychotherapy or method (PiM) has been clinically applied for many years. PiM was derived from psychoanalytic therapy and has been specifically adapted for the treatment of severely disordered patients, for example, patients with borderline personality disorders, prepsychotic disorders, addictions, and perversions. In a naturalistic study, the effectiveness of PiM was tested in a sample of patients with borderline personality disorders (N = 132). The patients were treated in the Clinic Tiefenbrunn near Göettingen. Standardized, reliable, and valid diagnostic instruments were used to study the treatment effects. According to the results, PiM achieved significant improvements in target symptoms, general symptoms, interpersonal problems, and contentedness with life. The results are discussed with regard to the treatment of severely disordered patients.

A review comparing cathodic arcs and high power impulse magnetron sputtering (HiPIMS)

DOE PAGES

Anders, André

2014-09-02

In this study, high power impulse magnetron sputtering (HiPIMS) has been in the center of attention over the last years as it is an emerging physical vapor deposition (PVD) technology that combines advantages of magnetron sputtering with various forms of energetic deposition of films such as ion plating and cathodic arc plasma deposition. It should not come at a surprise that many extension and variations of HiPIMS make use, intentionally or unintentionally, of previously discovered approaches to film processing such as substrate surface preparation by metal ion sputtering and phased biasing for film texture and stress control. Therefore, in thismore » review, an overview is given on some historical developments and features of cathodic arc and HiPIMS plasmas, showing commonalities and differences. To limit the scope, emphasis is put on plasma properties, as opposed to surveying the vast literature on specific film materials and their properties.« less

High-Pressure CO2 Sorption in Polymers of Intrinsic Microporosity under Ultrathin Film Confinement.

PubMed

Ogieglo, Wojciech; Ghanem, Bader; Ma, Xiaohua; Wessling, Matthias; Pinnau, Ingo

2018-04-04

Ultrathin microporous polymer films are pertinent to the development and further spread of nanotechnology with very promising potential applications in molecular separations, sensors, catalysis, or batteries. Here, we report high-pressure CO 2 sorption in ultrathin films of several chemically different polymers of intrinsic microporosity (PIMs), including the prototypical PIM-1. Films with thicknesses down to 7 nm were studied using interference-enhanced in situ spectroscopic ellipsometry. It was found that all PIMs swell much more than non-microporous polystyrene and other high-performance glassy polymers reported previously. Furthermore, chemical modifications of the parent PIM-1 strongly affected the swelling magnitude. By investigating the behavior of relative refractive index, n rel , it was possible to study the interplay between micropores filling and matrix expansion. Remarkably, all studied PIMs showed a maximum in n rel at swelling of 2-2.5% indicating a threshold point above which the dissolution in the dense matrix started to dominate over sorption in the micropores. At pressures above 25 bar, all PIMs significantly plasticized in compressed CO 2 and for the ones with the highest affinity to the penetrant, a liquidlike mixing typical for rubbery polymers was observed. Reduction of film thickness below 100 nm revealed pronounced nanoconfinement effects and resulted in a large swelling enhancement and a quick loss of the ultrarigid character. On the basis of the partial molar volumes of the dissolved CO 2 , the effective reduction of the T g was estimated to be ∼200 °C going from 128 to 7 nm films.

Pilot test of a home-based program to prevent perceived insufficient milk.

PubMed

Wood, Natsuko K; Sanders, Elizabeth A; Lewis, Frances M; Woods, Nancy F; Blackburn, Susan T

2017-12-01

Although the World Health Organization and American Academy of Pediatrics recommend exclusive breastfeeding for the first six months, only 22% of U.S. mothers do so. Mothers' perceived insufficient milk (PIM) is the primary reason for breastfeeding discontinuation globally. There are two changeable causes of PIM: (1) mothers' misinterpretation of their infant's behavior, and (2) mothers' lack of confidence in their ability to breastfeed. The purpose of this study was to evaluate the short-term effect of a home-based intervention designed to prevent and/or reduce PIM. A mixed-methods, single-group, pretest-midtest-posttest design was used for evaluating a home-based breastfeeding program. The program was implemented during three 1.0- to 1.5-h home intervention sessions at 6, 13, and 27 days postpartum, delivered to 14 dyads of breastfeeding mothers and their full-term singleton infants. We found significant increases over time in mothers' sensitivity to infant behavior and breastfeeding self-efficacy as well as significant decreased attribution of infant crying to PIM. Exit interviews indicated that the program was accepted by participating mothers. This is the first intervention study that has directly targeted the causes of PIM. The home-based intervention has the potential to add to maternal competencies both in correctly assessing their infants' behavior, thereby preventing erroneous attribution of infant behavior to PIM, as well as simultaneously bolstering maternal confidence in breastfeeding skills. By building maternal competencies, the home-based intervention has a longer-range potential to prevent breastfeeding discontinuation. Further evaluation is warranted. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Potentially inappropriate medication: Association between the use of antidepressant drugs and the subsequent risk for dementia.

PubMed

Heser, Kathrin; Luck, Tobias; Röhr, Susanne; Wiese, Birgitt; Kaduszkiewicz, Hanna; Oey, Anke; Bickel, Horst; Mösch, Edelgard; Weyerer, Siegfried; Werle, Jochen; Brettschneider, Christian; König, Hans-Helmut; Fuchs, Angela; Pentzek, Michael; van den Bussche, Hendrik; Scherer, Martin; Maier, Wolfgang; Riedel-Heller, Steffi G; Wagner, Michael

2018-01-15

Potentially inappropriate medication (PIM) is associated with an increased risk for detrimental health outcomes in elderly patients. Some antidepressant drugs are considered as PIM, but previous research on the association between antidepressants and subsequent dementia has been inconclusive. Therefore, we investigated whether the intake of antidepressants, particularly of those considered as PIM according to the Priscus list, would predict incident dementia. We used data of a prospective cohort study of non-demented primary care patients (n = 3239, mean age = 79.62) to compute Cox proportional hazards models. The risk for subsequent dementia was estimated over eight follow-ups up to 12 years depending on antidepressant intake and covariates. The intake of antidepressants was associated with an increased risk for subsequent dementia (HR = 1.53, 95% CI: 1.16-2.02, p = .003; age-, sex-, education-adjusted). PIM antidepressants (HR = 1.49, 95% CI: 1.06-2.10, p = .021), but not other antidepressants (HR = 1.04, 95% CI: 0.66-1.66, p = .863), were associated with an increased risk for subsequent dementia (in age-, sex-, education-, and depressive symptoms adjusted models). Significant associations disappeared after global cognition at baseline was controlled for. Methodological limitations such as selection biases and self-reported drug assessments might have influenced the results. Only antidepressants considered as PIM were associated with an increased subsequent dementia risk. Anticholinergic effects might explain this relationship. The association disappeared after the statistical control for global cognition at baseline. Nonetheless, physicians should avoid the prescription of PIM antidepressants in elderly patients whenever possible. Copyright © 2017 Elsevier B.V. All rights reserved.

Eco-friendly synthesis of novel cyanopyridine derivatives and their anticancer and PIM-1 kinase inhibitory activities.

PubMed

Abouzid, Khaled A M; Al-Ansary, Ghada H; El-Naggar, Abeer M

2017-07-07

Targeting Pim-1 kinase recently proved to be profitable for conquering cancer proliferation. In the current study, we report the design, synthesis and biological evaluation of two novel series of 2-amino cyanopyridine series (5a-g) and 2-oxocyanopyridine series (6a-g) targeting Pim-1 kinase. All of the newly synthesized compounds were evaluated for their in vitro anticancer activity against a panel of three cell lines, namely, the liver cancer cell line (HepG2), the colon cancer cell line (HCT-116) and the breast cancer cell line (MCF-7). Most of the compounds showed good to moderate anti-proliferative activity against HepG2 and HCT-116 cell lines while only few compounds showed significant cytotoxic activity against MCF-7 cell line. Further, the Pim-1 kinase inhibitory activity for the two series was evaluated where most of the tested compounds showed marked Pim-1 kinase inhibitory activity (26%-89%). Moreover, determination of the IC 50 values unraveled very potent molecules in the submicromolar range where compound 6c possessed an IC 50 value of 0.94 μM. Moreover, apoptosis studies were conducted on the most potent compound 6c to evaluate the proapoptotic potential of our compounds. Interestingly, it induced the level of active caspase 3 and boosted the Bax/Bcl2 ratio 22704 folds in comparison to the control. Finally, a molecular docking study was conducted to reveal the probable interaction with the Pim-1 kinase active site. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Enhanced properties of tungsten thin films deposited with a novel HiPIMS approach

NASA Astrophysics Data System (ADS)

Velicu, Ioana-Laura; Tiron, Vasile; Porosnicu, Corneliu; Burducea, Ion; Lupu, Nicoleta; Stoian, George; Popa, Gheorghe; Munteanu, Daniel

2017-12-01

Despite the tremendous potential for industrial use of tungsten (W), very few studies have been reported so far on controlling and tailoring the properties of W thin films obtained by physical vapor deposition techniques and, even less, for those deposited by High Power Impulse Magnetron Sputtering (HiPIMS). This study presents results on the deposition process and properties characterization of nanocrystalline W thin films deposited on silicon and molybdenum substrates (100 W average sputtering power) by conventional dc magnetron sputtering (dcMS) and HiPIMS techniques. Topological, structural, mechanical and tribological properties of the deposited thin films were investigated. It was found that in HiPIMS, both deposition process and coatings properties may be optimized by using an appropriate magnetic field configuration and pulsing design. Compared to the other deposited samples, the W films grown in multi-pulse (5 × 3 μs) HiPIMS assisted by an additional magnetic field, created with a toroidal-shaped permanent magnet placed in front of the magnetron cathode, show significantly enhanced properties, such as: smoother surfaces, higher homogeneity and denser microstructure, higher hardness and Young's modulus values, better adhesion to the silicon substrate and lower coefficient of friction. Mechanical behaviour and structural changes are discussed based on plasma diagnostics results.

Discovery of novel Pim-1 kinase inhibitors by a hierarchical multistage virtual screening approach based on SVM model, pharmacophore, and molecular docking.

PubMed

Ren, Ji-Xia; Li, Lin-Li; Zheng, Ren-Lin; Xie, Huan-Zhang; Cao, Zhi-Xing; Feng, Shan; Pan, You-Li; Chen, Xin; Wei, Yu-Quan; Yang, Sheng-Yong

2011-06-27

In this investigation, we describe the discovery of novel potent Pim-1 inhibitors by employing a proposed hierarchical multistage virtual screening (VS) approach, which is based on support vector machine-based (SVM-based VS or SB-VS), pharmacophore-based VS (PB-VS), and docking-based VS (DB-VS) methods. In this approach, the three VS methods are applied in an increasing order of complexity so that the first filter (SB-VS) is fast and simple, while successive ones (PB-VS and DB-VS) are more time-consuming but are applied only to a small subset of the entire database. Evaluation of this approach indicates that it can be used to screen a large chemical library rapidly with a high hit rate and a high enrichment factor. This approach was then applied to screen several large chemical libraries, including PubChem, Specs, and Enamine as well as an in-house database. From the final hits, 47 compounds were selected for further in vitro Pim-1 inhibitory assay, and 15 compounds show nanomolar level or low micromolar inhibition potency against Pim-1. In particular, four of them were found to have new scaffolds which have potential for the chemical development of Pim-1 inhibitors.

Composite targets in HiPIMS plasmas: Correlation of in-vacuum XPS characterization and optical plasma diagnostics

NASA Astrophysics Data System (ADS)

Layes, Vincent; Monje, Sascha; Corbella, Carles; Schulz-von der Gathen, Volker; von Keudell, Achim; de los Arcos, Teresa

2017-05-01

In-vacuum characterization of magnetron targets after High Power Impulse Magnetron Sputtering (HiPIMS) has been performed by X-ray photoelectron spectroscopy (XPS). Al-Cr composite targets (circular, 50 mm diameter) mounted in two different geometries were investigated: an Al target with a small Cr disk embedded at the racetrack position and a Cr target with a small Al disk embedded at the racetrack position. The HiPIMS discharge and the target surface composition were characterized in parallel for low, intermediate, and high power conditions, thus covering both the Ar-dominated and the metal-dominated HiPIMS regimes. The HiPIMS plasma was investigated using optical emission spectroscopy and fast imaging using a CCD camera; the spatially resolved XPS surface characterization was performed after in-vacuum transfer of the magnetron target to the XPS chamber. This parallel evaluation showed that (i) target redeposition of sputtered species was markedly more effective for Cr atoms than for Al atoms; (ii) oxidation at the target racetrack was observed even though the discharge ran in pure Ar gas without O2 admixture, the oxidation depended on the discharge power and target composition; and (iii) a bright emission spot fixed on top of the inserted Cr disk appeared for high power conditions.

[Identifying potentially inappropriate prescriptions in patients over 65 years-old using original Beers criteria and their Spanish adaptation].

PubMed

Pastor Cano, Josep; Aranda García, Ana; Gascón Cánovas, Juan José; Sánchez Ruiz, José Francisco; Rausell Rausell, Víctor José; Tobaruela Soto, Mariana

2018-02-01

To compare the detection of potentially inappropriate medication (PIM) using the original Beers criteria, a global reference for evaluating prescriptions in the elderly, and their Spanish version. Retrospective observational study LOCATION: A Primary Care area in the province of Murcia, Spain. A total of 7,856 subjects aged 65 and over, with at least one drug prescribed in a Primary Care Area of Spain during study period. Illnesses and treatments registered in the Primary Care computerised medical history of patients were analysed during a 12month study period (2012). The original Beers criteria and their Spanish adaptation were used to evaluate PIM, considering both sets of criteria overall, and individually. The median age of the patients was 76.0years, with the majority females (56.6%). Patients received a median of 13 active substances and 66 medical prescriptions. The percentage of patients prescribed PIM ranged from 44.8% according to the original Beers criteria to 49.4% with the Spanish adaptation. PIMs are frequent in our context. The original Beers criteria, if not adapted to the local drug catalogue, underestimated the frequency of PIM in the elderly population studied. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Space Technology for Medical Aids

NASA Technical Reports Server (NTRS)

1982-01-01

Under one of the earliest contracts awarded in the Apollo lunar landing program, Parker Hannifin Corporation developed and produced equipment for controlling the flow of propellants into the mammoth engines of the Saturn moonbooster. Today, Parker is supplying the huge valves that control propellant flow from the Space Shuttle's external fuel tank to the engines of the Shuttle Orbiter as well as the "peanut valve," named for its small size. In 1977, NASA, recognizing the company's special expertise in miniature systems, asked Parker to participate in the development of an implantable artificial sphincter for control of urinary incontinence. The company's peanut valve experience provided an ideal base for a new biomedical project, the Programmable Implantable Medication System (PIMS) for continuous, computer-directed delivery of precisely metered medication -- insulin, for example -- within a patient's body. The work on PIMS also inspired development of Micromed, a related programmable medication device for external, rather than implantable use. The Biomedical Products Division has also applied its fluid handling expertise to a drugless therapy system called Cryomax for the treatment of such disorders as rheumatoid arthritis and lupus.

How Do Organic Vapors Swell Ultrathin Films of Polymer of Intrinsic Microporosity PIM-1?

PubMed

Ogieglo, Wojciech; Rahimi, Khosorov; Rauer, Sebastian Bernhard; Ghanem, Bader; Ma, Xiaohua; Pinnau, Ingo; Wessling, Matthias

2017-07-27

Dynamic sorption of ethanol and toluene vapor into ultrathin supported films of polymer of intrinsic microporosity PIM-1 down to a thickness of 6 nm are studied with a combination of in situ spectroscopic ellipsometry and in situ X-ray reflectivity. Both ethanol and toluene significantly swell the PIM-1 matrix and, at the same time, induce persistent structural relaxations of the frozen-in glassy PIM-1 morphology. For ethanol below 20 nm, three effects were identified. First, the swelling magnitude at high vapor pressures is reduced by about 30% as compared to that of thicker films. Second, at low penetrant activities (below 0.3p/p 0 ), films below 20 nm are able to absorb slightly more penetrant as compared with thicker films despite a similar swelling magnitude. Third, for the ultrathin films, the onset of the dynamic penetrant-induced glass transition P g has been found to shift to higher values, indicating higher resistance to plasticization. All of these effects are consistent with a view where immobilization of the superglassy PIM-1 at the substrate surface leads to an arrested, even more rigid, and plasticization-resistant, yet still very open, microporous structure. PIM-1 in contact with the larger and more condensable toluene shows very complex, heterogeneous swelling dynamics, and two distinct penetrant-induced relaxation phenomena, probably associated with the film outer surface and the bulk, are detected. Following the direction of the penetrant's diffusion, the surface seems to plasticize earlier than the bulk, and the two relaxations remain well separated down to 6 nm film thickness, where they remarkably merge to form just a single relaxation.

Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia-lymphoma cells.

PubMed

Taniguchi, Hiroaki; Hasegawa, Hiroo; Sasaki, Daisuke; Ando, Koji; Sawayama, Yasushi; Imanishi, Daisuke; Taguchi, Jun; Imaizumi, Yoshitaka; Hata, Tomoko; Tsukasaki, Kunihiro; Uno, Naoki; Morinaga, Yoshitomo; Yanagihara, Katsunori; Miyazaki, Yasushi

2014-12-01

Adult T-cell leukemia-lymphoma (ATL), an aggressive neoplasm etiologically associated with HTLV-1, is a chemoresistant malignancy. Heat shock protein 90 (HSP90) is involved in folding and functions as a chaperone for multiple client proteins, many of which are important in tumorigenesis. In this study, we examined NVP-AUY922 (AUY922), a second generation isoxazole-based non-geldanamycin HSP90 inhibitor, and confirmed its effects on survival of ATL-related cell lines. Analysis using FACS revealed that AUY922 induced cell-cycle arrest and apoptosis; it also inhibited the growth of primary ATL cells, but not of normal PBMCs. AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin. Interestingly, AUY922 induced downregulation of the proviral integration site for Moloney murine leukemia virus (PIM) in ATL cells. The PIM family (PIM-1, -2, -3) is made up of oncogenes that encode a serine/threonine protein kinase family. As PIM kinases have multiple functions involved in cell proliferation, survival, differentiation, apoptosis, and tumorigenesis, their downregulation could play an important role in AUY922-induced death of ATL cells. In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines. Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia–lymphoma cells

PubMed Central

Taniguchi, Hiroaki; Hasegawa, Hiroo; Sasaki, Daisuke; Ando, Koji; Sawayama, Yasushi; Imanishi, Daisuke; Taguchi, Jun; Imaizumi, Yoshitaka; Hata, Tomoko; Tsukasaki, Kunihiro; Uno, Naoki; Morinaga, Yoshitomo; Yanagihara, Katsunori; Miyazaki, Yasushi

2014-01-01

Adult T-cell leukemia–lymphoma (ATL), an aggressive neoplasm etiologically associated with HTLV-1, is a chemoresistant malignancy. Heat shock protein 90 (HSP90) is involved in folding and functions as a chaperone for multiple client proteins, many of which are important in tumorigenesis. In this study, we examined NVP-AUY922 (AUY922), a second generation isoxazole-based non-geldanamycin HSP90 inhibitor, and confirmed its effects on survival of ATL-related cell lines. Analysis using FACS revealed that AUY922 induced cell-cycle arrest and apoptosis; it also inhibited the growth of primary ATL cells, but not of normal PBMCs. AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin. Interestingly, AUY922 induced downregulation of the proviral integration site for Moloney murine leukemia virus (PIM) in ATL cells. The PIM family (PIM-1, -2, -3) is made up of oncogenes that encode a serine/threonine protein kinase family. As PIM kinases have multiple functions involved in cell proliferation, survival, differentiation, apoptosis, and tumorigenesis, their downregulation could play an important role in AUY922-induced death of ATL cells. In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines. Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target. PMID:25263741

Rejuvenation of human cardiac progenitor cells with Pim-1 kinase.

PubMed

Mohsin, Sadia; Khan, Mohsin; Nguyen, Jonathan; Alkatib, Monique; Siddiqi, Sailay; Hariharan, Nirmala; Wallach, Kathleen; Monsanto, Megan; Gude, Natalie; Dembitsky, Walter; Sussman, Mark A

2013-10-25

Myocardial function is enhanced by adoptive transfer of human cardiac progenitor cells (hCPCs) into a pathologically challenged heart. However, advanced age, comorbidities, and myocardial injury in patients with heart failure constrain the proliferation, survival, and regenerative capacity of hCPCs. Rejuvenation of senescent hCPCs will improve the outcome of regenerative therapy for a substantial patient population possessing functionally impaired stem cells. Reverse phenotypic and functional senescence of hCPCs by ex vivo modification with Pim-1. C-kit-positive hCPCs were isolated from heart biopsy samples of patients undergoing left ventricular assist device implantation. Growth kinetics, telomere lengths, and expression of cell cycle regulators showed significant variation between hCPC isolated from multiple patients. Telomere length was significantly decreased in hCPC with slow-growth kinetics concomitant with decreased proliferation and upregulation of senescent markers compared with hCPC with fast-growth kinetics. Desirable youthful characteristics were conferred on hCPCs by genetic modification using Pim-1 kinase, including increases in proliferation, telomere length, survival, and decreased expression of senescence markers. Senescence characteristics of hCPCs are ameliorated by Pim-1 kinase resulting in rejuvenation of phenotypic and functional properties. hCPCs show improved cellular properties resulting from Pim-1 modification, but benefits were more pronounced in hCPC with slow-growth kinetics relative to hCPC with fast-growth kinetics. With the majority of patients with heart failure presenting advanced age, infirmity, and impaired regenerative capacity, the use of Pim-1 modification should be incorporated into cell-based therapeutic approaches to broaden inclusion criteria and address limitations associated with the senescent phenotype of aged hCPC.

Rejuvenation of Human Cardiac Progenitor Cells With Pim-1 Kinase

PubMed Central

Mohsin, Sadia; Khan, Mohsin; Nguyen, Jonathan; Alkatib, Monique; Siddiqi, Sailay; Hariharan, Nirmala; Wallach, Kathleen; Monsanto, Megan; Gude, Natalie; Dembitsky, Walter; Sussman, Mark A.

2014-01-01

Rationale Myocardial function is enhanced by adoptive transfer of human cardiac progenitor cells (hCPCs) into a pathologically challenged heart. However, advanced age, comorbidities, and myocardial injury in patients with heart failure constrain the proliferation, survival, and regenerative capacity of hCPCs. Rejuvenation of senescent hCPCs will improve the outcome of regenerative therapy for a substantial patient population possessing functionally impaired stem cells. Objective Reverse phenotypic and functional senescence of hCPCs by ex vivo modification with Pim-1. Methods and Results C-kit–positive hCPCs were isolated from heart biopsy samples of patients undergoing left ventricular assist device implantation. Growth kinetics, telomere lengths, and expression of cell cycle regulators showed significant variation between hCPC isolated from multiple patients. Telomere length was significantly decreased in hCPC with slow-growth kinetics concomitant with decreased proliferation and upregulation of senescent markers compared with hCPC with fast-growth kinetics. Desirable youthful characteristics were conferred on hCPCs by genetic modification using Pim-1 kinase, including increases in proliferation, telomere length, survival, and decreased expression of senescence markers. Conclusions Senescence characteristics of hCPCs are ameliorated by Pim-1 kinase resulting in rejuvenation of phenotypic and functional properties. hCPCs show improved cellular properties resulting from Pim-1 modification, but benefits were more pronounced in hCPC with slow-growth kinetics relative to hCPC with fast-growth kinetics. With the majority of patients with heart failure presenting advanced age, infirmity, and impaired regenerative capacity, the use of Pim-1 modification should be incorporated into cell-based therapeutic approaches to broaden inclusion criteria and address limitations associated with the senescent phenotype of aged hCPC. PMID:24044948

Can generic paediatric mortality scores calculated 4 hours after admission be used as inclusion criteria for clinical trials?

PubMed Central

Leteurtre, Stéphane; Leclerc, Francis; Wirth, Jessica; Noizet, Odile; Magnenant, Eric; Sadik, Ahmed; Fourier, Catherine; Cremer, Robin

2004-01-01

Introduction Two generic paediatric mortality scoring systems have been validated in the paediatric intensive care unit (PICU). Paediatric RISk of Mortality (PRISM) requires an observation period of 24 hours, and PRISM III measures severity at two time points (at 12 hours and 24 hours) after admission, which represents a limitation for clinical trials that require earlier inclusion. The Paediatric Index of Mortality (PIM) is calculated 1 hour after admission but does not take into account the stabilization period following admission. To avoid these limitations, we chose to conduct assessments 4 hours after PICU admission. The aim of the present study was to validate PRISM, PRISM III and PIM at the time points for which they were developed, and to compare their accuracy in predicting mortality at those times with their accuracy at 4 hours. Methods All children admitted from June 1998 to May 2000 in one tertiary PICU were prospectively included. Data were collected to generate scores and predictions using PRISM, PRISM III and PIM. Results There were 802 consecutive admissions with 80 deaths. For the time points for which the scores were developed, observed and predicted mortality rates were significantly different for the three scores (P < 0.01) whereas all exhibited good discrimination (area under the receiver operating characteristic curve ≥0.83). At 4 hours after admission only the PIM had good calibration (P = 0.44), but all three scores exhibited good discrimination (area under the receiver operating characteristic curve ≥0.82). Conclusions Among the three scores calculated at 4 hours after admission, all had good discriminatory capacity but only the PIM score was well calibrated. Further studies are required before the PIM score at 4 hours can be used as an inclusion criterion in clinical trials. PMID:15312217

PIMS: Memristor-Based Processing-in-Memory-and-Storage.

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

Cook, Jeanine

Continued progress in computing has augmented the quest for higher performance with a new quest for higher energy efficiency. This has led to the re-emergence of Processing-In-Memory (PIM) ar- chitectures that offer higher density and performance with some boost in energy efficiency. Past PIM work either integrated a standard CPU with a conventional DRAM to improve the CPU- memory link, or used a bit-level processor with Single Instruction Multiple Data (SIMD) control, but neither matched the energy consumption of the memory to the computation. We originally proposed to develop a new architecture derived from PIM that more effectively addressed energymore » efficiency for high performance scientific, data analytics, and neuromorphic applications. We also originally planned to implement a von Neumann architecture with arithmetic/logic units (ALUs) that matched the power consumption of an advanced storage array to maximize energy efficiency. Implementing this architecture in storage was our original idea, since by augmenting storage (in- stead of memory), the system could address both in-memory computation and applications that accessed larger data sets directly from storage, hence Processing-in-Memory-and-Storage (PIMS). However, as our research matured, we discovered several things that changed our original direc- tion, the most important being that a PIM that implements a standard von Neumann-type archi- tecture results in significant energy efficiency improvement, but only about a O(10) performance improvement. In addition to this, the emergence of new memory technologies moved us to propos- ing a non-von Neumann architecture, called Superstrider, implemented not in storage, but in a new DRAM technology called High Bandwidth Memory (HBM). HBM is a stacked DRAM tech- nology that includes a logic layer where an architecture such as Superstrider could potentially be implemented.« less

Use of the Screening Tool of Older Persons' Prescriptions (STOPP) and the Screening Tool to Alert doctors to the Right Treatment (START) in hospitalised older people.

PubMed

Manias, Elizabeth; Kusljic, Snezana; Lam, Di-Luu

2015-12-01

To determine the prevalence and nature of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) in patients aged 65 years and over. A retrospective clinical audit was undertaken (N = 200) in an Australian metropolitan teaching hospital. The prevalence of at least one PIM was 51% (n = 101) whereas the prevalence of at least one PPO was 74% (n = 147). The most common PIM was prescribing aspirin to patients with no history of coronary, cerebral or peripheral arterial disease or occlusive arterial events. The most commonly detected PPO was the failure to prescribe statins to patients with a documented history of coronary, cerebral or peripheral vascular disease. Overall, 80 (24%) of the 335 PIMs identified were possibly associated with an adverse clinical outcome experienced by patients. Inappropriate prescribing continues to be a problem as shown by complexities associated with the risk-benefit trade-offs of managing medications in older patients. © 2014 AJA Inc.

The potential of organic polymer-based hydrogen storage materials.

PubMed

Budd, Peter M; Butler, Anna; Selbie, James; Mahmood, Khalid; McKeown, Neil B; Ghanem, Bader; Msayib, Kadhum; Book, David; Walton, Allan

2007-04-21

The challenge of storing hydrogen at high volumetric and gravimetric density for automotive applications has prompted investigations into the potential of cryo-adsorption on the internal surface area of microporous organic polymers. A range of Polymers of Intrinsic Microporosity (PIMs) has been studied, the best PIM to date (a network-PIM incorporating a triptycene subunit) taking up 2.7% H(2) by mass at 10 bar/77 K. HyperCrosslinked Polymers (HCPs) also show promising performance as H(2) storage materials, particularly at pressures >10 bar. The N(2) and H(2) adsorption behaviour at 77 K of six PIMs and a HCP are compared. Surface areas based on Langmuir plots of H(2) adsorption at high pressure are shown to provide a useful guide to hydrogen capacity, but Langmuir plots based on low pressure data underestimate the potential H(2) uptake. The micropore distribution influences the form of the H(2) isotherm, a higher concentration of ultramicropores (pore size <0.7 nm) being associated with enhanced low pressure adsorption.

Programs for Testing Processor-in-Memory Computing Systems

NASA Technical Reports Server (NTRS)

Katz, Daniel S.

2006-01-01

The Multithreaded Microbenchmarks for Processor-In-Memory (PIM) Compilers, Simulators, and Hardware are computer programs arranged in a series for use in testing the performances of PIM computing systems, including compilers, simulators, and hardware. The programs at the beginning of the series test basic functionality; the programs at subsequent positions in the series test increasingly complex functionality. The programs are intended to be used while designing a PIM system, and can be used to verify that compilers, simulators, and hardware work correctly. The programs can also be used to enable designers of these system components to examine tradeoffs in implementation. Finally, these programs can be run on non-PIM hardware (either single-threaded or multithreaded) using the POSIX pthreads standard to verify that the benchmarks themselves operate correctly. [POSIX (Portable Operating System Interface for UNIX) is a set of standards that define how programs and operating systems interact with each other. pthreads is a library of pre-emptive thread routines that comply with one of the POSIX standards.

Deposition of highly textured AlN thin films by reactive high power impulse magnetron sputtering

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

Moreira, Milena A.; Törndahl, Tobias; Katardjiev, Ilia

2015-03-15

Aluminum nitride thin films were deposited by reactive high power impulse magnetron sputtering (HiPIMS) and pulsed direct-current on Si (100) and textured Mo substrates, where the same deposition conditions were used for both techniques. The films were characterized by x-ray diffraction and atomic force microscopy. The results show a pronounced improvement in the AlN crystalline texture for all films deposited by HiPIMS on Si. Already at room temperature, the HiPIMS films exhibited a strong preferred (002) orientation and at 400 °C, no contributions from other orientations were detected. Despite the low film thickness of only 200 nm, an ω-scan full width atmore » half maximum value of 5.1° was achieved on Si. The results are attributed to the high ionization of sputtered material achieved in HiPIMS. On textured Mo, there was no significant difference between the deposition techniques.« less

Study of cobalt mononitride thin films prepared using DC and high power impulse magnetron sputtering

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

Gupta, Rachana, E-mail: dr.rachana.gupta@gmail.com; Pandey, Nidhi; Behera, Layanta

2016-05-23

In this work we studied cobalt mononitride (CoN) thin films deposited using dc magnetron sputtering (dcMS) and high power impulse magnetron sputtering (HiPIMS). A Co target was sputtered using pure N{sub 2} gas alone as the sputtering medium. Obtained long-range structural ordering was studies using x-ray diffraction (XRD), short-range structure using Co L{sub 2,3} and N K absorption edges using soft x-ray absorption spectroscopy (XAS) and the surface morphology using atomic force microscopy (AFM). It was found that HiPIMS deposited films have better long-range ordering, better stoichiometric ratio for mononitride composition and smoother texture as compared to dcMS deposited films.more » In addition, the thermal stability of HiPIMS deposited CoN film seems to be better. On the basis of different type of plasma conditions generated in HiPIMS and dcMS process, obtained results are presented and discussed.« less

Influence of reactive oxygen species during deposition of iron oxide films by high power impulse magnetron sputtering

NASA Astrophysics Data System (ADS)

Stranak, V.; Hubicka, Z.; Cada, M.; Bogdanowicz, R.; Wulff, H.; Helm, C. A.; Hippler, R.

2018-03-01

Iron oxide films were deposited using high power impulse magnetron sputtering (HiPIMS) of an iron cathode in an argon/oxygen gas mixture at different gas pressures (0.5 Pa, 1.5 Pa, and 5.0 Pa). The HiPIMS system was operated at a repetition frequency f  =  100 Hz with a duty cycle of 1%. A main goal is a comparison of film growth during conventional and electron cyclotron wave resonance-assisted HiPIMS. The deposition plasma was investigated by means of optical emission spectroscopy and energy-resolved mass spectrometry. Active oxygen species were detected and their kinetic energy was found to depend on the gas pressure. Deposited films were characterized by means of spectroscopic ellipsometry and grazing incidence x-ray diffraction. Optical properties and crystallinity of as-deposited films were found to depend on the deposition conditions. Deposition of hematite iron oxide films with the HiPIMS-ECWR discharge is attributed to the enhanced production of reactive oxygen species.

FLT3-ITD induces expression of Pim kinases through STAT5 to confer resistance to the PI3K/Akt pathway inhibitors on leukemic cells by enhancing the mTORC1/Mcl-1 pathway.

PubMed

Okada, Keigo; Nogami, Ayako; Ishida, Shinya; Akiyama, Hiroki; Chen, Cheng; Umezawa, Yoshihiro; Miura, Osamu

2018-02-06

FLT3-ITD is the most frequent tyrosine kinase mutation in acute myeloid leukemia (AML) associated with poor prognosis. We previously reported that activation of STAT5 confers resistance to PI3K/Akt inhibitors on the FLT3-ITD-positive AML cell line MV4-11 and 32D cells driven by FLT3-ITD (32D/ITD) but not by FLT3 mutated in the tyrosine kinase domain (32D/TKD). Here, we report the involvement of Pim kinases expressed through STAT5 activation in acquisition of this resistance. The specific pan-Pim kinase inhibitor AZD1208 as well as PIM447 in combination with the PI3K inhibitor GDC-0941 or the Akt inhibitor MK-2206 cooperatively downregulated the mTORC1/4EBP1 pathway, formation of the eIF4E/eIF4G complex, and Mcl-1 expression leading to activation of Bak and Bax to induce caspase-dependent apoptosis synergistically in these cells. These cooperative effects were enhanced or inhibited by knock down of mTOR or expression of its activated mutant, respectively. Overexpression of Mcl-1 conferred the resistance on 32D/ITD cells to combined inhibition of the PI3K/Akt pathway and Pim kinases, while the Mcl-1-specific BH3 mimetic A-1210477 conquered the resistance of MV4-11 cells to GDC-0941. Furthermore, overexpression of Pim-1 in 32D/TKD enhanced the mTORC1/Mcl-1 pathway and partially protected it from the PI3K/Akt inhibitors or the FLT3 inhibitor gilteritinib to confer the resistance to PI3K/Akt inhibitors. Finally, AZD1208 and GDC-0941 cooperatively inhibited the mTORC1/Mcl-1 pathway and reduced viable cell numbers of primary AML cells from some FLT3-ITD positive cases. Thus, Pim kinases may protect the mTORC1/4EBP1/Mcl-1 pathway to confer the resistance to the PI3K/Akt inhibitors on FLT3-ITD cells and represent promising therapeutic targets.

Severe drug interactions and potentially inappropriate medication usage in elderly cancer patients.

PubMed

Alkan, Ali; Yaşar, Arzu; Karcı, Ebru; Köksoy, Elif Berna; Ürün, Muslih; Şenler, Filiz Çay; Ürün, Yüksel; Tuncay, Gülseren; Ergün, Hakan; Akbulut, Hakan

2017-01-01

Due to more comorbidities, polypharmacy is common in elderly patients and drug interactions are inevitable. It is also challenging to treat an elderly patient with a diagnosis of cancer. Prevalence and clinical impacts of drug interactions and using potentially inappropriate medications (PIMs) have been studied in geriatric patients. However, these are not well defined in oncology practice. The purpose of this study is to define the prevalence of PIMs and severe drug interactions (SDIs) in elderly cancer patients and investigate the factors associated with them. Patients more than 65 years of age in both inpatient and outpatient clinics were evaluated. Patient, disease characteristics, and medications used were collected by self reports and medical records. Drug interactions were checked with Lexicomp® and PIM was defined with 2012 update of Beers criteria. Severe drug interactions are defined with category D or X DIs. Logistic regression was used to compute odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between SDIs, PIMs, and clinical parameters. Four hundered and forty-five elderly patients (286 outpatient, 159 inpatient), with a median age of 70 (65-89) were evaluated. SDIs were present in 156 (35.1 %) of patients, 81 (28.3 %), and 75 (47.2 %) for outpatient and inpatients, respectively (p < 0.001). PIMs were present in 117 (26.6 %) of the patients, 40 (14.2 %), and 77(48.4 %) for outpatient and inpatients, respectively (p < 0.001). In multivariate analysis; polypharmacy (≥5 drugs), inpatient status and diagnosis of lung cancer were associated with severe DIs. Polypharmacy, inpatient status, and bad performance score (ECOG 3-4) were associated with PIMs. Nearly one third of the elderly cancer patients are exposed to severe drug interactions and PIMs. Clinicians dealing with elderly cancer patients should be more cautious when prescribing/ planning drugs to this group of patients. More strategies should be developed in this group of patients to minimize the medications prescribed and prevent severe DIs.

Accelerated Evolution of PAK3- and PIM1-like Kinase Gene Families in the Zebra Finch, Taeniopygia guttata

PubMed Central

Kong, Lesheng; Lovell, Peter V.; Heger, Andreas; Mello, Claudio V.; Ponting, Chris P.

2010-01-01

Genes encoding protein kinases tend to evolve slowly over evolutionary time, and only rarely do they appear as recent duplications in sequenced vertebrate genomes. Consequently, it was a surprise to find two families of kinase genes that have greatly and recently expanded in the zebra finch (Taeniopygia guttata) lineage. In contrast to other amniotic genomes (including chicken) that harbor only single copies of p21-activated serine/threonine kinase 3 (PAK3) and proviral integration site 1 (PIM1) genes, the zebra finch genome appeared at first to additionally contain 67 PAK3-like (PAK3L) and 51 PIM1-like (PIM1L) protein kinase genes. An exhaustive analysis of these gene models, however, revealed most to be incomplete, owing to the absence of terminal exons. After reprediction, 31 PAK3L genes and 10 PIM1L genes remain, and all but three are predicted, from the retention of functional sites and open reading frames, to be enzymatically active. PAK3L, but not PIM1L, gene sequences show evidence of recurrent episodes of positive selection, concentrated within structures spatially adjacent to N- and C-terminal protein regions that have been discarded from zebra finch PAK3L genes. At least seven zebra finch PAK3L genes were observed to be expressed in testis, whereas two sequences were found transcribed in the brain, one broadly including the song nuclei and the other in the ventricular zone and in cells resembling Bergmann's glia in the cerebellar Purkinje cell layer. Two PIM1L sequences were also observed to be expressed with broad distributions in the zebra finch brain, one in both the ventricular zone and the cerebellum and apparently associated with glial cells and the other showing neuronal cell expression and marked enrichment in midbrain/thalamic nuclei. These expression patterns do not correlate with zebra finch-specific features such as vocal learning. Nevertheless, our results show how ancient and conserved intracellular signaling molecules can be co-opted, following duplication, thereby resulting in lineage-specific functions, presumably affecting the zebra finch testis and brain. PMID:20237222

The technology and commercial status of powder-injection molding

NASA Astrophysics Data System (ADS)

Bose, Animesh

1995-08-01

The process of powder-injection molding (PIM) is a viable and competitive commercial technique that is being used to process complex-shaped parts of various materials in moderate to high volumes. The hey advantage of the process is its unique ability to combine materials selection flexibility with the complex shape-forming ability of plastics. Although the PIM process has been discussed in the open literature for more than quarter of a century, it has become a commercial reality only during the last decade or so. Currently, there is a tremendous interest in this unique technology throughout the world. As a result, the PIM industry is poised for significant growth.

Insulin Delivery System

NASA Technical Reports Server (NTRS)

1988-01-01

When Programmable Implantable Medication System (PIMS) is implanted in human body, it delivers precise programmed amounts of insulin over long periods of time. Mini-Med Technologies has been refining the Technologies since initial development at APL. The size of a hockey puck, and encased in titanium shell, PIMS holds about 2 1/2 teaspoons of insulin at a programmed basal rate. If a change in measured blood sugar level dictates a different dose, the patient can vary the amount of insulin delivered by holding a small radio transceiver over the implanted system and dialing in a specific program held in the PIMS computer memory. Insulin refills are accomplished approximately 4 times a year by hypodermic needle.

Analysis of Transcriptional Regulation of the Human miR-17-92 Cluster; Evidence for Involvement of Pim-1

PubMed Central

Thomas, Maren; Lange-Grünweller, Kerstin; Hartmann, Dorothee; Golde, Lara; Schlereth, Julia; Streng, Dennis; Aigner, Achim; Grünweller, Arnold; Hartmann, Roland K.

2013-01-01

The human polycistronic miRNA cluster miR-17-92 is frequently overexpressed in hematopoietic malignancies and cancers. Its transcription is in part controlled by an E2F-regulated host gene promoter. An intronic A/T-rich region directly upstream of the miRNA coding region also contributes to cluster expression. Our deletion analysis of the A/T-rich region revealed a strong dependence on c-Myc binding to the functional E3 site. Yet, constructs lacking the 5′-proximal ~1.3 kb or 3′-distal ~0.1 kb of the 1.5 kb A/T-rich region still retained residual specific promoter activity, suggesting multiple transcription start sites (TSS) in this region. Furthermore, the protooncogenic kinase, Pim-1, its phosphorylation target HP1γ and c-Myc colocalize to the E3 region, as inferred from chromatin immunoprecipitation. Analysis of pri-miR-17-92 expression levels in K562 and HeLa cells revealed that silencing of E2F3, c-Myc or Pim-1 negatively affects cluster expression, with a synergistic effect caused by c-Myc/Pim-1 double knockdown in HeLa cells. Thus, we show, for the first time, that the protooncogene Pim-1 is part of the network that regulates transcription of the human miR-17-92 cluster. PMID:23749113

NFκB–Pim-1–Eomesodermin axis is critical for maintaining CD8 T-cell memory quality

PubMed Central

Knudson, Karin M.; Saxena, Vikas; Altman, Amnon; Daniels, Mark A.; Teixeiro, Emma

2017-01-01

T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory. Strikingly, we found that antigen receptor [T-cell receptor (TCR)] signaling regulates this process through expression of the NFκB-dependent kinase proviral integration site for Moloney murine leukemia virus-1 (PIM-1), which in turn regulates NFκB and Eomes. T cells defective in TCR-dependent NFκB signaling were impaired in late expression of Pim-1, Eomes, and CD8 memory. These defects were rescued when TCR-dependent NFκB signaling was restored. We also found that NFκB–Pim-1 signals were required at memory to maintain memory CD8 T-cell longevity, effector function, and Eomes expression. Hence, an NFκB–Pim-1–Eomes axis regulates Eomes levels to maintain memory fitness. PMID:28193872

PIM1 kinase inhibition as a targeted therapy against triple-negative breast tumors with elevated MYC expression.

PubMed

Horiuchi, Dai; Camarda, Roman; Zhou, Alicia Y; Yau, Christina; Momcilovic, Olga; Balakrishnan, Sanjeev; Corella, Alexandra N; Eyob, Henok; Kessenbrock, Kai; Lawson, Devon A; Marsh, Lindsey A; Anderton, Brittany N; Rohrberg, Julia; Kunder, Ratika; Bazarov, Alexey V; Yaswen, Paul; McManus, Michael T; Rugo, Hope S; Werb, Zena; Goga, Andrei

2016-11-01

Triple-negative breast cancer (TNBC), in which cells lack expression of the estrogen receptor (ER), the progesterone receptor (PR) and the ERBB2 (also known as HER2) receptor, is the breast cancer subtype with the poorest outcome. No targeted therapy is available against this subtype of cancer owing to a lack of validated molecular targets. We previously reported that signaling involving MYC-an essential, pleiotropic transcription factor that regulates the expression of hundreds of genes-is disproportionally higher in triple-negative (TN) tumors than in receptor-positive (RP) tumors. Direct inhibition of the oncogenic transcriptional activity of MYC has been challenging to achieve. Here, by conducting a shRNA screen targeting the kinome, we identified PIM1, a non-essential serine-threonine kinase, in a synthetic lethal interaction with MYC. PIM1 expression was higher in TN tumors than in RP tumors and was associated with poor prognosis in patients with hormone- and HER2-negative tumors. Small-molecule PIM kinase inhibitors halted the growth of human TN tumors with elevated MYC expression in patient-derived tumor xenograft (PDX) and MYC-driven transgenic mouse models of breast cancer by inhibiting the oncogenic transcriptional activity of MYC and restoring the function of the endogenous cell cycle inhibitor, p27. Our findings warrant clinical evaluation of PIM kinase inhibitors in patients with TN tumors that have elevated MYC expression.

PIM kinase inhibition presents a novel targeted therapy against triple-negative breast tumors with elevated MYC expression

PubMed Central

Horiuchi, Dai; Camarda, Roman; Zhou, Alicia Y.; Yau, Christina; Momcilovic, Olga; Balakrishnan, Sanjeev; Corella, Alexandra N.; Eyob, Henok; Kessenbrock, Kai; Lawson, Devon A.; Marsh, Lindsey A.; Anderton, Brittany N.; Rohrberg, Julia; Kunder, Ratika; Bazarov, Alexey V.; Yaswen, Paul; McManus, Michael T.; Rugo, Hope S.; Werb, Zena; Goga, Andrei

2017-01-01

Triple-negative breast cancer (TNBC), which lacks the expression of the estrogen, progesterone, and HER2 receptors, represents the breast cancer subtype with the poorest outcome1. No targeted therapy is available against this subtype due to lack of validated molecular targets. We previously reported that MYC signaling is disproportionally elevated in triple-negative (TN) tumors compared to receptor-positive (RP) tumors2. MYC is an essential, pleiotropic transcription factor that regulates the expression of hundreds of genes3. Direct inhibition of oncogenic MYC transcriptional activity has remained challenging4,5. The present study conducted an shRNA screen against all kinases to uncover novel MYC-dependent synthetic lethal combinations, and identified PIM1, a non-essential kinase. Here we demonstrate that PIM1 expression was elevated in TN tumors and was associated with poor prognosis in patients with hormone and HER2 receptor-negative tumors. Small molecule PIM kinase inhibitors halted the growth of human TN tumors with elevated MYC expression in patient-derived tumor xenograft (PDX) and MYC-driven transgenic breast cancer models by inhibiting oncogenic transcriptional activity of MYC while simultaneously restoring the function of the endogenous cell cycle inhibitor, p27. Our findings warrant clinical evaluation of PIM kinase inhibitors in patients with TN tumors that exhibit elevated MYC expression. PMID:27775705

Membranes of Polymers of Intrinsic Microporosity (PIM-1) Modified by Poly(ethylene glycol).

PubMed

Bengtson, Gisela; Neumann, Silvio; Filiz, Volkan

2017-06-05

Until now, the leading polymer of intrinsic microporosity PIM-1 has become quite famous for its high membrane permeability for many gases in gas separation, linked, however, to a rather moderate selectivity. The combination with the hydrophilic and low permeable poly(ethylene glycol) (PEG) and poly(ethylene oxides) (PEO) should on the one hand reduce permeability, while on the other hand enhance selectivity, especially for the polar gas CO₂ by improving the hydrophilicity of the membranes. Four different paths to combine PIM-1 with PEG or poly(ethylene oxide) and poly(propylene oxide) (PPO) were studied: physically blending, quenching of polycondensation, synthesis of multiblock copolymers and synthesis of copolymers with PEO/PPO side chain. Blends and new, chemically linked polymers were successfully formed into free standing dense membranes and measured in single gas permeation of N₂, O₂, CO₂ and CH₄ by time lag method. As expected, permeability was lowered by any substantial addition of PEG/PEO/PPO regardless the manufacturing process and proportionally to the added amount. About 6 to 7 wt % of PEG/PEO/PPO added to PIM-1 halved permeability compared to PIM-1 membrane prepared under similar conditions. Consequently, selectivity from single gas measurements increased up to values of about 30 for CO₂/N₂ gas pair, a maximum of 18 for CO₂/CH₄ and 3.5 for O₂/N₂.

P/M Processing of Rare Earth Modified High Strength Steels.

DTIC Science & Technology

1980-12-01

AA094 165 TRW INC CLEVELAND OH MATERIALS TECHNOLOGY F 6 P/N PROCESSING OF RARE EARTH MODIFIED HIGH STRENGTH STEELS DEC So A A SHEXM(ER NOOŕT76-C...LEVEL’ (7 PIM PROCESSING OF RARE EARTH MODIFIED HIGH STRENGTH STEELS By A. A. SHEINKER 00 TECHNICAL REPORT Prepared for Office of Naval Research...Processing of Rare Earth Modified High 1 Technical -’ 3t eC"Strength Steels * 1dc4,093Se~ 9PEFRIGOGNZTONAEADADDRESS 10. PROGRAM ELEMENT. PROJECT. TASK

Pim-1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

DTIC Science & Technology

2006-10-01

flavonoids , has been determined. We have also shown that quercetagetin is able to inhibit the activity of the PIM1 kinase in prostate cancer cells...Adventist University, Collegedale, TN 1967-1971, B.A. (biology, chemistry ) Loma Linda University, Loma Linda, CA 1971-1975, M.D

Self-Assessment of Practice Performance: Development of the ABIM Practice Improvement Module (PIM[superscript SM])

ERIC Educational Resources Information Center

Duffy, F. Daniel; Lynn, Lorna A.; Didura, Halyna; Hess, Brian; Caverzagie, Kelly; Grosso, Louis; Lipner, Rebecca A.; Holmboe, Eric S.

2008-01-01

Background: Quality measurement and improvement in practice are requirements for Maintenance of Certification by the American Board of Medical Specialties boards and a component of many pay for performance programs. Objective: To describe the development of the American Board of Internal Medicine (ABIM) Practice Improvement Module (PIM[superscript…

Evolution of a Patient Information Management System in a Local Area Network Environment at Loyola University of Chicago Medical Center

PubMed Central

Price, Ronald N; Chandrasekhar, Arcot J; Tamirisa, Balaji

1990-01-01

The Department of Medicine at Loyola University Medical Center (LUMC) of Chicago has implemented a local area network (LAN) based Patient Information Management System (PIMS) as part of its integrated departmental database management system. PIMS consists of related database applications encompassing demographic information, current medications, problem lists, clinical data, prior events, and on-line procedure results. Integration into the existing departmental database system permits PIMS to capture and manipulate data in other departmental applications. Standardization of clinical data is accomplished through three data tables that verify diagnosis codes, procedures codes and a standardized set of clinical data elements. The modularity of the system, coupled with standardized data formats, allowed the development of a Patient Information Protocol System (PIPS). PIPS, a userdefinable protocol processor, provides physicians with individualized data entry or review screens customized for their specific research protocols or practice habits. Physician feedback indicates that the PIMS/PIPS combination enhances their ability to collect and review specific patient information by filtering large amount of clinical data.

Influence of nitrogen admixture to argon on the ion energy distribution in reactive high power pulsed magnetron sputtering of chromium

NASA Astrophysics Data System (ADS)

Breilmann, W.; Maszl, C.; Hecimovic, A.; von Keudell, A.

2017-04-01

Reactive high power impulse magnetron sputtering (HiPIMS) of metals is of paramount importance for the deposition of various oxides, nitrides and carbides. The addition of a reactive gas such as nitrogen to an argon HiPIMS plasma with a metal target allows the formation of the corresponding metal nitride on the substrate. The addition of a reactive gas introduces new dynamics into the plasma process, such as hysteresis, target poisoning and the rarefaction of two different plasma gases. We investigate the dynamics for the deposition of chromium nitride by a reactive HiPIMS plasma using energy- and time-resolved ion mass spectrometry, fast camera measurements and temporal and spatially resolved optical emission spectroscopy. It is shown that the addition of nitrogen to the argon plasma gas significantly changes the appearance of the localized ionization zones, the so-called spokes, in HiPIMS plasmas. In addition, a very strong modulation of the metal ion flux within each HiPIMS pulse is observed, with the metal ion flux being strongly suppressed and the nitrogen molecular ion flux being strongly enhanced in the high current phase of the pulse. This behavior is explained by a stronger return effect of the sputtered metal ions in the dense plasma above the racetrack. This is best observed in a pure nitrogen plasma, because the ionization zones are mostly confined, implying a very high local plasma density and consequently also an efficient scattering process.

PIM-Check: development of an international prescription-screening checklist designed by a Delphi method for internal medicine patients.

PubMed

Desnoyer, Aude; Blanc, Anne-Laure; Pourcher, Valérie; Besson, Marie; Fonzo-Christe, Caroline; Desmeules, Jules; Perrier, Arnaud; Bonnabry, Pascal; Samer, Caroline; Guignard, Bertrand

2017-07-31

Potentially inappropriate medication (PIM) occurs frequently and is a well-known risk factor for adverse drug events, but its incidence is underestimated in internal medicine. The objective of this study was to develop an electronic prescription-screening checklist to assist residents and young healthcare professionals in PIM detection. Five-step study involving selection of medical domains, literature review and 17 semistructured interviews, a two-round Delphi survey, a forward/back-translation process and an electronic tool development. 22 University and general hospitals from Canada, Belgium, France and Switzerland. 40 physicians and 25 clinical pharmacists were involved in the study.Agreement with the checklist statements and their usefulness for healthcare professional training were evaluated using two 6-point Likert scales (ranging from 0 to 5). Agreement and usefulness ratings were defined as: >65% of the experts giving the statement a rating of 4 or 5, during the first Delphi-round and >75% during the second. 166 statements were generated during the first two steps. Mean agreement and usefulness ratings were 4.32/5 (95% CI 4.28 to 4.36) and 4.11/5 (4.07 to 4.15), respectively, during the first Delphi-round and 4.53/5 (4.51 to 4.56) and 4.36/5 (4.33 to 4.39) during the second (p<0.001). The final checklist includes 160 statements in 17 medical domains and 56 pathologies. An algorithm of approximately 31 000 lines was developed including comorbidities and medications variables to create the electronic tool. PIM-Check is the first electronic prescription-screening checklist designed to detect PIM in internal medicine. It is intended to help young healthcare professionals in their clinical practice to detect PIM, to reduce medication errors and to improve patient safety. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PIM-Check: development of an international prescription-screening checklist designed by a Delphi method for internal medicine patients

PubMed Central

Desnoyer, Aude; Blanc, Anne-Laure; Pourcher, Valérie; Besson, Marie; Fonzo-Christe, Caroline; Desmeules, Jules; Perrier, Arnaud; Bonnabry, Pascal; Samer, Caroline; Guignard, Bertrand

2017-01-01

Objectives Potentially inappropriate medication (PIM) occurs frequently and is a well-known risk factor for adverse drug events, but its incidence is underestimated in internal medicine. The objective of this study was to develop an electronic prescription-screening checklist to assist residents and young healthcare professionals in PIM detection. Design Five-step study involving selection of medical domains, literature review and 17 semistructured interviews, a two-round Delphi survey, a forward/back-translation process and an electronic tool development. Setting 22 University and general hospitals from Canada, Belgium, France and Switzerland. Participants 40 physicians and 25 clinical pharmacists were involved in the study. Agreement with the checklist statements and their usefulness for healthcare professional training were evaluated using two 6-point Likert scales (ranging from 0 to 5). Primary and secondary outcome measures Agreement and usefulness ratings were defined as: >65% of the experts giving the statement a rating of 4 or 5, during the first Delphi-round and >75% during the second. Results 166 statements were generated during the first two steps. Mean agreement and usefulness ratings were 4.32/5 (95% CI 4.28 to 4.36) and 4.11/5 (4.07 to 4.15), respectively, during the first Delphi-round and 4.53/5 (4.51 to 4.56) and 4.36/5 (4.33 to 4.39) during the second (p<0.001). The final checklist includes 160 statements in 17 medical domains and 56 pathologies. An algorithm of approximately 31 000 lines was developed including comorbidities and medications variables to create the electronic tool. Conclusion PIM-Check is the first electronic prescription-screening checklist designed to detect PIM in internal medicine. It is intended to help young healthcare professionals in their clinical practice to detect PIM, to reduce medication errors and to improve patient safety. PMID:28760793

The effect of changing the magnetic field strength on HiPIMS deposition rates

NASA Astrophysics Data System (ADS)

Bradley, J. W.; Mishra, A.; Kelly, P. J.

2015-06-01

The marked difference in behaviour between HiPIMS and conventional dc or pulsed-dc magnetron sputtering discharges with changing magnetic field strengths is demonstrated through measurements of deposition rate. To provide a comparison between techniques the same circular magnetron was operated in the three excitation modes at a fixed average power of 680 W and a pressure of 0.54 Pa in the non-reactive sputtering of titanium. The total magnetic field strength B at the cathode surface in the middle of the racetrack was varied from 195 to 380 G. DC and pulsed-dc discharges show the expected behaviour that deposition rates fall with decreasing B (here by ~25-40%), however the opposite trend is observed in HiPIMS with deposition rates rising by a factor of 2 over the same decrease in B. These observations are understood from the stand point of the different composition and transport processes of the depositing metal flux between the techniques. In HiPIMS, this flux is largely ionic and slow post-ionized sputtered particles are subject to strong back attraction to the target by a retarding plasma potential structure ahead of them. The height of this potential barrier is known to increase with increasing B. From a simple phenomenological model of the sputtered particles fluxes, and using the measured deposition rates from the different techniques as inputs, the combined probabilities of ionization, α, and back attraction, β, of the metal species in HiPIMS has been calculated. There is a clear fall in αβ (from ~0.9 to ~0.7) with decreasing B-field strengths, we argue primarily due to a weakening of electrostatic ion back attraction, so leading to higher deposition rates. The results indicate that careful design of magnetron field strengths should be considered to optimise HiPIMS deposition rates.

The Better Early Childhood Development Program: An Innovative Brazilian Public Policy

ERIC Educational Resources Information Center

Schneider, Alessandra; Ramires, Vera Regina; Paiva, Maria da Graca Gomes; Almeida, Leila

2009-01-01

This paper presents the pioneering experience of the Programa Primeira Infancia Melhor (the Better Early Childhood Development Program), also known as "PIM" that has been developed since 2003 in the State of Rio Grande do Sul, Brazil. PIM's goal is to "provide guidance to families, based on their own culture and experiences, to…

What impact did a Paediatric Early Warning system have on emergency admissions to the paediatric intensive care unit? An observational cohort study.

PubMed

Sefton, G; McGrath, C; Tume, L; Lane, S; Lisboa, P J G; Carrol, E D

2015-04-01

The ideology underpinning Paediatric Early Warning systems (PEWs) is that earlier recognition of deteriorating in-patients would improve clinical outcomes. To explore how the introduction of PEWs at a tertiary children's hospital affects emergency admissions to the Paediatric Intensive Care Unit (PICU) and the impact on service delivery. To compare 'in-house' emergency admissions to PICU with 'external' admissions transferred from District General Hospitals (without PEWs). A before-and-after observational study August 2005-July 2006 (pre), August 2006-July 2007 (post) implementation of PEWs at the tertiary children's hospital. The median Paediatric Index of Mortality (PIM2) reduced; 0.44 vs 0.60 (p<0.001). Fewer admissions required invasive ventilation 62.7% vs 75.2% (p=0.015) for a shorter median duration; four to two days. The median length of PICU stay reduced; five to three days (p=0.002). There was a non-significant reduction in mortality (p=0.47). There was no comparable improvement in outcome seen in external emergency admissions to PICU. A 39% reduction in emergency admission total beds days reduced cancellation of major elective surgical cases and refusal of external PICU referrals. Following introduction of PEWs at a tertiary children's hospital PIM2 was reduced, patients required less PICU interventions and had a shorter length of stay. PICU service delivery improved. Copyright © 2014 Elsevier Ltd. All rights reserved.

Academic Detailing with Provider Audit and Feedback Improve Prescribing Quality for Older Veterans.

PubMed

Vandenberg, Ann E; Echt, Katharina V; Kemp, Lawanda; McGwin, Gerald; Perkins, Molly M; Mirk, Anna K

2018-03-01

Suboptimal prescribing persists as a driver of poor quality care of older veterans and is associated with risk of hospitalization and emergency department visits. We adapted a successful medication management model, Integrated Management and Polypharmacy Review of Vulnerable Elders (IMPROVE), from an urban geriatric specialty clinic to rural community-based clinics that deliver primary care. The goals were to promote prescribing quality and safety for older adults, including reduced prescribing of potentially inappropriate medications (PIMs). We augmented the original model, which involved a pharmacist-led, one-on-one medication review with high-risk older veterans, to provide rural primary care providers (PCPs) and pharmacists with educational outreach through academic detailing and tools to support safe geriatric prescribing practices, as well as individual audit and feedback on prescribing practice and confidential peer benchmarking. Twenty PCPs and 4 pharmacists at 4 rural Georgia community-based outpatient clinics participated. More than 7,000 older veterans were seen in more than 20,000 PCP encounters during the 14-month intervention period. Implementation of the IMPROVE intervention reduced PIM prescribing incidence from 9.6 new medications per 100 encounters during baseline to 8.7 after the intervention (P = .009). IMPROVE reduced PIM prevalence (proportion of encounters involving veterans who were taking at least 1 PIM) from 22.6% to 16.7% (P < .001). These approaches were effective in reducing PIMs prescribed to older veterans in a rural setting and constitute a feasible model for disseminating geriatric best practices to the primary care setting. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

The physical inactivity matrix: lessons from the classification of physical inactivity interventions.

PubMed

Kypri, Kypros; Donaldson, Alex; Johnstone, Elizabeth

2006-05-01

Physical inactivity (PI), a leading modifiable cause of disease and injury, is endemic in industrialised nations. Although considerable research has been undertaken in this field, we lack a system to synthesise the research literature to inform policy and identify research needs. The aims of this study were to (1) develop a system to classify physical inactivity intervention studies, (2) examine the distribution of PI interventions published in the peer-reviewed health literature using the system, and (3) consider implications for future research. We developed the Physical Inactivity Matrix (PIM), with 12 intervention points, created by the intersection of two dimensions: the intervention target (individual, physical environment and social/cultural environment) and the activity focus (transport, work/school, leisure and consumer). A formal search of the health research literature identified 529 eligible studies and each was classified into one of the 12 cells of the PIM. Most studies were categorised as: individual-leisure (68%), individual-work/school (12%) or social/cultural environment-leisure (13%). Only 4% targeted the physical environment. The findings of this initial application of the PIM support the call for greater investment in policies, interventions and research that focus on the relationship between the environment and PI, and transportation in particular. There would be merit in establishing the inter-rater reliability of the PIM and applying it to a wider variety of studies, including those published in the transportation and urban planning literatures. The PIM could be a useful tool for monitoring trends in research directions and funding levels over time and across countries.

Extraction of Gold(III) from Hydrochloric Acid Solutions with a PVC-based Polymer Inclusion Membrane (PIM) Containing Cyphos(®) IL 104.

PubMed

Bonggotgetsakul, Ya Ya Nutchapurida; Cattrall, Robert W; Kolev, Spas D

2015-12-08

Poly(vinyl chloride) (PVC) based polymer inclusion membranes (PIMs), with different concentrations of Cyphos® IL 104 as the membrane extractant/carrier, were studied for their ability to extract Au(III) from hydrochloric acid solutions. Some of the PIMs also contained one of the following plasticizers or modifiers: 2-nitrophenyloctyl ether, dioctylphthalate, 1-dodecanol, 1-tetradecanol, or tri(2-ethylhexyl) phosphate. The best performance, in terms of extraction rate and amount of Au(III) extracted, was exhibited by a PIM consisting of 25 wt% Cyphos(®) IL 104, 5 wt% 1-dodecanol, and 70 wt% PVC. An almost complete back-extraction of the Au(III) extracted from this membrane was achieved by using a 0.10 mol L(-1) Na₂SO₃ receiver solution at pH 8. The stoichiometry of the extracted Au(III)/Cyphos® IL 104 adduct was determined as [P]⁺ [AuCl₄](-) H⁺ [PO₂](-) where [P]⁺ and [PO₂](-) represent trihexyl(tetradecyl) phosphonium and bis(2,4,4-trimethylpentyl) phosphinate ions, respectively. Back-extraction of Au(III) is suggested to occur by reduction of Au(III) to Au(I), with the formation of the species [Au(SO₃)₂](3-) in the aqueous receiver solution. Loss of 1-dodecanol from the newly developed PIM to the aqueous solutions in contact with it was observed, which indicated that this membrane was suitable for single use in the efficient recovery of Au(III) from hydrochloric acid solutions of electronic scrap or recycled jewelry.

On Effective Radiative Forcing of Partial Internally and Externally Mixed Aerosols and Their Effects on Global Climate

NASA Astrophysics Data System (ADS)

Zhou, Chen; Zhang, Hua; Zhao, Shuyun; Li, Jiangnan

2018-01-01

The total effective radiative forcing (ERF) due to partial internally mixed (PIM) and externally mixed (EM) anthropogenic aerosols, as well as their climatic effects since the year of 1850, was evaluated and compared using the aerosol-climate online coupled model of BCC_AGCM2.0_CUACE/Aero. The influences of internal mixing (IM) on aerosol hygroscopicity parameter, optical properties, and concentration were considered. Generally, IM could markedly weaken the negative ERF and cooling effects of anthropogenic aerosols. The global annual mean ERF of EM anthropogenic aerosols from 1850 to 2010 was -1.87 W m-2, of which the aerosol-radiation interactive ERF (ERFari) and aerosol-cloud interactive ERF (ERFaci) were -0.49 and -1.38 W m-2, respectively. The global annual mean ERF due to PIM anthropogenic aerosols from 1850 to 2010 was -1.23 W m-2, with ERFari and ERFaci of -0.23 and -1.01 W m-2, respectively. The global annual mean surface temperature and water evaporation and precipitation were reduced by 1.74 K and 0.14 mm d-1 for EM scheme and 1.28 K and 0.11 mm d-1 for PIM scheme, respectively. However, the relative humidity near the surface was slightly increased for both mixing cases. The Intertropical Convergence Zone was southwardly shifted for both EM and PIM cases but was less southwardly shifted in PIM scheme due to the less reduction in atmospheric temperature in the midlatitude and low latitude of the Northern Hemisphere.

Characterization of high power impulse magnetron sputtering discharges

NASA Astrophysics Data System (ADS)

Hala, Matej

Paper I: In the first paper, we present a new approach in the characterization of the high power pulsed magnetron sputtering (HiPIMS) discharge evolution—time- and species-resolved plasma imaging—employing a set of band-pass optical interference filters suitable for the isolation of the emission originating from different species populating the plasma. We demonstrate that the introduction of such filters can be used to distinguish different phases of the discharge, and to visualize numerous plasma effects including background gas excitations during the discharge ignition, gas shock waves, and expansion of metal-rich plasmas. In particular, the application of this technique is shown on the diagnostics of the 200 µs long non-reactive HiPIMS discharges using a Cr target. Paper II: In order to gain further information about the dynamics of reactive HiPIMS discharges, both fast plasma imaging and time- and space-resolved optical emission spectroscopy (OES) are used for a systematic investigation of the 200 µs long HiPIMS pulses operated in Ar, N2 and N 2/Ar mixtures and at various pressures. It is observed that the dense metal plasma created next to the target propagates in the reactor at a speed ranging from 0.7 to 3.5 km s-1, depending on the working gas composition and the pressure. In fact, it increases with higher N 2 concentration and with lower pressure. The visible form of the propagating plasma wave changes from a hemispherical shape in Ar to a drop-like shape extending far from the target with increasing N2 concentration, owing to the significant emission from molecular N2. Interestingly, the evidence of the target self-sputtering is found for all investigated conditions, including pure N2 atmosphere. Paper III: Here, we report on the time- and species-resolved plasma imaging analysis of the dynamics of the 200 µs long HiPIMS discharges above a Cr target ignited in pure O2. It is shown that the discharge emission is dominated solely by neutral and ionized oxygen, since the monitored discharge is operated above a fully poisoned (oxidized) target from which only a minimum of Cr is sputtered. No signs of self-sputtering have been detected, in contrast to the discharges in Ar, N2 and N2/Ar mixtures previously investigated. Paper IV: In the fourth paper, we study different power management approaches in HiPIMS and MPPMS and their effects on the pulsed discharge evolution, plasma composition, and metal ionization estimated by OES. It is shown that HiPIMS is the only technique that enables the discharge operation in self-sputtering mode within the investigated range of applied powers, resulting in a significantly higher ionization of the sputtered metal than that reached with MPPMS. In contrast to HiPIMS, MPPMS provides a higher versatility in adjusting the pulse shape and pulse length. This feature can be particularly beneficial, for instance, in the discharge ignition. Nb coatings prepared by HiPIMS and MPPMS have very similar deposition rates that are lower than in DCMS. All films prepared at p = 1Pa possess a dense columnar structure. Coatings deposited by the two high power pulsed discharges exhibit higher compressive stress and larger out-of-plane lattice spacing than those prepared by DC sputtering under comparable conditions. At higher pressure, p = 2Pa, DCMS-grown films show a tensile stress due to a porous microstructure, while films prepared by HiPIMS and MPPMS are dense and in compression, most probably due to the substantial ion bombardment. Paper V: In the last paper, we analyze the behavior of the HiPIMS, MPPMS and DCMS discharges in reactive O2/Ar gas mixtures and evaluate the characteristics of the fabricated NbOx films. We demonstrate that the surface metal oxides can be effectively sputter-eroded from the target during both HiPIMS and MPPMS pulses, and that sputtering from a partially oxide-free target is possible even at high oxygen concentrations. This results in a hysteresisfree deposition process which allows one to prepare optically transparent b2O5 coatings at a high growth rate without the need of feedback control commonly used in reactive DCMS. Nb2O 5 coatings prepared by both reactive high power pulsed discharges exhibited a high index of refraction, a low extinction coefficient, a near-zero internal stress, and high hardness and Young's modulus. The HiPIMS-deposited coatings showed the highest deposition rate and the highest index of refraction. The latter observation was related to the higher film density. In comparison, MPPMS exhibited the highest power-normalized deposition rate among the three investigated deposition techniques, possibly due to the longer period that is available for the gradual target cleaning. (Abstract shortened by UMI.).

Photodynamic immune modulation (PIM)

NASA Astrophysics Data System (ADS)

North, John R.; Hunt, David W. C.; Simkin, Guillermo O.; Ratkay, Leslie G.; Chan, Agnes H.; Lui, Harvey; Levy, Julia G.

1999-09-01

Photodynamic Therapy (PDT) is accepted for treatment of superficial and lumen-occluding tumors in regions accessible to activating light and is now known to be effective in closure of choroidal neovasculature in Age Related Macular Degeneration. PDT utilizes light absorbing drugs (photosensitizers) that generate the localized formation of reactive oxygen species after light exposure. In a number of systems, PDT has immunomodulatory effects; Photodynamic Immune Modulation (PIM). Using low- intensity photodynamic regimens applied over a large body surface area, progression of mouse autoimmune disease could be inhibited. Further, this treatment strongly inhibited the immunologically- medicated contact hypersensitivity response to topically applied chemical haptens. Immune modulation appears to result from selective targeting of activated T lymphocytes and reduction in immunostimulation by antigen presenting cells. Psoriasis, an immune-mediated skin condition, exhibits heightened epidermal cell proliferation, epidermal layer thickening and plaque formation at different body sites. In a recent clinical trial, approximately one-third of patients with psoriasis and arthritis symptoms (psoriatic arthritis) displayed a significant clinical improvement in several psoriasis-related parameters after four weekly whole-body PIM treatments with verteporfin. The safety profile was favorable. The capacity of PIM to influence other human immune disorders including rheumatoid arthritis is under extensive evaluation.

Can foreign proteins imported into yeast mitochondria interfere with PIM1p protease and/or chaperone function?

PubMed

Saveliev, A S; Kovaleva, I E; Novikova, L A; Isaeva, L V; Luzikov, V N

1999-03-15

When studying the fate of mammalian apocytochrome P450scc (apo-P450scc) imported in small amounts into isolated yeast mitochondria, we found that it undergoes degradation, this process being retarded if recipient mitochondria are preloaded in vivo (to about 0.2% of total organelle protein) with a fusion protein composed of mammalian adrenodoxin reductase and adrenodoxin (AdR-Ad); in parallel we observed aggregation of apo-P450scc. These effects suggest some overload of Pim1p protease and/or mtHsp70 system by AdR-Ad, as both of them are involved in the degradation of apo-P450scc (see Savel'ev et al. J. Biol. Chem. 273, 20596-20602, 1998). However, under the same conditions AdR-Ad was not able to impede the import of proteins into mitochondria and the development of the mitochondrial respiratory machinery in yeast, the processes requiring the mtHsp70 system and Pim1p, respectively. These data imply that chaperones and Pim1p protease prefer their natural targets in mitochondria to imported foreign proteins. Copyright 1999 Academic Press.

Simultaneous AuIII Extraction and In Situ Formation of Polymeric Membrane-Supported Au Nanoparticles: A Sustainable Process with Application in Catalysis.

PubMed

Mora-Tamez, Lucía; Esquivel-Peña, Vicente; Ocampo, Ana L; Rodríguez de San Miguel, Eduardo; Grande, Daniel; de Gyves, Josefina

2017-04-10

A polymeric membrane-supported catalyst with immobilized gold nanoparticles (AuNPs) was prepared through the extraction and in situ reduction of Au III salts in a one-step strategy. Polymeric inclusion membranes (PIMs) and polymeric nanoporous membranes (PNMs) were tested as different membrane-support systems. Transport experiments indicated that PIMs composed of cellulose triacetate, 2-nitrophenyloctyl ether, and an aliphatic tertiary amine (Adogen 364 or Alamine 336) were the most efficient supports for Au III extraction. The simultaneous extraction and reduction processes were proven to be the result of a synergic phenomenon in which all the membrane components were involved. Scanning electron microscopy characterization of cross-sectional samples suggested a distribution of AuNPs throughout the membrane. Transmission electron microscopy characterization of the AuNPs indicated average particle sizes of 36.7 and 2.9 nm for the PIMs and PNMs, respectively. AuNPs supported on PIMs allowed for >95.4 % reduction of a 0.05 mmol L -1 4-nitrophenol aqueous solution with 10 mmol L -1 NaBH 4 solution within 25 min. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using OPC and HL7 Standards to Incorporate an Industrial Big Data Historian in a Health IT Environment.

PubMed

Cruz, Márcio Freire; Cavalcante, Carlos Arthur Mattos Teixeira; Sá Barretto, Sérgio Torres

2018-05-30

Health Level Seven (HL7) is one of the standards most used to centralize data from different vital sign monitoring systems. This solution significantly limits the data available for historical analysis, because it typically uses databases that are not effective in storing large volumes of data. In industry, a specific Big Data Historian, known as a Process Information Management System (PIMS), solves this problem. This work proposes the same solution to overcome the restriction on storing vital sign data. The PIMS needs a compatible communication standard to allow storing, and the one most commonly used is the OLE for Process Control (OPC). This paper presents a HL7-OPC Server that permits communication between vital sign monitoring systems with PIMS, thus allowing the storage of long historical series of vital signs. In addition, it carries out a review about local and cloud-based Big Medical Data researches, followed by an analysis of the PIMS in a Health IT Environment. Then it shows the architecture of HL7 and OPC Standards. Finally, it shows the HL7-OPC Server and a sequence of tests that proved its full operation and performance.

Protein Profiling Identifies mTOR Pathway Modulation and Cytostatic Effects of Pim Kinase Inhibitor, AZD1208, in Acute Myeloid Leukemia

PubMed Central

Chen, Lisa S.; Yang, Ji-Yeon; Liang, Han; Cortes, Jorge E.; Gandhi, Varsha

2017-01-01

Pim kinases phosphorylate and regulate a number of key AML cell survival proteins, and Pim inhibitors have recently entered clinical trial for hematological malignancies. AZD1208 is a small molecule pan-Pim kinase inhibitor and AZD1208 treatment resulted in growth inhibition and cell size reduction in AML cell lines including FLT3-WT (OCI-AML-3, KG-1a, MOLM-16) and FLT3-ITD mutated (MOLM-13, MV-4-11). There was limited apoptosis induction (<10% increase) in the AML cell lines evaluated with up to 3 μM AZD1208 for 24h, suggesting that growth inhibition is not through apoptosis induction. Using reverse phase protein array (RPPA) and immunoblot analysis, we identified that AZD1208 resulted in suppression of mTOR signaling, including inhibition of protein phosphorylation of mTOR(Ser2448), p70S6K(Thr389), S6(Ser235/236) and 4E-BP1(Ser65). Consistent with mTOR inhibition, there was also a reduction in protein synthesis that correlated with cell size reduction and growth inhibition with AZD1208; our study provide insights into the mechanism of AZD1208. PMID:27054578

M109 Family of Vehicles, Paladin Integrated Management (PIM): Operational Assessment of the Initial Operational Test and Evaluation (IOT and E)

DTIC Science & Technology

2017-01-01

procedures and Army doctrine. During pre -IOT&E training and developmental testing , the combat developer discovered that when projectiles were fired using...Director, Operational Test and Evaluation M109 Family of Vehicles, Paladin Integrated Management (PIM) Operational Assessment of the...Initial Operational Test and Evaluation October 2011 January 2017 J. Michael Gilmore Director

The use of a polymer inclusion membrane in a paper-based sensor for the selective determination of Cu(II).

PubMed

Jayawardane, B Manori; Coo, Lilibeth dlC; Cattrall, Robert W; Kolev, Spas D

2013-11-25

A disposable paper-based sensor (PBS) is described for the determination of Cu(II) in natural and waste waters at approximately 2 cents per measurement. The device makes use of a polymer inclusion membrane (PIM) to provide the selectivity for Cu(II). The PIM consists of 40 wt% di(2-ethlyhexyl) phosphoric acid (D2EHPA) as the carrier, 10 wt% dioctyl phthalate (DOP) as a plasticizer, 49.5 wt% poly(vinyl chloride) (PVC) as the base polymer and 0.5 wt% (mm(-1)) 1-(2'-pyridylazo)-2-naphthol (PAN) as the colourimetric reagent. High selectivity under mildly acidic conditions (HCl, pH 2.0) is achieved for Cu(II) in the presence of frequently encountered metal ions in natural and waste waters such as Fe(III), Al(III), Zn(II), Cd(II), Pb(II), Ca(II), Mg(II), and Ni(II). The laminated PBS consists of a PIM sensing disc (2mm in diameter) attached to the centre of a circular hydrophilic zone (7 mm in diameter) pretreated with 0.01 M HCl. This hydrophilic zone separates the sample port (a circular hole in the plastic cover) from the PIM sensing disc. After introducing 19.2 μL of a sample/standard solution to the sample port, Cu(II) diffuses across the hydrophilic zone and is extracted into the PIM disc as the Cu(II)-D2EHPA complex which subsequently reacts with PAN to produce the red-purple coloured Cu(II)-PAN complex. The colour intensity of the PIM disc is measured 15 min after sample/standard introduction by scanning using a flatbed scanner. Under optimal conditions the device is characterized by a limit of detection (LOD) and limit of quantitation (LOQ) of 0.06 and 0.21 mg L(-1) Cu(II), respectively, with two linear ranges together covering the Cu(II) concentration range from 0.1 to 30.0 mg L(-1). The PBS was successfully applied to the determination of Cu(II) in hot tap water and mine tailings water. Copyright © 2013 Elsevier B.V. All rights reserved.

Concurrent Inhibition of Pim and FLT3 Kinases Enhances Apoptosis of FLT3-ITD Acute Myeloid Leukemia Cells through Increased Mcl-1 Proteasomal Degradation.

PubMed

Kapoor, Shivani; Natarajan, Karthika; Baldwin, Patrick R; Doshi, Kshama A; Lapidus, Rena G; Mathias, Trevor J; Scarpa, Mario; Trotta, Rossana; Davila, Eduardo; Kraus, Manfred; Huszar, Dennis; Tron, Adriana E; Perrotti, Danilo; Baer, Maria R

2018-01-01

Purpose: fms -like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is present in 30% of acute myeloid leukemia (AML), and these patients have short disease-free survival. FLT3 inhibitors have limited and transient clinical activity, and concurrent treatment with inhibitors of parallel or downstream signaling may improve responses. The oncogenic serine/threonine kinase Pim-1 is upregulated downstream of FLT3-ITD and also promotes its signaling in a positive feedback loop, suggesting benefit of combined Pim and FLT3 inhibition. Experimental Design: Combinations of clinically active Pim and FLT3 inhibitors were studied in vitro and in vivo Results: Concurrent treatment with the pan-Pim inhibitor AZD1208 and FLT3 inhibitors at clinically applicable concentrations abrogated in vitro growth of FLT3-ITD, but not wild-type FLT3 (FLT3-WT), cell lines. AZD1208 cotreatment increased FLT3 inhibitor-induced apoptosis of FLT3-ITD, but not FLT3-WT, cells measured by sub-G 1 fraction, annexin V labeling, mitochondrial membrane potential, and PARP and caspase-3 cleavage. Concurrent treatment with AZD1208 and the FLT3 inhibitor quizartinib decreased growth of MV4-11 cells, with FLT3-ITD, in mouse xenografts, and prolonged survival, enhanced apoptosis of FLT3-ITD primary AML blasts, but not FLT3-WT blasts or remission marrow cells, and decreased FLT3-ITD AML blast colony formation. Mechanistically, AZD1208 and quizartinib cotreatment decreased expression of the antiapoptotic protein Mcl-1. Decrease in Mcl-1 protein expression was abrogated by treatment with the proteasome inhibitor MG132, and was preceded by downregulation of the Mcl-1 deubiquitinase USP9X, a novel mechanism of Mcl-1 regulation in AML. Conclusions: The data support clinical testing of Pim and FLT3 inhibitor combination therapy for FLT3-ITD AML. Clin Cancer Res; 24(1); 234-47. ©2017 AACR . ©2017 American Association for Cancer Research.

Apoplastic effectors secreted by two unrelated eukaryotic plant pathogens target the tomato defense protease Rcr3.

PubMed

Song, Jing; Win, Joe; Tian, Miaoying; Schornack, Sebastian; Kaschani, Farnusch; Ilyas, Muhammad; van der Hoorn, Renier A L; Kamoun, Sophien

2009-02-03

Current models of plant-pathogen interactions stipulate that pathogens secrete effector proteins that disable plant defense components known as virulence targets. Occasionally, the perturbations caused by these effectors trigger innate immunity via plant disease resistance proteins as described by the "guard hypothesis." This model is nicely illustrated by the interaction between the fungal plant pathogen Cladosporium fulvum and tomato. C. fulvum secretes a protease inhibitor Avr2 that targets the tomato cysteine protease Rcr3(pim). In plants that carry the resistance protein Cf2, Rcr3(pim) is required for resistance to C. fulvum strains expressing Avr2, thus fulfilling one of the predictions of the guard hypothesis. Another prediction of the guard hypothesis has not yet been tested. Considering that virulence targets are important components of defense, different effectors from unrelated pathogens are expected to evolve to disable the same host target. In this study we confirm this prediction using a different pathogen of tomato, the oomycete Phytophthora infestans that is distantly related to fungi such as C. fulvum. This pathogen secretes an array of protease inhibitors including EPIC1 and EPIC2B that inhibit tomato cysteine proteases. Here we show that, similar to Avr2, EPIC1 and EPIC2B bind and inhibit Rcr3(pim). However, unlike Avr2, EPIC1 and EPIC2B do not trigger hypersensitive cell death or defenses on Cf-2/Rcr3(pim) tomato. We also found that the rcr3-3 mutant of tomato that carries a premature stop codon in the Rcr3 gene exhibits enhanced susceptibility to P. infestans, suggesting a role for Rcr3(pim) in defense. In conclusion, our findings fulfill a key prediction of the guard hypothesis and suggest that the effectors Avr2, EPIC1, and EPIC2B secreted by two unrelated pathogens of tomato target the same defense protease Rcr3(pim). In contrast to C. fulvum, P. infestans appears to have evolved stealthy effectors that carry inhibitory activity without triggering plant innate immunity.

The lipoprotein LpqW is essential for the mannosylation of periplasmic glycolipids in Corynebacteria.

PubMed

Rainczuk, Arek K; Yamaryo-Botte, Yoshiki; Brammananth, Rajini; Stinear, Timothy P; Seemann, Torsten; Coppel, Ross L; McConville, Malcolm J; Crellin, Paul K

2012-12-14

Phosphatidylinositol mannosides (PIM), lipomannan (LM), and lipoarabinomannan (LAM) are essential components of the cell wall and plasma membrane of mycobacteria, including the human pathogen Mycobacterium tuberculosis, as well as the related Corynebacterineae. We have previously shown that the lipoprotein, LpqW, regulates PIM and LM/LAM biosynthesis in mycobacteria. Here, we provide direct evidence that LpqW regulates the activity of key mannosyltransferases in the periplasmic leaflet of the cell membrane. Inactivation of the Corynebacterium glutamicum lpqW ortholog, NCgl1054, resulted in a slow growth phenotype and a global defect in lipoglycan biosynthesis. The NCgl1054 mutant lacked LAMs and was defective in the elongation of the major PIM species, AcPIM2, as well as a second glycolipid, termed Gl-X (mannose-α1-4-glucuronic acid-α1-diacylglycerol), which function as membrane anchors for LM-A and LM-B, respectively. Elongation of AcPIM2 and Gl-X was found to be dependent on expression of polyprenol phosphomannose (ppMan) synthase. However, the ΔNCgl1054 mutant synthesized normal levels of ppMan, indicating that LpqW is not required for synthesis of this donor. A spontaneous suppressor strain was isolated in which lipoglycan synthesis in the ΔNCgl1054 mutant was partially restored. Genome-wide sequencing indicated that a single amino acid substitution within the ppMan-dependent mannosyltransferase MptB could bypass the need for LpqW. Further evidence of an interaction is provided by the observation that MptB activity in cell-free extracts was significantly reduced in the absence of LpqW. Collectively, our results suggest that LpqW may directly activate MptB, highlighting the role of lipoproteins in regulating key cell wall biosynthetic pathways in these bacteria.

Polymorphism of alpha-1-antitrypsin in hematological malignancies

PubMed Central

2009-01-01

Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (χ2 = 4.42, d.f.11, p = 0.96 and χ2 = 4.71, d.f.11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant. PMID:21637443

Computerised interventions designed to reduce potentially inappropriate prescribing in hospitalised older adults: a systematic review and meta-analysis.

PubMed

Dalton, Kieran; O'Brien, Gary; O'Mahony, Denis; Byrne, Stephen

2018-06-08

computerised interventions have been suggested as an effective strategy to reduce potentially inappropriate prescribing (PIP) for hospitalised older adults. This systematic review and meta-analysis examined the evidence for efficacy of computerised interventions designed to reduce PIP in this patient group. an electronic literature search was conducted using eight databases up to October 2017. Included studies were controlled trials of computerised interventions aiming to reduce PIP in hospitalised older adults (≥65 years). Risk of bias was assessed using Cochrane's Effective Practice and Organisation of Care criteria. of 653 records identified, eight studies were included-two randomised controlled trials, two interrupted time series analysis studies and four controlled before-after studies. Included studies were mostly at a low risk of bias. Overall, seven studies showed either a statistically significant reduction in the proportion of patients prescribed a potentially inappropriate medicine (PIM) (absolute risk reduction {ARR} 1.3-30.1%), or in PIMs ordered (ARR 2-5.9%). However, there is insufficient evidence thus far to suggest that these interventions can routinely improve patient-related outcomes. It was only possible to include three studies in the meta-analysis-which demonstrated that intervention patients were less likely to be prescribed a PIM (odds ratio 0.6; 95% CI 0.38, 0.93). No computerised intervention targeting potential prescribing omissions (PPOs) was identified. this systematic review concludes that computerised interventions are capable of statistically significantly reducing PIMs in hospitalised older adults. Future interventions should strive to target both PIMs and PPOs, ideally demonstrating both cost-effectiveness data and clinically significant improvements in patient-related outcomes.

Potentially inappropriate medication in the elderly in Germany: an economic appraisal of the PRISCUS list.

PubMed

Pohl-Dernick, Katharina; Meier, Florian; Maas, Renke; Schöffski, Oliver; Emmert, Martin

2016-04-01

Several lists of potentially inappropriate medication (PIM) for elderly patients have been developed worldwide in recent years. Those lists intend to reduce prescriptions of drugs that carry an unnecessarily high risk of adverse drug events in elderly patients. In 2010, an expert panel published the PRISCUS list for the German drug market. This study calculates the amount of drug reimbursement for PIM in Germany and potential cost effects from the perspective of statutory health insurance when these are replaced by the substitutes recommended by the PRISCUS list. Register-based data for the 30 top-selling drugs on the PRISCUS list in 2009 for patients greater than or equal to 65 years of age were provided by the Scientific Institute of the German Local Health Care Fund. We calculated the percentage of sales and defined daily doses for patients greater than or equal to 65 years of age compared with the total statutory health insurance population. Reimbursement costs for the recommended substitutions were estimated by considering different scenarios. In 2009, drug reimbursement for the 30 top-selling PIM prescribed to patients greater than or equal to 65 years of age were calculated to be €305.7 million. Prescribing the recommended substitution medication instead of PIM would lead to an increased total reimbursement cost for the German health care system ranging between from €325.9 million to €810.0 million. The results show that the substitution of PIM by medication deemed to be more appropriate for the elderly comes along with additional costs. Consequently, there is no short-term incentive for doing so from a payer perspective. Future studies have to consider the long-term effects and other sectors.

Biological Effects of the Pim Kinase Inhibitor, SGI-1776, in Multiple Myeloma

PubMed Central

Cervantes-Gomez, Fabiola; Chen, Lisa S.; Orlowski, Robert Z.; Gandhi, Varsha

2013-01-01

Pim kinases are constitutively active serine/threonine/tyrosine kinases that are overexpressed in hematological malignancies such as multiple myeloma. Pim kinase substrates are involved in transcription, protein translation, cell proliferation, and apoptosis. SGI-1776 is a potent Pim kinase inhibitor that has proven to be cytotoxic to leukemia and lymphoma cells. Based on this background, we hypothesized that SGI-1776 treatment would result in myeloma cytotoxicity. To test this, myeloma cell lines and primary CD138+ cells from myeloma patients were treated with SGI-1776 in a dose- and time-dependent manner and effect on cell death and proliferation, induction of autophagy, as wells as changes in cell cycle profile were measured. SGI-1776 treatment resulted in limited apoptosis in cell lines (mean 30%) and CD138+ cells (<10%) as assessed by Annexin-V/PI. Limited effect was observed in cell cycle profile or growth in cell lines. However, DNA synthesis was decreased by 70% at 3 μM (all time points) in U266 though this was not observed in MM.1S. In accordance, immunoblot analyses revealed no change in transcription (c-Myc and H3), or apoptotic (Bad) proteins that are substrates of Pim kinases. In contrast, autophagy, as assessed by acridine orange staining, was induced with SGI-1776 treatment in both cell lines (U266 25-70%; MM.1S 8-52%) and CD138+ cells (19-21%). Immunoblot analyses of autophagy LC3b marker and translation initiation proteins (phospho p70S6K and 4E-BP1) corroborated autophagy induction. These data indicate that SGI-1776 treatment in myeloma cell lines and CD138+ myeloma cells elicits its deleterious effects through inhibition of translation and induction of autophagy. PMID:23988451

Biological effects of the Pim kinase inhibitor, SGI-1776, in multiple myeloma.

PubMed

Cervantes-Gomez, Fabiola; Chen, Lisa S; Orlowski, Robert Z; Gandhi, Varsha

2013-09-01

Pim kinases are constitutively active serine/threonine/tyrosine kinases that are overexpressed in hematological malignancies such as multiple myeloma. Pim kinase substrates are involved in transcription, protein translation, cell proliferation, and apoptosis. SGI-1776 is a potent Pim kinase inhibitor that has proven to be cytotoxic to leukemia and lymphoma cells. Based on this background, we hypothesized that SGI-1776 treatment would result in myeloma cytotoxicity. To test this, myeloma cell lines and primary CD138(+) cells from myeloma patients were treated with SGI-1776 in a dose- and time-dependent manner, and effect on cell death and proliferation, induction of autophagy, and changes in cell cycle profile were measured. SGI-1776 treatment resulted in limited apoptosis in cell lines (mean 30%) and CD138(+) cells (< 10%) assessed using Annexin-V/propidium iodide. Limited effect was observed in cell cycle profile or growth in cell lines. However, DNA synthesis was decreased by 70% at 3 μM (all time points) in U266 though this was not observed in MM.1S. In accordance, immunoblot analyses revealed no change in transcription (c-Myc and H3), or apoptotic (Bad) proteins that are substrates of Pim kinases. In contrast, autophagy, assessed using acridine orange staining, was induced with SGI-1776 treatment in both cell lines (U266, 25%-70%; MM.1S, 8%-52%) and CD138(+) cells (19%-21%). Immunoblot analyses of the autophagy LC3b marker and translation initiation proteins (phospho-p70S6K and 4E-BP1) corroborated autophagy induction. These data indicate that SGI-1776 treatment in myeloma cell lines and CD138(+) myeloma cells elicits its deleterious effects through inhibition of translation and induction of autophagy. Copyright © 2013 Elsevier Inc. All rights reserved.

Novel Therapeutic Approaches Toward Treating Prostate Cancer

DTIC Science & Technology

2013-05-01

Kinases, Prostate Cancer, AKT inhibition, Mouse, Prostate Stem Cells 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...Bearss 0, Wierda WG, Gandhi V (2009) Pim kinase inhibitor, 5GI-1776, induces apoptosis in CLL lymphocytes. Blood 114:4150--4157. 27. Grey R, et aL...PIM1 expression predict outcome in mantle cell lymphoma treated with high dose therapy, stem eel! transplantation and rituximab: a Cancer and Leukemia

Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...SUBTITLE 5a. CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM...blocked by the addition of Pim inhibitors. These results suggest that the Pim protein kinase can regulate stromal cell biology to modulate epithelial

Is there any relationship between proinflammatory mediator levels in disc material and myelopathy with cervical disc herniation and spondylosis? A non-randomized, prospective clinical study

PubMed Central

Asir, Alparslan; Cetinkal, Ahmet; Gedik, Nursal; Kutlay, Ahmet Murat; Çolak, Ahmet; Kurtar, Sedat; Simsek, Hakan

2007-01-01

The proinflammatory mediator (PIM) levels were assessed in surgically removed samples of herniated cervical intervertebral discs. The objective of this study was to investigate if there is a correlation between the levels of PIMs in disc material and myelopathy associated with cervical intervertebral disc herniation and spondylosis. The role of proinflammatory mediators in the degeneration of intervertebral disc and the inflammatory effects of disc herniations on radicular pain has been previously published. However, the possible relationship between PIMs and myelopathy related to cervical disc herniation and spondylosis has not been investigated before. Thirty-two patients undergoing surgery for cervical disc herniation and spondylosis were investigated. Surgically obtained disc materials, stored at 70°C, were classified into two groups: cervical disc herniation alone or with myelopathy. Biochemical preparation and solid phase enzyme amplified sensitivity immunoassay (ELISIA) analysis of the samples were performed to assess the concentration of mediators in the samples. Very similar values of interleukin-6 were found in both groups whereas the concentrations of mediators were significantly higher in myelopathy group. This study has demonstrated that PIMs are involved in cervical intervertebral disc degeneration with higher concentrations in the samples associated with myelopathy. PMID:17476536

Polymer ultrapermeability from the inefficient packing of 2D chains

NASA Astrophysics Data System (ADS)

Rose, Ian; Bezzu, C. Grazia; Carta, Mariolino; Comesaña-Gándara, Bibiana; Lasseuguette, Elsa; Ferrari, M. Chiara; Bernardo, Paola; Clarizia, Gabriele; Fuoco, Alessio; Jansen, Johannes C.; Hart, Kyle E.; Liyana-Arachchi, Thilanga P.; Colina, Coray M.; McKeown, Neil B.

2017-09-01

The promise of ultrapermeable polymers, such as poly(trimethylsilylpropyne) (PTMSP), for reducing the size and increasing the efficiency of membranes for gas separations remains unfulfilled due to their poor selectivity. We report an ultrapermeable polymer of intrinsic microporosity (PIM-TMN-Trip) that is substantially more selective than PTMSP. From molecular simulations and experimental measurement we find that the inefficient packing of the two-dimensional (2D) chains of PIM-TMN-Trip generates a high concentration of both small (<0.7 nm) and large (0.7-1.0 nm) micropores, the former enhancing selectivity and the latter permeability. Gas permeability data for PIM-TMN-Trip surpass the 2008 Robeson upper bounds for O2/N2, H2/N2, CO2/N2, H2/CH4 and CO2/CH4, with the potential for biogas purification and carbon capture demonstrated for relevant gas mixtures. Comparisons between PIM-TMN-Trip and structurally similar polymers with three-dimensional (3D) contorted chains confirm that its additional intrinsic microporosity is generated from the awkward packing of its 2D polymer chains in a 3D amorphous solid. This strategy of shape-directed packing of chains of microporous polymers may be applied to other rigid polymers for gas separations.

Device research task (processing and high-efficiency solar cells)

NASA Technical Reports Server (NTRS)

1986-01-01

This task has been expanded since the last 25th Project Integration Meeting (PIM) to include process research in addition to device research. The objective of this task is to assist the Flat-plate Solar Array (FSA) Project in meeting its near- and long-term goals by identifying and implementing research in the areas of device physics, device structures, measurement techniques, material-device interactions, and cell processing. The research efforts of this task are described and reflect the deversity of device research being conducted. All of the contracts being reported are either completed or near completion and culminate the device research efforts of the FSA Project. Optimazation methods and silicon solar cell numerical models, carrier transport and recombination parameters in heavily doped silicon, development and analysis of silicon solar cells of near 20% efficiency, and SiN sub x passivation of silicon surfaces are discussed.

Magnetic field effect on spoke behaviour

NASA Astrophysics Data System (ADS)

Hnilica, Jaroslav; Slapanska, Marta; Klein, Peter; Vasina, Petr

2016-09-01

The investigations of the non-reactive high power impulse magnetron sputtering (HiPIMS) discharge using high-speed camera imaging, optical emission spectroscopy and electrical probes showed that plasma is not homogeneously distributed over the target surface, but it is concentrated in regions of higher local plasma density called spokes rotating above the erosion racetrack. Magnetic field effect on spoke behaviour was studied by high-speed camera imaging in HiPIMS discharge using 3 inch titanium target. An employed camera enabled us to record two successive images in the same pulse with time delay of 3 μs between them, which allowed us to determine the number of spokes, spoke rotation velocity and spoke rotation frequency. The experimental conditions covered pressure range from 0.15 to 5 Pa, discharge current up to 350 A and magnetic fields of 37, 72 and 91 mT. Increase of the magnetic field influenced the number of spokes observed at the same pressure and at the same discharge current. Moreover, the investigation revealed different characteristic spoke shapes depending on the magnetic field strength - both diffusive and triangular shapes were observed for the same target material. The spoke rotation velocity was independent on the magnetic field strength. This research has been financially supported by the Czech Science Foundation in frame of the project 15-00863S.

Design And Commissioning Status Of New Cylindrical HiPIMS Nb Coating System for SRF Cavities

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

Phillips, H. Lawrence; Macha, Kurt M.; Valente-Feliciano, Anne-Marie

2014-02-01

For the past 19 years Jefferson Lab has sustained a program studying niobium films deposited on small samples in order to develop an understanding of the correlation between deposition parameters, film micro-structure, and RF performance. A new cavity deposition system employing a cylindrical cathode using the HiPIMS technique has been developed to apply this work to cylindrical cavities. The status of this system will be presented.

Powder Injection Molding (PIM) for Low Cost Manufacturing of Intricate Parts to Net-Shape

DTIC Science & Technology

2006-05-01

tungsten - or molybdenum-pseudoalloys, which can be net-shape manufactured only by PIM because of the tight dimension tolerances needed for the final...materials. Rhenium metal, for instance, which costs about US$ 800 /lb, offers the advantage of a high melting point. It can maintain reasonable...tubes, valves and thrusters of solid fluid propeller systems. Production of these components is however both expensive and difficult, as rhenium cannot

Paladin Integrated Management (PIM)

DTIC Science & Technology

2013-12-01

46:35 UNCLASSIFIED 4 Mission and Description The M109 Family of Vehicles (FOV) 155-millimeter / 39-caliber Self-Propelled Howitzer ( SPH ) provides...Teams, and Stryker Brigade Combat Teams. The M109 FOV Carrier Ammunition Tracked (CAT) provides armored ammunition supply support to the SPH ...fielded versions of the Army’s SPH and CAT. The Paladin Integrated Management (PIM) SPH and CAT will replace the M109A6 Paladin and M992A2 FAASV

PIMS(trademark): Remediation of Soil and Groundwater Contaminated With Metals. PIMS Remediation of Soil Contaminated with Lead at Camp Stanley Storage Activity, TX

DTIC Science & Technology

2003-08-01

4-3 Table 4.3 TCLP Results for Amended Soils.................................................................... 4-7 Table 4.4 Leachate ...100 million cubic yards, far exceeding that which can be disposed to landfills. Additionally, large quantities of lead-contaminated leachates ...acre demonstration site at SWMU B-20 for observations of efficacy by collection of leachates from shallow lysimeter monitoring wells. The field

Learning from the past for TB drug discovery in the future

PubMed Central

Mikušová, Katarína; Ekins, Sean

2016-01-01

Tuberculosis drug discovery has shifted in recent years from a primarily target-based approach to one that uses phenotypic high-throughput screens. As examples of this, through our EU-funded FP7 collaborations, New Medicines for Tuberculosis was target-based and our more-recent More Medicines for Tuberculosis project predominantly used phenotypic screening. From these projects we have examples of success (DprE1) and failure (PimA) going from drug to target and from target to drug, respectively. It is clear that we still have much to learn about the drug targets and the complex effects of the drugs on Mycobacterium tuberculosis. We propose a more integrated approach that learns from earlier drug discovery efforts that could help to move drug discovery forward. PMID:27717850

Computing thermal Wigner densities with the phase integration method

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

Beutier, J.; Borgis, D.; Vuilleumier, R.

2014-08-28

We discuss how the Phase Integration Method (PIM), recently developed to compute symmetrized time correlation functions [M. Monteferrante, S. Bonella, and G. Ciccotti, Mol. Phys. 109, 3015 (2011)], can be adapted to sampling/generating the thermal Wigner density, a key ingredient, for example, in many approximate schemes for simulating quantum time dependent properties. PIM combines a path integral representation of the density with a cumulant expansion to represent the Wigner function in a form calculable via existing Monte Carlo algorithms for sampling noisy probability densities. The method is able to capture highly non-classical effects such as correlation among the momenta andmore » coordinates parts of the density, or correlations among the momenta themselves. By using alternatives to cumulants, it can also indicate the presence of negative parts of the Wigner density. Both properties are demonstrated by comparing PIM results to those of reference quantum calculations on a set of model problems.« less

Study of soft magnetic iron cobalt based alloys processed by powder injection molding

NASA Astrophysics Data System (ADS)

Silva, Aline; Lozano, Jaime A.; Machado, Ricardo; Escobar, Jairo A.; Wendhausen, Paulo A. P.

As a near net shape process, powder injection molding (PIM) opens new possibilities to process Fe-Co alloys for magnetic applications. Due to the fact that PIM does not involve plastic deformation of the material during processing, we envisioned the possibility of eliminating vanadium (V), which is generally added to Fe-Co alloys to improve the ductility in order to enable its further shaping by conventional processes such as forging and cold rolling. In our investigation we have found out two main futures related to the elimination of V, which lead to a cost-benefit gain in manufacturing small magnetic components where high-saturation induction is needed at low frequencies. Firstly, the elimination of V enables the achievement of much better magnetic properties when alloys are processed by PIM. Secondly, a lower sintering temperature can be used when the alloy is processed starting with elemental Fe and Co powders without the addition of V.

Computing thermal Wigner densities with the phase integration method.

PubMed

Beutier, J; Borgis, D; Vuilleumier, R; Bonella, S

2014-08-28

We discuss how the Phase Integration Method (PIM), recently developed to compute symmetrized time correlation functions [M. Monteferrante, S. Bonella, and G. Ciccotti, Mol. Phys. 109, 3015 (2011)], can be adapted to sampling/generating the thermal Wigner density, a key ingredient, for example, in many approximate schemes for simulating quantum time dependent properties. PIM combines a path integral representation of the density with a cumulant expansion to represent the Wigner function in a form calculable via existing Monte Carlo algorithms for sampling noisy probability densities. The method is able to capture highly non-classical effects such as correlation among the momenta and coordinates parts of the density, or correlations among the momenta themselves. By using alternatives to cumulants, it can also indicate the presence of negative parts of the Wigner density. Both properties are demonstrated by comparing PIM results to those of reference quantum calculations on a set of model problems.

Plasma diagnostics of low pressure high power impulse magnetron sputtering assisted by electron cyclotron wave resonance plasma

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

Stranak, Vitezslav; University of South Bohemia, Institute of Physics and Biophysics, Branisovska 31, 370 05 Ceske Budejovice; Herrendorf, Ann-Pierra

2012-11-01

This paper reports on an investigation of the hybrid pulsed sputtering source based on the combination of electron cyclotron wave resonance (ECWR) inductively coupled plasma and high power impulse magnetron sputtering (HiPIMS) of a Ti target. The plasma source, operated in an Ar atmosphere at a very low pressure of 0.03 Pa, provides plasma where the major fraction of sputtered particles is ionized. It was found that ECWR assistance increases the electron temperature during the HiPIMS pulse. The discharge current and electron density can achieve their stable maximum 10 {mu}s after the onset of the HiPIMS pulse. Further, a highmore » concentration of double charged Ti{sup ++} with energies of up to 160 eV was detected. All of these facts were verified experimentally by time-resolved emission spectroscopy, retarding field analyzer measurement, Langmuir probe, and energy-resolved mass spectrometry.« less

Gilgamesh: A Multithreaded Processor-In-Memory Architecture for Petaflops Computing

NASA Technical Reports Server (NTRS)

Sterling, T. L.; Zima, H. P.

2002-01-01

Processor-in-Memory (PIM) architectures avoid the von Neumann bottleneck in conventional machines by integrating high-density DRAM and CMOS logic on the same chip. Parallel systems based on this new technology are expected to provide higher scalability, adaptability, robustness, fault tolerance and lower power consumption than current MPPs or commodity clusters. In this paper we describe the design of Gilgamesh, a PIM-based massively parallel architecture, and elements of its execution model. Gilgamesh extends existing PIM capabilities by incorporating advanced mechanisms for virtualizing tasks and data and providing adaptive resource management for load balancing and latency tolerance. The Gilgamesh execution model is based on macroservers, a middleware layer which supports object-based runtime management of data and threads allowing explicit and dynamic control of locality and load balancing. The paper concludes with a discussion of related research activities and an outlook to future work.

Promoter Engineering Reveals the Importance of Heptameric Direct Repeats for DNA Binding by Streptomyces Antibiotic Regulatory Protein-Large ATP-Binding Regulator of the LuxR Family (SARP-LAL) Regulators in Streptomyces natalensis.

PubMed

Barreales, Eva G; Vicente, Cláudia M; de Pedro, Antonio; Santos-Aberturas, Javier; Aparicio, Jesús F

2018-05-15

The biosynthesis of small-size polyene macrolides is ultimately controlled by a couple of transcriptional regulators that act in a hierarchical way. A Streptomyces antibiotic regulatory protein-large ATP-binding regulator of the LuxR family (SARP-LAL) regulator binds the promoter of a PAS-LuxR regulator-encoding gene and activates its transcription, and in turn, the gene product of the latter activates transcription from various promoters of the polyene gene cluster directly. The primary operator of PimR, the archetype of SARP-LAL regulators, contains three heptameric direct repeats separated by four-nucleotide spacers, but the regulator can also bind a secondary operator with only two direct repeats separated by a 3-nucleotide spacer, both located in the promoter region of its unique target gene, pimM A similar arrangement of operators has been identified for PimR counterparts encoded by gene clusters for different antifungal secondary metabolites, including not only polyene macrolides but peptidyl nucleosides, phoslactomycins, or cycloheximide. Here, we used promoter engineering and quantitative transcriptional analyses to determine the contributions of the different heptameric repeats to transcriptional activation and final polyene production. Optimized promoters have thus been developed. Deletion studies and electrophoretic mobility assays were used for the definition of DNA-binding boxes formed by 22-nucleotide sequences comprising two conserved heptameric direct repeats separated by four-nucleotide less conserved spacers. The cooperative binding of PimR SARP appears to be the mechanism involved in the binding of regulator monomers to operators, and at least two protein monomers are required for efficient binding. IMPORTANCE Here, we have shown that a modulation of the production of the antifungal pimaricin in Streptomyces natalensis can be accomplished via promoter engineering of the PAS-LuxR transcriptional activator pimM The expression of this gene is controlled by the Streptomyces antibiotic regulatory protein-large ATP-binding regulator of the LuxR family (SARP-LAL) regulator PimR, which binds a series of heptameric direct repeats in its promoter region. The structure and importance of such repeats in protein binding, transcriptional activation, and polyene production have been investigated. These findings should provide important clues to understand the regulatory machinery that modulates antibiotic biosynthesis in Streptomyces and open new possibilities for the manipulation of metabolite production. The presence of PimR orthologues encoded by gene clusters for different secondary metabolites and the conservation of their operators suggest that the improvements observed in the activation of pimaricin biosynthesis by Streptomyces natalensis could be extrapolated to the production of different compounds by other species. Copyright © 2018 Barreales et al.

Nineteenth International Microgravity Measurements Group Meeting

NASA Technical Reports Server (NTRS)

DeLombard, Richard (Compiler)

2000-01-01

The Microgravity Measurements Group meetings provide a forum for an exchange of information and ideas about various aspects of microgravity acceleration research in international microgravity research programs. These meetings are sponsored by the PI Microgravity Services (PIMS) project at the NASA Glenn Research Center. The 19th MGMG meeting was held 11-13 July 2000 at the Sheraton Airport Hotel in Cleveland, Ohio. The 44 attendees represented NASA, other space agencies, universities, and commercial companies; 8 of the attendees were international representatives from Japan, Italy, Canada, Russia, and Germany. Twenty-seven presentations were made on a variety of microgravity environment topics including the International Space Station (ISS), acceleration measurement and analysis results, science effects from microgravity accelerations, vibration isolation, free flyer satellites, ground testing, vehicle characterization, and microgravity outreach and education. The meeting participants also toured three microgravity-related facilities at the NASA Glenn Research Center. Contained within the minutes is the conference agenda, which indicates each speaker, the title of their presentation, and the actual time of their presentation. The minutes also include the charts for each presentation, which indicate the authors' name(s) and affiliation. In some cases, a separate written report was submitted and has been Included here

Proceedings of the Twentieth International Microgravity Measurements Group Meeting

NASA Technical Reports Server (NTRS)

DeLombard, Richard (Compiler)

2001-01-01

The International Microgravity Measurements Group annual meetings provide a forum for an exchange of information and ideas about various aspects of microgravity acceleration research in international microgravity research programs. These meetings are sponsored by the PI Microgravity Services (PIMS) project at the NASA Glenn Research Center. The twentieth MGMG meeting was held 7-9 August 2001 at the Hilton Garden Inn Hotel in Cleveland, Ohio. The 35 attendees represented NASA, other space agencies, universities, and commercial companies; eight of the attendees were international representatives from Canada, Germany, Italy, Japan, and Russia. Seventeen presentations were made on a variety of microgravity environment topics including the International Space Station (ISS), acceleration measurement and analysis results, science effects from microgravity accelerations, vibration isolation, free flyer satellites, ground testing, and microgravity outreach. Two working sessions were included in which a demonstration of ISS acceleration data processing and analyses were performed with audience participation. Contained within the minutes is the conference agenda which indicates each speaker, the title of their presentation, and the actual time of their presentation. The minutes also include the charts for each presentation which indicate the author's name(s) and affiliation. In some cases, a separate written report was submitted and has been included here.

Laboratory information management system for membrane protein structure initiative--from gene to crystal.

PubMed

Troshin, Petr V; Morris, Chris; Prince, Stephen M; Papiz, Miroslav Z

2008-12-01

Membrane Protein Structure Initiative (MPSI) exploits laboratory competencies to work collaboratively and distribute work among the different sites. This is possible as protein structure determination requires a series of steps, starting with target selection, through cloning, expression, purification, crystallization and finally structure determination. Distributed sites create a unique set of challenges for integrating and passing on information on the progress of targets. This role is played by the Protein Information Management System (PIMS), which is a laboratory information management system (LIMS), serving as a hub for MPSI, allowing collaborative structural proteomics to be carried out in a distributed fashion. It holds key information on the progress of cloning, expression, purification and crystallization of proteins. PIMS is employed to track the status of protein targets and to manage constructs, primers, experiments, protocols, sample locations and their detailed histories: thus playing a key role in MPSI data exchange. It also serves as the centre of a federation of interoperable information resources such as local laboratory information systems and international archival resources, like PDB or NCBI. During the challenging task of PIMS integration, within the MPSI, we discovered a number of prerequisites for successful PIMS integration. In this article we share our experiences and provide invaluable insights into the process of LIMS adaptation. This information should be of interest to partners who are thinking about using LIMS as a data centre for their collaborative efforts.

Downregulation of microRNA-33a promotes cyclin-dependent kinase 6, cyclin D1 and PIM1 expression and gastric cancer cell proliferation

PubMed Central

WANG, YUDONG; ZHOU, XINLIANG; SHAN, BAOEN; HAN, JING; WANG, FEIFEI; FAN, XIAOJIE; LV, YALEI; CHANG, LIANG; LIU, WEI

2015-01-01

Although microRNA-33 (miR-33) family members are known to be involved in the regulation and balancing of cholesterol metabolism, fatty acid oxidation and insulin signaling, their functions in carcinogenesis are controversial and the underlying mechanisms have remained elusive. Gastric cancer is the fourth most common malignancy in the world; however, the dysregulation and function of miR-33 family members in gastric cancer have not been extensively studied. The present study reported that a miR-33 family member, miR-33a, was significantly downregulated in gastric cancer tissues and gastric cancer cell lines. Of note, the expression of miR-33a was inversely correlated with pathological differentiation and metastasis as well as gastric cancer biomarker CA199. A cell-counting kit-8 assay showed that transfection of the SGC-7901 gastric cell line with miR-33a-overexpression plasmid inhibited the capability of the cells to proliferate. Furthermore, overexpression of miR-33a led to cell cycle arrest of SGC-7901 cells in G1 phase. In addition, a luciferase reporter assay showed that miR-33a directly targeted cyclin-dependent kinase 6 (CDK6), cyclin D1 (CCND1) and serine/threonine kinase PIM-1. In gastric cancer specimens, the reduced expression of miR-33a was associated with increased expression of CDK-6, CCND1 and PIM1. However, only PIM1 expression was significantly increased in cancer tissues compared with that in their adjacent tissues. The present study revealed that miR-33a was downregulated in gastric cancer tissues and cell lines, while forced overexpression of miR-33a decreased CDK-6, CCND1 and PIM1 expression to inhibit gastric cancer cell proliferation by causing G1 phase arrest. miR-33a overexpression may therefore resemble an efficient strategy for gastric cancer therapy. PMID:26352175

Radiometric Measurements by the MIDAS III System at Key West. Volume I. Cloud Backgrounds.

DTIC Science & Technology

1979-09-01

13 13.3 System Relative Spectral Response - Filter No. 2 5(4.4-4.77 pim ) ............................................. 14 3.4 System Relative Spectral...Response - Filter No. 5 (3.8-4.2 pim ) .............................................. 15 3.5 System Relative Spectral Response - Filter No. 6 (3.4-4.3...5 dat a was recorded dirtxet l ott t he recordinig osc ml logrtt1 Witereis tilt- 8-13 data was recorded on t tiet I ape, recorders i xst itd laxter p

Littoral Combat Ship (LCS) Mission Packages: Determining the Best Mix

DTIC Science & Technology

2008-03-01

to thank CAPT Doug Otte , USN, CDR Doug Burton, USN, Colonel Ed Lesnowicz, USMC (Ret.), Lloyd Brown, LCDR Scott Hattway, USN, and LT John Baggett...clear it of any surface threats. Upon commencement, SUW LCS are following assigned PIM into the channel with an embarked MH-60R airborne. Upon enemy... PIM . Since LCS is a focused mission platform, a SUW LCS will not pursue anything other than a surface threat (i.e. it will not pursue, and cannot

Plasma ``anti-assistance'' and ``self-assistance'' to high power impulse magnetron sputtering

NASA Astrophysics Data System (ADS)

Anders, André; Yushkov, Georgy Yu.

2009-04-01

A plasma assistance system was investigated with the goal to operate high power impulse magnetron sputtering (HiPIMS) at lower pressure than usual, thereby to enhance the utilization of the ballistic atoms and ions with high kinetic energy in the film growth process. Gas plasma flow from a constricted plasma source was aimed at the magnetron target. Contrary to initial expectations, such plasma assistance turned out to be contraproductive because it led to the extinction of the magnetron discharge. The effect can be explained by gas rarefaction. A better method of reducing the necessary gas pressure is operation at relatively high pulse repetition rates where the afterglow plasma of one pulse assists in the development of the next pulse. Here we show that this method, known from medium-frequency (MF) pulsed sputtering, is also very important at the much lower pulse repetition rates of HiPIMS. A minimum in the possible operational pressure is found in the frequency region between HiPIMS and MF pulsed sputtering.

Material flow data for numerical simulation of powder injection molding

NASA Astrophysics Data System (ADS)

Duretek, I.; Holzer, C.

2017-01-01

The powder injection molding (PIM) process is a cost efficient and important net-shape manufacturing process that is not completely understood. For the application of simulation programs for the powder injection molding process, apart from suitable physical models, exact material data and in particular knowledge of the flow behavior are essential in order to get precise numerical results. The flow processes of highly filled polymers are complex. Occurring effects are very hard to separate, like shear flow with yield stress, wall slip, elastic effects, etc. Furthermore, the occurrence of phase separation due to the multi-phase composition of compounds is quite probable. In this work, the flow behavior of a 316L stainless steel feedstock for powder injection molding was investigated. Additionally, the influence of pre-shearing on the flow behavior of PIM-feedstocks under practical conditions was examined and evaluated by a special PIM injection molding machine rheometer. In order to have a better understanding of key factors of PIM during the injection step, 3D non-isothermal numerical simulations were conducted with a commercial injection molding simulation software using experimental feedstock properties. The simulation results were compared with the experimental results. The mold filling studies amply illustrate the effect of mold temperature on the filling behavior during the mold filling stage. Moreover, the rheological measurements showed that at low shear rates no zero shear viscosity was observed, but instead the viscosity further increased strongly. This flow behavior could be described with the Cross-WLF approach with Herschel-Bulkley extension very well.

Ingredientes Farmacéuticos Activos Potencialmente Inapropiados en Adultos Mayores: Lista IFAsPIAM: Panel de Consenso Argentino.

PubMed

Marzi, Marta M; Pires, Miryam S; Quaglia, Nora B

2018-04-18

To perform a list agreed by Argentinean experts and adapted to the local context containing potentially inappropriate (PI) medications in old people (OP) usingthe Delphi consensus technique optimized for this subject. A preliminary list of potentially inappropriate medications (PIM) was drawn up based on foreign PIM lists and a selective search in the scientific literature. The iterative Delphi process was used to submit the active pharmaceutical ingredients (APIs) of the preliminary PIM list to the panel of Argentinean experts. The analysis of theanswers to determine the arrival to the consensus was carried out applying three criteria specially defined for this purpose. After two Delphi rounds, it was not reached agreement about 12 APIs. The List of explicit criteria for PIAPIs for use in OP (IFAsPIAM List) was finally constituted by 128 APIs corresponding to 9 groups of the ATC classification system to which they were organized. In addition to each API, information justifying the unfavorable benefit/risk profile and therapeutic alternatives or recommendations/precautions was recorded. The group with the most PI APIs was N (NervousSystem) (60; 47%) followed by groups C (Cardiovascular) and M (Musculoskeletal). This study presents the first Latin American list of PIM in OP developed using an expert consensus technique. The IFAs PIAM List would contribute to the rational use of drugs in elderly population, constituting a valuable tool in Argentinean public health. Copyright © 2018. Published by Elsevier Inc.

MicroRNA-101-3p suppresses cell proliferation, invasion and enhances chemotherapeutic sensitivity in salivary gland adenoid cystic carcinoma by targeting Pim-1

PubMed Central

Liu, Xiao-Yu; Liu, Zhi-Jian; He, Hong; Zhang, Chen; Wang, Yun-Long

2015-01-01

MicroRNAs (miRNAs) play critical roles in carcinogenesis and tumor progression. Recent research has revealed miR-101-3p as an important regulator in several cancers. Nevertheless, its function in salivary gland Adenoid cystic carcinoma (ACC), a relatively rare malignance with poor long-term survival rate arisen in head and neck region, remain unknown. In this study, down-regulated miR-101-3p expression was detected in ACC tissues and ACC cell lines with high potential for metastasis. Ectopic expression of miR-101-3p significantly repressed the invasion, proliferation, colony formation, and formation of nude mice xenografts and induced potent apoptosis in ACC cell lines. The provirus integration site for Moloney murine leukemia virus 1 (Pim-1) oncogene was subsequently confirmed as a direct target gene of miR-101-3p in ACC. Functional restoration assays revealed that miR-101-3p inhibits cell growth and invasion by directly decreasing Pim-1 expression. Protein levels of Survivin, Cyclin D1 and β-catenin were also down-regulated by miR-101-3p. miR-101-3p enhanced the sensitivity of cisplatin in ACC cell lines. Taken together, our results demonstrate that the novel miR-101-3p/Pim-1 axis provides excellent insights into the carcinogenesis and tumor progression of ACC and may be a promising therapeutic target for this type of cancer. PMID:26693056

Impact of 2015 Update to the Beers Criteria on Estimates of Prevalence and Costs Associated with Potentially Inappropriate Use of Antimuscarinics for Overactive Bladder.

PubMed

Suehs, Brandon T; Davis, Cralen; Ng, Daniel B; Gooch, Katherine

2017-07-01

Research has demonstrated that the use of potentially inappropriate medication (PIM) is highly prevalent among older individuals and may lead to increased healthcare costs, adverse drug reactions, hospitalizations, and mortality. The purpose of this study was to examine the impact of the 2015 updates to the Beers Criteria on estimates of prevalence and cost associated with potentially inappropriate use of antimuscarinic medications indicated for treatment of overactive bladder (OAB). A retrospective database analysis was conducted using a historical cohort design and including data collected between 2007 and 2013. Claims data were used to identify Medicare Advantage patients aged ≥65 years newly initiated on antimuscarinic OAB treatment. Patients were classified with potentially inappropriate use of antimuscarinic OAB drugs based on either the 2012 Beers Criteria or the 2015 Beers Criteria. Prevalence of PIM at the time of antimuscarinic initiation was determined. Bivariate comparisons of healthcare costs and medical condition burden were conducted to compare the marginal groups of patients (who qualified based on the 2012 Beers Criteria only or the 2015 Beers Criteria only). Differences in healthcare costs for patients with and without potentially inappropriate use of urinary antimuscarinics based on the 2012 and 2015 Beers Criteria were also examined. Of 66,275 patients, overall prevalence of potentially inappropriate use of OAB antimuscarinics was higher using 2015 Beers Criteria than when using the 2012 Beers Criteria (25.0 vs. 20.6%). Dementia was the most common PIM-qualifying condition under both versions. The 2015 Beers Criteria identified more females, more White people, and a younger population with PIM. Comorbid medical condition burden was lower using the 2015 Beers Criteria. The 2015 Beers Criteria only group had lower median unadjusted healthcare costs ($7104 vs. 8301; p < 0.001). The incremental net cost associated with potentially inappropriate use of antimuscarinic medication was higher under the 2012 Beers Criteria than under the 2015 Beers Criteria. In this cohort of patients newly initiated on antimuscarinic OAB treatment, substantial overlap of patients identified with PIM based on the 2015 Beers Criteria compared with the 2012 Beers Criteria was observed. In addition, the findings suggest that, when applied to antimuscarinic initiators, the 2015 Beers Criteria result in a greater prevalence of PIM and the identification of patients with less overall medical morbidity than the 2012 Beers Criteria.

Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth.

PubMed

Glass, Lisa N; Swapna, Ganduri; Chavadi, Sivagami Sundaram; Tufariello, JoAnn M; Mi, Kaixia; Drumm, Joshua E; Lam, TuKiet T; Zhu, Guofeng; Zhan, Chenyang; Vilchéze, Catherine; Arcos, Jesus; Chen, Yong; Bi, Lijun; Mehta, Simren; Porcelli, Steven A; Almo, Steve C; Yeh, Syun-Ru; Jacobs, William R; Torrelles, Jordi B; Chan, John

2017-07-01

We have previously shown that the Mycobacterium tuberculosis universal stress protein Rv2623 regulates mycobacterial growth and may be required for the establishment of tuberculous persistence. Here, yeast two-hybrid and affinity chromatography experiments have demonstrated that Rv2623 interacts with one of the two forkhead-associated domains (FHA I) of Rv1747, a putative ATP-binding cassette transporter annotated to export lipooligosaccharides. FHA domains are signaling protein modules that mediate protein-protein interactions to modulate a wide variety of biological processes via binding to conserved phosphorylated threonine (pT)-containing oligopeptides of the interactors. Biochemical, immunochemical and mass spectrometric studies have shown that Rv2623 harbors pT and specifically identified threonine 237 as a phosphorylated residue. Relative to wild-type Rv2623 (Rv2623WT), a mutant protein in which T237 has been replaced with a non-phosphorylatable alanine (Rv2623T237A) exhibits decreased interaction with the Rv1747 FHA I domain and diminished growth-regulatory capacity. Interestingly, compared to WT bacilli, an M. tuberculosis Rv2623 null mutant (ΔRv2623) displays enhanced expression of phosphatidyl-myo-inositol mannosides (PIMs), while the ΔRv1747 mutant expresses decreased levels of PIMs. Animal studies have previously shown that ΔRv2623 is hypervirulent, while ΔRv1747 is growth-attenuated. Collectively, these data have provided evidence that Rv2623 interacts with Rv1747 to regulate mycobacterial growth; and this interaction is mediated via the recognition of the conserved Rv2623 pT237-containing FHA-binding motif by the Rv1747 FHA I domain. The divergent aberrant PIM profiles and the opposing in vivo growth phenotypes of ΔRv2623 and ΔRv1747, together with the annotated lipooligosaccharide exporter function of Rv1747, suggest that Rv2623 interacts with Rv1747 to modulate mycobacterial growth by negatively regulating the activity of Rv1747; and that Rv1747 might function as a transporter of PIMs. Because these glycolipids are major mycobacterial cell envelope components that can impact on the immune response, our findings raise the possibility that Rv2623 may regulate bacterial growth, virulence, and entry into persistence, at least in part, by modulating the levels of bacillary PIM expression, perhaps through negatively regulating the Rv1747-dependent export of the immunomodulatory PIMs to alter host-pathogen interaction, thereby influencing the fate of M. tuberculosis in vivo.

Infrared Measurement Variability Analysis.

DTIC Science & Technology

1980-09-01

collecting optics of the measurement system. The first equation for tile blackbody experiment has the form 4.0 pim _ Ae W ,T) r(X,D) 3.5 pm - 4.0 pm JrD2 f3.5...potential for noise reduction by identifying and reducing contributing system effects. The measurement variance ott . of an infinite population of possible...irradiance can be written 4.0 pm I r()A A+ A ) 2 4.0 X C1(, = W(XT + AT)d 3.5 pim I since c + Af =2 r +Ar I Using the two expressions juSt devclopCd

Investigation of Methods to Eliminate Voltage Delay in Li/SOCl2 Cells.

DTIC Science & Technology

1980-05-01

of storage at 550C the surface was completely covered with cubic crystals averaging about 8 pim on an edge (Figure 24). The lithium surface stored at...completely covered with cubic crystals, showing no smooth undercoating at all (Figure 25). The average crystal diameter was approximately 3.3 pim , with a...used. ithi timl acgu ire0d A Ci yst al I me surt ace, oil dr n torage at elevated temlper aI Ite t. T[he out lace, showed ch[ ott ine by EPAC except

Pro-inflammatory mediators disrupt glucose homeostasis in airway surface liquid ‡

PubMed Central

Garnett, James P.; Nguyen, Trang T.; Moffatt, James D.; Pelham, Elizabeth R.; Kalsi, Kameljit K.; Baker, Emma H.; Baines, Deborah L.

2012-01-01

The glucose concentration of the airway surface liquid (ASL) is much lower than blood and is tightly regulated by the airway epithelium. ASL glucose is elevated in patients with viral colds, cystic fibrosis, chronic obstructive pulmonary disease (COPD) and asthma. Elevated ASL glucose is also associated with increased incidence of respiratory infection. However, the mechanism by which ASL glucose increases under inflammatory conditions is unknown. The aim of this study was to investigate the effect of pro-inflammatory mediators (PIMs) on the mechanisms governing airway glucose homeostasis in polarised monolayers of human airway (H441) and primary human bronchial epithelial (HBE) cells. Monolayers were treated with TNF-α, IFN-γ and LPS over 72 hours. PIM treatment led to increase in ASL glucose concentration and significantly reduced H441 and HBE transepithelial resistance (RT). This decline in RT was associated with an increase in paracellular permeability of glucose. Similar enhanced rates of paracellular glucose flux were also observed across excised trachea from LPS-treated mice. Interestingly, PIMs enhanced glucose uptake across the apical, but not the basolateral, membrane of H441 and HBE monolayers. This increase was predominantly via phloretin-sensitive GLUT-mediated uptake, which coincided with an increase in GLUT2 and GLUT10 abundance. In conclusion, exposure of airway epithelial monolayers to PIMs results in increased paracellular glucose flux, and apical GLUT-mediated glucose uptake. However uptake was insufficient to limit glucose accumulation in ASL. These data provide for the first time, a mechanism to support clinical findings that ASL glucose concentration is increased in patients with airway inflammation. PMID:22623330

Interleukin-27 induces the endothelial differentiation in Sca-1+ cardiac resident stem cells.

PubMed

Tanaka, Tomohiro; Obana, Masanori; Mohri, Tomomi; Ebara, Masaki; Otani, Yuta; Maeda, Makiko; Fujio, Yasushi

2015-10-01

Cytokines play important roles in cardiac repair and regeneration. Recently, we demonstrated that interleukin (IL)-6 family cytokines induce the endothelial differentiation of Sca-1+ cardiac resident stem cells through STAT3/Pim-1 signaling pathway. In contrast, the biological functions of IL-12 family cytokines in heart remain to be elucidated, though they show structural homology with IL-6. In the present study, we examined the effects of IL-12 family cytokines on the transdifferentiation of cardiac Sca-1+ cells into cardiac cells. RT-PCR analyses revealed that IL-27 receptor α (IL-27Rα), but not IL-12R or IL-23R, was expressed in cardiac Sca-1+ cells. The transcript expression of IL-27 was elevated in murine hearts in cardiac injury models. Intriguingly, IL-27 stimulation for 14 days induced the endothelial cell (EC) marker genes, such as CD-31 and VE-cadherin. Immunoblot analyses clarified that IL-27 treatment rapidly phosphorylated STAT3. IL-27 upregulated the expression of Pim-1, but the overexpression of dominant negative STAT3 abrogated the induction of Pim-1 by IL-27. Finally, adenoviral transfection of dominant negative Pim-1 inhibited IL-27-induced EC differentiation of cardiac Sca-1+ cells. These findings demonstrated that IL-27 promoted the commitment of cardiac stem cells into the EC lineage, possibly leading to neovascularization as a novel biological function. IL-27 could not only regulate the inflammation but also contribute to the maintenance of the tissue homeostasis through stem cell differentiation at inflammatory sites. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ion mass spectrometry investigations of the discharge during reactive high power pulsed and direct current magnetron sputtering of carbon in Ar and Ar/N{sub 2}

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

Schmidt, S.; Greczynski, G.; Jensen, J.

2012-07-01

Ion mass spectrometry was used to investigate discharges formed during high power impulse magnetron sputtering (HiPIMS) and direct current magnetron sputtering (DCMS) of a graphite target in Ar and Ar/N{sub 2} ambient. Ion energy distribution functions (IEDFs) were recorded in time-averaged and time-resolved mode for Ar{sup +}, C{sup +}, N{sub 2}{sup +}, N{sup +}, and C{sub x}N{sub y}{sup +} ions. An increase of N{sub 2} in the sputter gas (keeping the deposition pressure, pulse width, pulse frequency, and pulse energy constant) results for the HiPIMS discharge in a significant increase in C{sup +}, N{sup +}, and CN{sup +} ion energies.more » Ar{sup +}, N{sub 2}{sup +}, and C{sub 2}N{sup +} ion energies, in turn, did not considerably vary with the changes in working gas composition. The HiPIMS process showed higher ion energies and fluxes, particularly for C{sup +} ions, compared to DCMS. The time evolution of the plasma species was analyzed for HiPIMS and revealed the sequential arrival of working gas ions, ions ejected from the target, and later during the pulse-on time molecular ions, in particular CN{sup +} and C{sub 2}N{sup +}. The formation of fullerene-like structured CN{sub x} thin films for both modes of magnetron sputtering is explained by ion mass-spectrometry results and demonstrated by transmission electron microscopy as well as diffraction.« less

Mixed-Penetrant Sorption in Ultrathin Films of Polymer of Intrinsic Microporosity PIM-1.

PubMed

Ogieglo, Wojciech; Furchner, Andreas; Ghanem, Bader; Ma, Xiaohua; Pinnau, Ingo; Wessling, Matthias

2017-11-02

Mixed-penetrant sorption into ultrathin films of a superglassy polymer of intrinsic microporosity (PIM-1) was studied for the first time by using interference-enhanced in situ spectroscopic ellipsometry. PIM-1 swelling and the concurrent changes in its refractive index were determined in ultrathin (12-14 nm) films exposed to pure and mixed penetrants. The penetrants included water, n-hexane, and ethanol and were chosen on the basis of their significantly different penetrant-penetrant and penetrant-polymer affinities. This allowed studying microporous polymer responses at diverse ternary compositions and revealed effects such as competition for the sorption sites (for water/n-hexane or ethanol/n-hexane) or enhancement in sorption of typically weakly sorbing water in the presence of more highly sorbing ethanol. The results reveal details of the mutual sorption effects which often complicate comprehension of glassy polymers' behavior in applications such as high-performance membranes, adsorbents, or catalysts. Mixed-penetrant effects are typically very challenging to study directly, and their understanding is necessary owing to a broadly recognized inadequacy of simple extrapolations from measurements in a pure component environment.

Solution-Based 3D Printing of Polymers of Intrinsic Microporosity.

PubMed

Zhang, Fengyi; Ma, Yao; Liao, Jianshan; Breedveld, Victor; Lively, Ryan P

2018-05-28

Current additive manufacturing methods have significant limitations in the classes of compatible polymers. Many polymers of significant technological interest cannot currently be 3D printed. Here, a generalizable method for 3D printing of viscous tenary polymer solutions (polymer/solvent/nonsolvent) is applied to both "intrinsically porous" (a polymer of intrinsic microporosity, PIM-1) and "intrinsically nonporous" (cellulose acetate) polymers. Successful ternary ink formulations require balancing of solution thermodynamics (phase separation), mass transfer (solvent evaporation), and rheology. As a demonstration, a microporous polymer (PIM-1) incompatible with current additive manufacturing technologies is 3D printed into a high-efficiency mass transfer contactor exhibiting hierarchical porosity ranging from sub-nanometer to millimeter pores. Short contactors (1.27 cm) can fully purify (<1 ppm) toluene vapor (1000 ppm) in N 2 gas for 1.7 h, which is six times longer than PIM-1 in traditional structures, and more than 4000 times the residence time of gas in the contactor. This solution-based additive manufacturing approach greatly extends the range of 3D-printable materials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Real-time monitoring of trace-level VOCs by an ultrasensitive compact lamp-based VUV photoionization mass spectrometer

NASA Astrophysics Data System (ADS)

Sun, W. Q.; Shu, J. N.; Zhang, P.; Li, Z.; Li, N. N.; Liang, M.; Yang, B.

2015-06-01

In this study, we report on the development of a compact lamp-based vacuum ultraviolet (VUV) photoionization mass spectrometer (PIMS; hereafter referred to as VUV-PIMS) in our laboratory; it is composed of a radio frequency-powered VUV lamp, a VUV photoionizer, an ion-immigration region, and a reflection time-of-flight mass spectrometer. By utilizing the novel photoionizer consisting of a photoionization cavity and a VUV light baffle, extremely low background noise was obtained. An ultrasensitive detection limit (2σ) of 3 pptv was achieved for benzene after an acquisition time of 10 s. To examine its potential for application in real-time sample monitoring, the developed VUV-PIMS was employed for the continuous measurement of urban air for six days in Beijing, China. Strong signals of trace-level volatile organic compounds such as benzene and its alkylated derivatives were observed in the mass spectra. These initial experimental results reveal that the instrument can be used for the online monitoring of trace-level species in the atmosphere.

A review of micro-powder injection moulding as a microfabrication technique

NASA Astrophysics Data System (ADS)

Attia, Usama M.; Alcock, Jeffrey R.

2011-04-01

Micro-powder injection moulding (µPIM) is a fast-developing micro-manufacturing technique for the production of metal and ceramic components. Shape complexity, dimensional accuracy, replication fidelity, material variety combined with high-volume capabilities are some of the key advantages of the technology. This review assesses the capabilities and limitations of µPIM as a micro-manufacturing technique by reviewing the latest developments in the area and by considering potential improvements. The basic elements of the process chain, variant processes and simulation attempts are discussed and evaluated. Challenges and research gaps are highlighted, and potential areas for improvement are presented.

PIM1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

DTIC Science & Technology

2008-10-31

2007) C«t Pr. T«K:J1 r. 587-605 CaUtr«M, F. I . |200S> Oil . te- Tx\\u< 35.443-582 I ..-:tiatr.-ir, C.Iixo;, X. Cfitniti t,B<nor V..Dcrtgovsu, V,Chat...control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. I . REPORT DATE (DD-MM-YYYY) 31-10-2008 2. REPORT TYPE Annual 3. DATES COVERED...reporting period a number of studies were undertaken to characterize Fig. 4. Modulation of docetaxel cell kill by enforced expression of pim-1 cDNAs. 1 i

Evaporation-assisted high-power impulse magnetron sputtering: The deposition of tungsten oxide as a case study

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

Hemberg, Axel; Dauchot, Jean-Pierre; Snyders, Rony

2012-07-15

The deposition rate during the synthesis of tungsten trioxide thin films by reactive high-power impulse magnetron sputtering (HiPIMS) of a tungsten target increases, above the dc threshold, as a result of the appropriate combination of the target voltage, the pulse duration, and the amount of oxygen in the reactive atmosphere. This behavior is likely to be caused by the evaporation of the low melting point tungsten trioxide layer covering the metallic target in such working conditions. The HiPIMS process is therefore assisted by thermal evaporation of the target material.

Attenuation of Electromagnetic Radiation by Haze, Fog, Clouds, and Rain

DTIC Science & Technology

1975-04-01

transmission data of Gebbie etal,(3 Gibbons (27) suggests that ai = 0.7 in the wavelength range from 0.61 to 11.48 pim regardless of the meteorological...attenuation at 10 Um becomes 10 to 100 times smaller than at 0.5 jim. It can be also observed that the 8 to 12 pm band is preferable to the 3 to 5 pim ...Water Aerosols and Fog-," Arl. ¢ Ott ., Vol. 9, 1970, pp. 2000-2006. 33. Gebbie, If. A., ot al., "Atmospheric Transmission in the 1 to 14P Region," Pro

Analysis of ISS Plasma Interaction

NASA Technical Reports Server (NTRS)

Reddell, Brandon; Alred, John; Kramer, Leonard; Mikatarian, Ron; Minow, Joe; Koontz, Steve

2006-01-01

To date, the International Space Station (ISS) has been one of the largest objects flown in lower earth orbit (LEO). The ISS utilizes high voltage solar arrays (160V) that are negatively grounded leading to pressurized elements that can float negatively with respect to the plasma. Because laboratory measurements indicate a dielectric breakdown potential difference of 80V, arcing could occur on the ISS structure. To overcome the possibility of arcing and clamp the potential of the structure, two Plasma Contactor Units (PCUs) were designed, built, and flown. Also a limited amount of measurements of the floating potential for the present ISS configuration were made by a Floating Potential Probe (FPP), indicating a minimum potential of 24 Volts at the measurement location. A predictive tool, the ISS Plasma Interaction Model (PIM) has been developed accounting for the solar array electron collection, solar array mast wire and effective conductive area on the structure. The model has been used for predictions of the present ISS configuration. The conductive area has been inferred based on available floating potential measurements. Analysis of FPP and PCU data indicated distribution of the conductive area along the Russian segment of the ISS structure. A significant input to PIM is the plasma environment. The International Reference Ionosphere (IRI 2001) was initially used to obtain plasma temperature and density values. However, IRI provides mean parameters, leading to difficulties in interpretation of on-orbit data, especially at eclipse exit where maximum charging can occur. This limits our predicative capability. Satellite and Incoherent Scatter Radar (ISR) data of plasma parameters have also been collected. Approximately 130,000 electron temperature (Te) and density (Ne) pairs for typical ISS eclipse exit conditions have been extracted from the reduced Langmuir probe data flown aboard the NASA DE-2 satellite. Additionally, another 18,000 Te and Ne pairs of ISR data from several radar locations around the globe were used to assure consistency of the satellite data. PIM predictions for ISS charging made with this data correlated very well with FPP data, indicating that the general physics of spacecraft charging with high voltage solar arrays have been captured. The predictions also provided the probabilities of occurrences for ISS charging. These probabilities give a numerical measure of the number of times when the ISS will approach or exceed the vehicle plasma hazard conditions for each configuration. In this paper we shall present the interaction mechanisms between the ISS and the surrounding plasma and give an overview of the PIM components. PIM predictions are compared with available data followed by a discussion of the variability of plasma parameters and the conductive area on the ISS. The ISS PIM will be further tested and verified as data from the Floating Potential Measurement Unit become available, and construction of the ISS continues.

Reduced atomic shadowing in HiPIMS: Role of the thermalized metal ions

NASA Astrophysics Data System (ADS)

Oliveira, João Carlos; Ferreira, Fábio; Anders, André; Cavaleiro, Albano

2018-03-01

In magnetron sputtering, the ability to tailor film properties depends primarily on the control of the flux of particles impinging on the growing film. Among deposition mechanisms, the shadowing effect leads to the formation of a rough surface and a porous, columnar microstructure. Re-sputtered species may be re-deposited in the valleys of the films surface and thereby contribute to a reduction of roughness and to fill the underdense regions. Both effects are non-local and they directly compete to shape the final properties of the deposited films. Additional control of the bombarding flux can be obtained by ionizing the sputtered flux, because ions can be controlled with respect to their energy and impinging direction, such as in High-Power Impulse Magnetron Sputtering (HiPIMS). In this work, the relation between ionization of the sputtered species and thin film properties is investigated in order to identify the mechanisms which effectively influence the shadowing effect in Deep Oscillation Magnetron Sputtering (DOMS), a variant of HiPIMS. The properties of two Cr films deposited using the same averaged target power by d.c. magnetron sputtering and DOMS have been compared. Additionally, the angle distribution of the Cr species impinging on the substrate was simulated using Monte Carlo-based programs while the energy distribution of the energetic particles bombarding the substrate was evaluated by energy-resolved mass analysis. It was found that the acceleration of the thermalized chromium ions at the substrate sheath in DOMS significantly reduces the high angle component of their impinging angle distribution and, thus, efficiently reduces atomic shadowing. Therefore, a high degree of ionization in HiPIMS results in almost shadowing effect-free film deposition and allows us to deposit dense and compact films without the need of high energy particle bombardment during growth.

Tackling membrane fouling in microalgae filtration using nylon 6,6 nanofiber membrane.

PubMed

Bilad, M R; Azizo, A S; Wirzal, M D H; Jia Jia, L; Putra, Z A; Nordin, N A H M; Mavukkandy, M O; Jasni, M J F; Yusoff, A R M

2018-06-06

Microalgae technology, if managed properly, has promising roles in solving food-water-energy nexus. The Achilles' heel is, however, to lower the costs associated with cultivation and harvesting. As a favorable technique, application of membrane process is strongly limited by membrane fouling. This study evaluates performance of nylon 6,6 nanofiber membrane (NFM) to a conventional polyvinylidene fluoride phase inverted membrane (PVDF PIM) for filtration of Chlorella vulgaris. Results show that nylon 6,6 NFM is superhydrophilic, has higher size of pore opening (0.22 vs 0.18 μm) and higher surface pore density (23 vs 18 pores/μm 2 ) leading to higher permeance (1018 vs 493 L/m 2 hbar) and better fouling resistant. Such advantages help to outperform the filterability of PVDF PIM by showing much higher steady-state permeance (286 vs 120 L/m 2 hbar), with comparable biomass retention. In addition, unlike for PVDF PIM, imposing longer relaxation cycles further enhances the performance of the NFM (i.e., 178 L/m 2 hbar for 0.5 min and 236 L/m 2 hbar for 5 min). Overall findings confirm the advantages of nylon 6,6 NFM over the PVDF PIM. Such advantages can help to reduce required membrane area and specific aeration demand by enabling higher flux and lowering aeration rate. Nevertheless, developments of nylon 6,6 NFM material with respect to its intrinsic properties, mechanical strength and operational conditions of the panel can still be explored to enhance its competitiveness as a promising fouling resistant membrane material for microalgae filtration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Optical and Gravimetric Partitioning of Coastal Ocean Suspended Particulate Inorganic Matter (PIM)

NASA Astrophysics Data System (ADS)

Stavn, R. H.; Zhang, X.; Falster, A. U.; Gray, D. J.; Rick, J. J.; Gould, R. W., Jr.

2016-02-01

Recent work on the composition of suspended particulates of estuarine and coastal waters increases our capabilities to investigate the biogeochemal processes occurring in these waters. The biogeochemical properties associated with the particulates involve primarily sorption/desorption of dissolved matter onto the particle surfaces, which vary with the types of particulates. Therefore, the breakdown into chemical components of suspended matter will greatly expand the biogeochemistry of the coastal ocean region. The gravimetric techniques for these studies are here expanded and refined. In addition, new optical inversions greatly expand our capabilities to study spatial extent of the components of suspended particulate matter. The partitioning of a gravimetric PIM determination into clay minerals and amorphous silica is aided by electron microprobe analysis. The amorphous silica is further partitioned into contributions by detrital material and by the tests of living diatoms based on an empirical formula relating the chlorophyll content of cultured living diatoms in log phase growth to their frustules determined after gravimetric analysis of the ashed diatom residue. The optical inversion of composition of suspended particulates is based on the entire volume scattering function (VSF) measured in the field with a Multispectral Volume Scattering Meter and a LISST 100 meter. The VSF is partitioned into an optimal combination of contributions by particle subpopulations, each of which is uniquely represented by a refractive index and a log-normal size distribution. These subpopulations are aggregated to represent the two components of PIM using the corresponding refractive indices and sizes which also yield a particle size distribution for the two components. The gravimetric results of partitioning PIM into clay minerals and amorphous silica confirm the optical inversions from the VSF.

Characterization and device applications of ZnO films deposited by high power impulse magnetron sputtering (HiPIMS)

NASA Astrophysics Data System (ADS)

Partridge, J. G.; Mayes, E. L. H.; McDougall, N. L.; Bilek, M. M. M.; McCulloch, D. G.

2013-04-01

ZnO films have been reactively deposited on sapphire substrates at 300 °C using a high impulse power magnetron sputtering deposition system and characterized structurally, optically and electronically. The unintentionally doped n-type ZnO films exhibit high transparency, moderate carrier concentration (˜5 × 1018 cm-3) and a Hall mobility of 8.0 cm2 V-1 s-1, making them suitable for electronic device applications. Pt/ZnO Schottky diodes formed on the HiPIMS deposited ZnO exhibited rectification ratios up to 104 at ±2 V and sensitivity to UV light.

Ion density evolution in a high-power sputtering discharge with bipolar pulsing

NASA Astrophysics Data System (ADS)

Britun, N.; Michiels, M.; Godfroid, T.; Snyders, R.

2018-06-01

Time evolution of sputtered metal ions in high power impulse magnetron sputtering (HiPIMS) discharge with a positive voltage pulse applied after a negative one (regime called "bipolar pulse HiPIMS"—BPH) is studied using 2-D density mapping. It is demonstrated that the ion propagation dynamics is mainly affected by the amplitude and duration of the positive pulse. Such effects as ion repulsion from the cathode and the ionization zone shrinkage due to electron drift towards the cathode are clearly observed during the positive pulse. The BPH mode also alters the film crystallographic structure, as observed from X-ray diffraction analysis.

Atmospheric Transmission Modeling: Proposed Aerosol Methodology with Application to the Grafenwoehr Atmospheric Optics Data Base

DTIC Science & Technology

1976-12-01

ATMOSPHERIC OPTICS DATA BASE Robert E. Roberts December 1976 Ott 𔃾 a IDA INSTITUTE FOR DEFENSE ANALYSES 𔃾 SCIENCE AND TECHNOLOGY DIVISION 400 Army-Navy...distribu- tions, including three haze models and three cloud models, are shown in Fig. 2 for 0.7 pim and 10 um radiation. As one proceeds from the various...7 10 0.1 0.2 0.3 0.4 0.5 0.6 0.1 0.8 0.9 1.0 TRANSMISSION (8. 1-12.0 MICRONS) F.3’IGURE A-i1. Transmission in the 3.4-4.1 pim and 0.8-1.1 umn Bands

Thermal Shock and Oxidation Behavior of HiPIMS TiAlN Coatings Grown on Ti-48Al-2Cr-2Nb Intermetallic Alloy

PubMed Central

Badini, Claudio; Deambrosis, Silvia M.; Padovano, Elisa; Fabrizio, Monica; Ostrovskaya, Oxana; Miorin, Enrico; D’Amico, Giuseppe C.; Montagner, Francesco; Biamino, Sara; Zin, Valentina

2016-01-01

A High Power Impulse Magnetron Sputtering (HiPIMS) method for depositing TiAlN environmental barrier coatings on the surface of Ti-48Al-2Cr-2Nb alloy was developed in view of their exploitation in turbine engines. Three differently engineered TiAlN films were processed and their performance compared. Bare intermetallic alloy coupons and coated specimens were submitted to thermal cycling under oxidizing atmosphere up to 850 °C or 950 °C, at high heating and cooling rates. For this purpose, a burner rig able to simulate the operating conditions of the different stages of turbine engines was used. Microstructures of the samples were compared before and after each test using several techniques (microscopy, XRD, and XPS). Coating-intermetallic substrate adhesion and tribological properties were investigated too. All the TiAlN films provided a remarkable increase in oxidation resistance. Good adhesion properties were observed even after repeated thermal shocks. HiPIMS pretreatments of the substrate surfaces performed before the coating deposition significantly affected the oxidation rate, the oxide layer composition and the coating/substrate adhesion. PMID:28774082

Highly conductive ultrathin Co films by high-power impulse magnetron sputtering

NASA Astrophysics Data System (ADS)

Jablonka, L.; Riekehr, L.; Zhang, Z.; Zhang, S.-L.; Kubart, T.

2018-01-01

Ultrathin Co films deposited on SiO2 with conductivities exceeding that of Cu are demonstrated. Ionized deposition implemented by high-power impulse magnetron sputtering (HiPIMS) is shown to result in smooth films with large grains and low resistivities, namely, 14 µΩ cm at a thickness of 40 nm, which is close to the bulk value of Co. Even at a thickness of only 6 nm, a resistivity of 35 µΩ cm is obtained. The improved film quality is attributed to a higher nucleation density in the Co-ion dominated plasma in HiPIMS. In particular, the pulsed nature of the Co flux as well as shallow ion implantation of Co into SiO2 can increase the nucleation density. Adatom diffusion is further enhanced in the ionized process, resulting in a dense microstructure. These results are in contrast to Co deposited by conventional direct current magnetron sputtering where the conductivity is reduced due to smaller grains, voids, rougher interfaces, and Ar incorporation. The resistivity of the HiPIMS films is shown to be in accordance with models by Mayadas-Shatzkes and Sondheimer which consider grain-boundary and surface-scattering.

Comparison between Palm Oil Derivative and Commercial Thermo-Plastic Binder System on the Properties of the Stainless Steel 316L Sintered Parts

NASA Astrophysics Data System (ADS)

Ibrahim, R.; Azmirruddin, M.; Wei, G. C.; Fong, L. K.; Abdullah, N. I.; Omar, K.; Muhamad, M.; Muhamad, S.

2010-03-01

Binder system is one of the most important criteria for the powder injection molding (PIM) process. Failure in the selection of the binder system will affect on the final properties of the sintered parts. The objectives of this studied is to develop a novel binder system based on the local natural resources and environmental friendly binder system from palm oil derivative which is easily available and cheap in our country of Malaysia. The novel binder that has been developed will be replaced the commercial thermo-plastic binder system or as an alternative binder system. The results show that the physical and mechanical properties of the final sintered parts fulfill the Metal Powder Industries Federation (MPIF) standard 35 for PIM parts. The biocompatibility test using cell osteosarcoma (MG63) and vero fibroblastic also shows that the cell was successfully growth on the sintered stainless steel 316L parts indicate that the novel binder was not toxic. Therefore, the novel binder system based on palm oil derivative that has been developed as a binder system fulfills the important criteria for the binder system in PIM process.

Rehabilitation after amputation: psychotherapeutic intervention module in Indian scenario.

PubMed

Srivastava, Kalpana; Chaudhury, Suprakash

2014-01-01

Psychological aspects of adjustment to amputation are varied and not addressed in the present treatment regime. There is no research evidence available of psychological intervention and outcome in Indian scenario. One hundred and seventy-three consecutive patients with limb amputations were randomly assigned to psychotherapeutic intervention module (PIM, study group) (n = 90) and treatment as usual group (TAU, control group) (n = 83). Patients with psychotic disorder were excluded from the study. Carroll Rating Scale for Depression (CRSD), State-Trait Anxiety Inventory (STAI), Amputees Body Image Scale (ABIS), and Impact of Event Scale (IES) along with specially designed information schedule were administered individually. Structured psychotherapeutic module was developed for the intervention. Patients in PIM group were given six therapy sessions, addressing the specific areas of concern. All patients were evaluated on the same tools after two months of therapy. Analysis showed that after treatment a significant reduction in scores was noted on CRSD, STAI, ABIS, and IES in the PIM group. On the TAU group a significant reduction was seen only in the ABIS. The psychological intervention module proposed by authors was efficacious in alleviating the psychological distress, depression, and anxiety and thus was vastly superior to the conventional method of management of amputees.

Time-resolved multi-mass ion imaging: Femtosecond UV-VUV pump-probe spectroscopy with the PImMS camera.

PubMed

Forbes, Ruaridh; Makhija, Varun; Veyrinas, Kévin; Stolow, Albert; Lee, Jason W L; Burt, Michael; Brouard, Mark; Vallance, Claire; Wilkinson, Iain; Lausten, Rune; Hockett, Paul

2017-07-07

The Pixel-Imaging Mass Spectrometry (PImMS) camera allows for 3D charged particle imaging measurements, in which the particle time-of-flight is recorded along with (x, y) position. Coupling the PImMS camera to an ultrafast pump-probe velocity-map imaging spectroscopy apparatus therefore provides a route to time-resolved multi-mass ion imaging, with both high count rates and large dynamic range, thus allowing for rapid measurements of complex photofragmentation dynamics. Furthermore, the use of vacuum ultraviolet wavelengths for the probe pulse allows for an enhanced observation window for the study of excited state molecular dynamics in small polyatomic molecules having relatively high ionization potentials. Herein, preliminary time-resolved multi-mass imaging results from C 2 F 3 I photolysis are presented. The experiments utilized femtosecond VUV and UV (160.8 nm and 267 nm) pump and probe laser pulses in order to demonstrate and explore this new time-resolved experimental ion imaging configuration. The data indicate the depth and power of this measurement modality, with a range of photofragments readily observed, and many indications of complex underlying wavepacket dynamics on the excited state(s) prepared.

Removal of toxic metal ions from landfill leachate by complementary sorption and transport across polymer inclusion membranes.

PubMed

Zawierucha, Iwona; Kozlowski, Cezary; Malina, Grzegorz

2013-10-01

In this study, performance of a lab-scale two-step treatment system was evaluated for removal of toxic metal ions from landfill leachate. The technology of polymer inclusion membranes (PIMs) was the first step, while the second step of the treatment system was based on sorption on impregnated resin. The PIMs were synthesized from cellulose triacetate as a support, macrocyclic compound i.e. alkyl derivative of resorcinarene as a ionic carrier and o-nitrophenyl pentyl ether as a plasticizer. The transport experiments through PIM were carried out in a permeation cell, in which the membrane film was tightly clamped between two cell compartments. The sorption tests were carried out using a column filled with a resin impregnated with resorcinarene derivative. The obtained results show the good performance with respect to the removal of heavy metals from landfill leachate with the overall removal efficiency of 99%, 88% and 55% for Pb(II), Cd(II) and Zn(II) ions, respectively. Moreover the contents of metal ions in the leachate sample after treatment system were below permissible limit for wastewater according to the Polish Standards. Copyright © 2012 Elsevier Ltd. All rights reserved.

Compendium of Information for Interpreting the Microgravity Environment of the Orbiter Spacecraft

NASA Technical Reports Server (NTRS)

DeLombard, Richard

1996-01-01

Science experiments are routinely conducted on the NASA shuttle orbiter vehicles. Primarily, these experiments are operated on such missions to take advantage of the microgravity (low-level acceleration) environment conditions during on-orbit operations. Supporting accelerometer instruments are operated with the experiments to measure the microgravity acceleration environment in which the science experiments were operated. Tne Principal Investigator Microgravity Services (PIMS) Project at NASA Lewis Research Center interprets these microgravity acceleration data and prepares mission summary reports to aid the principal investigators of the scientific experiments in understanding the microgravity environment. Much of the information about the orbiter vehicle and the microgravity environment remains the same for each mission. Rather than repeat that information in each mission summary report, reference information is presented in this report to assist users in understanding the microgravity-acceleration data. The characteristics of the microgravity acceleration environment are first presented. The methods of measurement and common instruments used on orbiter missions are described. The coordinate systems utilized in the orbiter and accelerometers are described. Some of the orbiter attitudes utilized in microgravity related missions are illustrated. Methods of data processing are described and illustrated. The interpretation of the microgravity acceleration data is included with an explanation of common disturbance sources. Instructions to access some of the acceleration data and a description of the orbiter thrusters are explained in the appendixes. A microgravity environment bibliography is also included.

Coherent perfect absorber and laser modes in purely imaginary metamaterials

NASA Astrophysics Data System (ADS)

Fu, Yangyang; Cao, Yanyan; Cummer, Steven A.; Xu, Yadong; Chen, Huanyang

2017-10-01

Conjugate metamaterials, in which the permittivity and the permeability are complex conjugates of each other, possess the elements of loss and gain simultaneously. By employing a conjugate metamaterial with a purely imaginary form, we propose a mechanism for realizing both coherent perfect absorber (CPA) and laser modes. Moreover, the general conditions for obtaining CPA and laser modes, including obtaining them simultaneously, are revealed by analyzing the wave scattering properties of a slab made of purely imaginary metamaterials (PIMs). Specifically, in a PIM slab with a subunity effective refractive index, the CPA mode can be simplified as a perfect absorption mode and the incident wave from one side could be perfectly absorbed.

Alfven's critical ionization velocity observed in high power impulse magnetron sputtering discharges

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

Brenning, N.; Lundin, D.

2012-09-15

Azimuthally rotating dense plasma structures, spokes, have recently been detected in several high power impulse magnetron sputtering (HiPIMS) devices used for thin film deposition and surface treatment, and are thought to be important for plasma buildup, energizing of electrons, as well as cross-B transport of charged particles. In this work, the drift velocities of these spokes are shown to be strongly correlated with the critical ionization velocity, CIV, proposed by Alfven. It is proposed as the most promising approach in combining the CIV and HiPIMS research fields is to focus on the role of spokes in the process of electronmore » energization.« less

Multipurpose active pixel sensor (APS)-based microtracker

NASA Astrophysics Data System (ADS)

Eisenman, Allan R.; Liebe, Carl C.; Zhu, David Q.

1998-12-01

A new, photon-sensitive, imaging array, the active pixel sensor (APS) has emerged as a competitor to the CCD imager for use in star and target trackers. The Jet Propulsion Laboratory (JPL) has undertaken a program to develop a new generation, highly integrated, APS-based, multipurpose tracker: the Programmable Intelligent Microtracker (PIM). The supporting hardware used in the PIM has been carefully selected to enhance the inherent advantages of the APS. Adequate computation power is included to perform star identification, star tracking, attitude determination, space docking, feature tracking, descent imaging for landing control, and target tracking capabilities. Its first version uses a JPL developed 256 X 256-pixel APS and an advanced 32-bit RISC microcontroller. By taking advantage of the unique features of the APS/microcontroller combination, the microtracker will achieve about an order-of-magnitude reduction in mass and power consumption compared to present state-of-the-art star trackers. It will also add the advantage of programmability to enable it to perform a variety of star, other celestial body, and target tracking tasks. The PIM is already proving the usefulness of its design concept for space applications. It is demonstrating the effectiveness of taking such an integrated approach in building a new generation of high performance, general purpose, tracking instruments to be applied to a large variety of future space missions.

Determination of effective loss factors in reduced SEA models

NASA Astrophysics Data System (ADS)

Chimeno Manguán, M.; Fernández de las Heras, M. J.; Roibás Millán, E.; Simón Hidalgo, F.

2017-01-01

The definition of Statistical Energy Analysis (SEA) models for large complex structures is highly conditioned by the classification of the structure elements into a set of coupled subsystems and the subsequent determination of the loss factors representing both the internal damping and the coupling between subsystems. The accurate definition of the complete system can lead to excessively large models as the size and complexity increases. This fact can also rise practical issues for the experimental determination of the loss factors. This work presents a formulation of reduced SEA models for incomplete systems defined by a set of effective loss factors. This reduced SEA model provides a feasible number of subsystems for the application of the Power Injection Method (PIM). For structures of high complexity, their components accessibility can be restricted, for instance internal equipments or panels. For these cases the use of PIM to carry out an experimental SEA analysis is not possible. New methods are presented for this case in combination with the reduced SEA models. These methods allow defining some of the model loss factors that could not be obtained through PIM. The methods are validated with a numerical analysis case and they are also applied to an actual spacecraft structure with accessibility restrictions: a solar wing in folded configuration.

Promotion effect of H2 on ethanol oxidation and NOx reduction with ethanol over Ag/Al2O3 catalyst.

PubMed

Yu, Yunbo; Li, Yi; Zhang, Xiuli; Deng, Hua; He, Hong; Li, Yuyang

2015-01-06

The catalytic partial oxidation of ethanol and selective catalytic reduction of NOx with ethanol (ethanol-SCR) over Ag/Al2O3 were studied using synchrotron vacuum ultraviolet (VUV) photoionization mass spectrometry (PIMS). The intermediates were identified by PIMS and their photoionization efficiency (PIE) spectra. The results indicate that H2 promotes the partial oxidation of ethanol to acetaldehyde over Ag/Al2O3, while the simultaneously occurring processes of dehydration and dehydrogenation were inhibited. H2 addition favors the formation of ammonia during ethanol-SCR over Ag/Al2O3, the occurrence of which creates an effective pathway for NOx reduction by direct reaction with NH3. Simultaneously, the enhancement of the formation of ammonia benefits its reaction with surface enolic species, resulting in producing -NCO species again, leading to enhancement of ethanol-SCR over Ag/Al2O3 by H2. Using VUV-PIMS, the reactive vinyloxy radical was observed in the gas phase during the NOx reduction by ethanol for the first time, particularly in the presence of H2. Identification of such a reaction occurring in the gas phase may be crucial for understanding the reaction pathway of HC-SCR over Ag/Al2O3.

A HiPIMS plasma source with a magnetic nozzle that accelerates ions: application in a thruster

NASA Astrophysics Data System (ADS)

Bathgate, Stephen N.; Ganesan, Rajesh; Bilek, Marcela M. M.; McKenzie, David R.

2017-01-01

We demonstrate a solid fuel electrodeless ion thruster that uses a magnetic nozzle to collimate and accelerate copper ions produced by a high power impulse magnetron sputtering discharge (HiPIMS). The discharge is initiated using argon gas but in a practical device the consumption of argon could be minimised by exploiting the self-sputtering of copper. The ion fluence produced by the HiPIMS discharge was measured with a retarding field energy analyzer (RFEA) as a function of the magnetic field strength of the nozzle. The ion fraction of the copper was determined from the deposition rate of copper as a function of substrate bias and was found to exceed 87%. The ion fluence and ion energy increased in proportion with the magnetic field of the nozzle and the energy of the ions was found to follow a Maxwell-Boltzmann distribution with a directed velocity. The effectiveness of the magnetic nozzle in converting the randomized thermal motion of the ions into a jet was demonstrated from the energy distribution of the ions. The maximum ion exhaust velocity of at least 15.1 km/s, equivalent to a specific impulse of 1543 s was measured which is comparable to existing Hall thrusters and exceeds that of Teflon pulsed plasma thrusters.

Synthesis of Pyridine and Spiropyridine Derivatives Derived from 2-aminoprop- 1-ene-1,1,3-tricarbonitrile Together with their c-Met Kinase and Antiproliferative Evaluations.

PubMed

Mohareb, Rafat M; Abouzied, Amr S; Abbas, Nermeen S

2018-02-07

Among a wide range of pyridines, 3-cyanopyridines acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the pyridine nucleus were known in the market. The aim of this work was to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. To achieve this goal, our strategy was to synthesize a series of 3-cyanopyridine derivatives using 2-aminoprop-1-ene-1,1,3-tricarbonitrile (1) as the key starting material for many heterocyclization reactions. Muticoponent reactions were adopted using compound 1 to get different pyridine derivatives that were capable for different heterocyclization reactions. Antiproliferative evaluations and c-Met kinase, Pim-1 kinse inhibitions were perform where some compounds gave high activities. Compounds that showed high antiprolifeative activity were tested gor c-Met-independent and the results showed that compounds 5c, 5e, 5f, 7c, 7f and 16d were more active than foretinib. The Pim-1 kinase inhibition activity of some selected compounds showed that compounds 5e and 16c were high potent to inhibit Pim-1 activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A novel polymer inclusion membrane based method for continuous clean-up of thiocyanate from gold mine tailings water.

PubMed

Cho, Youngsoo; Cattrall, Robert W; Kolev, Spas D

2018-01-05

Thiocyanate is present in gold mine tailings waters in concentrations up to 1000mgL -1 and this has a serious environmental impact by not allowing water reuse in the flotation of gold ore. This significantly increases the consumption of fresh water and the amount of wastewater discharged in tailings dams. At the same time thiocyanate in tailings waters often leads to groundwater contamination. A novel continuous membrane-based method for the complete clean-up of thiocyanate in concentrations as high as 1000mgL -1 from its aqueous solutions has been developed. It employs a flat sheet polymer inclusion membrane (PIM) of composition 70wt% PVC, 20wt% Aliquat 336 and 10wt% 1-tetradecanol which separates counter-current streams of a feed thiocyanate solution and a 1M NaNO 3 receiving solution. The PIM-based system has been operated continuously for 45days with 99% separation efficiency. The volume of the receiving solution has been drastically reduced by recirculating it and continuously removing thiocyanate by precipitating it with in-situ generated Cu(I). The newly developed PIM-based thiocyanate clean-up method is environmentally friendly in terms of reagent use and inexpensive with respect to both equipment and running costs. Copyright © 2017 Elsevier B.V. All rights reserved.

Low-energy ion irradiation in HiPIMS to enable anatase TiO2 selective growth

NASA Astrophysics Data System (ADS)

Cemin, Felipe; Tsukamoto, Makoto; Keraudy, Julien; Antunes, Vinícius Gabriel; Helmersson, Ulf; Alvarez, Fernando; Minea, Tiberiu; Lundin, Daniel

2018-06-01

High power impulse magnetron sputtering (HiPIMS) has already demonstrated great potential for synthesizing the high-energy crystalline phase of titanium dioxide (rutile TiO2) due to large quantities of highly energetic ions present in the discharge. In this work, it is shown that the metastable anatase phase can also be obtained by HiPIMS. The required deposition conditions have been identified by systematically studying the phase formation, microstructure and chemical composition as a function of mode of target operation as well as of substrate temperature, working pressure, and peak current density. It is found that films deposited in the metal and transition modes are predominantly amorphous and contain substoichiometric TiO x compounds, while in compound mode they are well-crystallized and present only O2‑ ions bound to Ti4+, i.e. pure TiO2. Anatase TiO2 films are obtained for working pressures between 1 and 2 Pa, a peak current density of ~1 A cm‑2 and deposition temperatures lower than 300 °C. Rutile is favored at lower pressures (<1 Pa) and higher peak current densities (>2 A cm‑2), while amorphous films are obtained at higher pressures (5 Pa). Microstructural characterization of selected films is also presented.

Combination of Pim kinase inhibitor, SGI-1776, with bendamustine in B-cell lymphoma

PubMed Central

Yang, Qingshan; Chen, Lisa S; Neelapu, Sattva S.; Gandhi, Varsha

2013-01-01

SGI-1776 is a small molecule Pim kinase inhibitor that primarily targets c-Myc-driven transcription and cap-dependent translation in mantle cell lymphoma (MCL) cells. Bendamustine is an alkylating chemotherapeutic agent approved for use in B-cell lymphoma that is known to induce DNA damage and to initiate response to repair. We hypothesized that while each drug leads to the effects as stated above, combination of these drugs will enhance SGI-1776-induced inhibition of global transcription and translation processes, while promoting bendamustine-triggered decrease of DNA synthesis and DNA damage response in B-cell lymphoma. Both SGI-1776 and bendamustine as single agents effectively induced apoptosis and when used in combination, additive effect in cell killing was observed in MCL cell lines, JeKo-1 and Mino, as well as MCL and splenic marginal zone lymphoma (a type of B-cell lymphoma) primary cells. As expected, SGI-1776 was effective in inducing decrease of global RNA and protein synthesis, while bendamustine significantly inhibited DNA synthesis and generated DNA damage response. When used in combination, effects were intensified in DNA, RNA and protein syntheses compared to single agent treatments. Together, these data provided foundation and suggested feasibility of using Pim kinase inhibitor in combination with chemotherapeutic agents such as bendamustine in B-cell lymphoma. PMID:24290221

Squamous intraepithelial lesions of the anal squamocolumnar junction: Histopathological classification and HPV genotyping.

PubMed

Clavero, Omar; McCloskey, Jenny; Molina, Vicente Marco; Quirós, Beatriz; Bravo, Ignacio G; de Sanjosé, Silvia; Bosch, F Xavier; Pimenoff, Ville N

2017-06-01

Human papillomavirus (HPV)-related anal cancer lesions are often found adjacent to the squamocolumnar junction (SCJ). We have assessed the histopathology and associated HPV genotypes in anal SCJ lesions in surgically excised anal warts in HIV-negative and -positive patients. Histopathology identified 47 squamous intraepithelial lesions (SILs) adjacent to the SCJ amongst a total of 145 cases of clinically diagnosed anal condylomata. The anal SCJ lesions were further analyzed with p16, CK7 and p63 immunohistochemistry and HPV genotyping. Sixteen (16/47) of the excised anal wart lesions contained HSIL; Three were HSIL and exclusively associated with oncogenic HPVs. A further thirteen (13/47) were mixed lesions. Of these eight were HSILs with LSIL and six were HSILs with papillary immature metaplasia (PIM); Ten of the mixed lesions were associated with one or more oncogenic HPVs, while three cases were exclusively associated with HPV6. Clinically diagnosed anal warts cannot be assumed to be limited to low-grade lesions as anal warts of the SCJ often show heterogeneous lesions, with coexistence of LSIL, PIM, and HSIL. Lesions showing PIM, however, may mimic HSIL, because they are hypercellular, but lack the nuclear atypia and conspicuous mitotic activity of HSIL; and are p16 negative. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Thickness Dependence of the Dzyaloshinskii-Moriya Interaction in Co2 FeAl Ultrathin Films: Effects of Annealing Temperature and Heavy-Metal Material

NASA Astrophysics Data System (ADS)

Belmeguenai, M.; Roussigné, Y.; Bouloussa, H.; Chérif, S. M.; Stashkevich, A.; Nasui, M.; Gabor, M. S.; Mora-Hernández, A.; Nicholson, B.; Inyang, O.-O.; Hindmarch, A. T.; Bouchenoire, L.

2018-04-01

The interfacial Dzyaloshinskii-Moriya interaction (IDMI) is investigated in Co2FeAl (CFA) ultrathin films of various thicknesses (0.8 nm ≤tCFA≤2 nm ) grown by sputtering on Si substrates, using Pt, W, Ir, and MgO buffer or/and capping layers. Vibrating sample magnetometry reveals that the magnetization at saturation (Ms ) for the Pt- and Ir-buffered films is higher than the usual Ms of CFA due to the proximity-induced magnetization (PIM) in Ir and Pt estimated to be 19% and 27%, respectively. The presence of PIM in these materials is confirmed using x-ray resonant magnetic reflectivity. Moreover, while no PIM is induced in W, higher PIM is obtained with Pt when it is used as a buffer layer rather than a capping layer. Brillouin light scattering in the Damon-Eshbach geometry is used to investigate the thickness dependences of the IDMI constants from the spin-wave nonreciprocity and the perpendicular anisotropy field versus the annealing temperature. The IDMI sign is found to be negative for Pt /CFA and Ir /CFA , while it is positive for W /CFA . The thickness dependence of the effective IDMI constant for stacks involving Pt and W shows the existence of two regimes similar to that of the perpendicular anisotropy constant due to the degradation of the interfaces as the CFA thickness approaches a critical thickness. The surface IDMI and anisotropy constants of each stack are determined for the thickest samples where a linear thickness dependence of the effective IDMI constant and the effective magnetization are observed. The interface anisotropy and IDMI constants investigated for the Pt /CFA /MgO system show different trends with the annealing temperature. The decrease of the IDMI constant with increasing annealing temperature is probably due to the electronic structure changes at the interfaces, while the increase of the interface anisotropy constant is coherent with the interface quality and disorder enhancement.

[On the Way to Culture-Sensitive Patient Information Materials: Results of a Focus Group Study].

PubMed

Ries, Zivile; Frank, Fabian; Bermejo, Isaac; Kalaitsidou, Chariklia; Zill, Jördis; Dirmaier, Jörg; Härter, Martin; Bengel, Jürgen; Hölzel, Lars

2018-06-01

This study was part of a double-blind randomised controlled trial aimed to evaluate the effects of culture-sensitive patient information materials (PIM) compared with standard translated material. The study aimed to obtain the data for the development of culture sensitive PIM about unipolar depression for the 4 largest migrant groups in Germany (Turkish, Polish, Russian and Italian migration background). A qualitative study using 4 manual-based focus groups (FG), one for each migrant group, with 29 participants (9 with a Turkish (TüG), 8 with a Polish (PoG), 5 with a Russian (RuG) and 7 with an Italian (ItG) migration background) was conducted. The discussions were recorded, transcribed and analyzed using qualitative content analysis. 7 categories were identified. For the (1.) development of a good culture-sensitive PIM an easy language, a clear structure, an assessable extent of information and the avoidance of stereotypes were highlighted cross-culturally in all four FG. RuG and PoG had the largest (2.) lack of information about the German health care system. Concerning the (3.) illness perception RuG named problems with recognizing and understanding depression. PoG, RuG and TüG thematized (4.) feared consequences of the illness and of professional helpseeking. ItG, PoG, RuG had fears concerning (5.) psychotropic drugs as a result from insufficient knowledge about medication. For (6.) doctor-patient relationship cultural specifics were identified in RuG and TüG and for (7.) migration or culture specific reasons for depression in RuG, ItG and TüG. Although the identified categories were relevant for all or for the majority of migrant groups, for most categories specific cultural aspects were discovered. These findings show the importance of a culture sensitive adaptation of PIM. © Georg Thieme Verlag KG Stuttgart · New York.

Influence of spokes on the ionized metal flux fraction in chromium high power impulse magnetron sputtering

NASA Astrophysics Data System (ADS)

Biskup, B.; Maszl, C.; Breilmann, W.; Held, J.; Böke, M.; Benedikt, J.; von Keudell, A.

2018-03-01

High power impulse magnetron sputtering (HiPIMS) discharges are an excellent tool for deposition of thin films with superior properties. By adjusting the plasma parameters, an energetic metal and reactive species growth flux can be controlled. This control requires, however, a quantitative knowledge of the ion-to-neutral ratio in the growth flux and of the ion energy distribution function to optimize the deposited energy per incorporated atom in the film. This quantification is performed by combining two diagnostics, a quartz crystal microbalance (QCM) combined with an ion-repelling grid system (IReGS) to discriminate ions versus neutrals and a HIDEN EQP plasma monitor to measure the ion energy distribution function (IEDF). This approach yields the ionized metal flux fraction (IMFF) as the ionization degree in the growth flux. This is correlated to the plasma performance recorded by time resolved ICCD camera measurements, which allow to identify the formation of pronounced ionization zones, so called spokes, in the HiPIMS plasma. Thereby an automatic technique was developed to identify the spoke mode number. The data indicates two distinct regimes with respect to spoke formation that occur with increasing peak power, a stochastic regime with no spokes at low peak powers followed by a regime with distinct spokes at varying mode numbers at higher peak powers. The IMFF increases with increasing peak power reaching values of almost 80% at very high peak powers. The transition in between the two regimes coincides with a pronounced change in the IMFF. This change indicates that the formation of spokes apparently counteracts the return effect in HiPIMS. Based on the IMFF and the mean energy of the ions, the energy per deposited atom together with the overall energy flux onto the substrate is calculated. This allows us to determine an optimum for the peak power density around 0.5 kW cm-2 for chromium HiPIMS.

Size distributions of coastal ocean suspended particulate inorganic matter: Amorphous silica and clay minerals and their dynamics

NASA Astrophysics Data System (ADS)

Zhang, Xiaodong; Stavn, Robert H.; Falster, Alexander U.; Rick, Johannes J.; Gray, Deric; Gould, Richard W.

2017-04-01

Particulate inorganic matter (PIM) is a key component in estuarine and coastal systems and plays a critical role in trace metal cycling. Better understanding of coastal dynamics and biogeochemistry requires improved quantification of PIM in terms of its concentration, size distribution, and mineral species composition. The angular pattern of light scattering contains detailed information about the size and composition of particles. These volume scattering functions (VSFs) were measured in Mobile Bay, Alabama, USA, a dynamic, PIM dominated coastal environment. From measured VSFs, we determined through inversion the particle size distributions (PSDs) of major components of PIM, amorphous silica and clay minerals. An innovation here is the extension of our reported PSDs significantly into the submicron range. The PSDs of autochthonous amorphous silica exhibit two unique features: a peak centered at about 0.8 μm between 0.2 and 4 μm and a very broad shoulder essentially extending from 4 μm to >100 μm. With an active and steady particle source from blooming diatoms, the shapes of amorphous silica PSDs for sizes <10 μm varied little across the study area, but showed more particles of sizes >10 μm inside the bay, likely due to wind-induced resuspension of larger frustules that have settled. Compared to autochthonous amorphous silica, the allochthonous clay minerals are denser and exhibit relatively narrower PSDs with peaks located between 1 and 4 μm. Preferential settling of larger mineral particles as well as the smaller but denser illite component further narrowed the size distributions of clay minerals as they were being transported outside the bay. The derived PSDs also indicated a very dynamic situation in Mobile Bay when a cold weather front passed through during the experiment. With northerly winds of speeds up to 15 m s-1, both amorphous silica and clay minerals showed a dramatic increase in concentration and broadening in size distribution outside the exit of the barrier islands, indicative of wind-induced resuspension and subsequent advection of particles out of Mobile Bay. While collectively recognized as the PIM, amorphous silica and clay minerals, as shown in this study, possess very different size distributions. Considering how differences in PSDs and the associated particle areas will effect differences in sorption/desorption properties of these components, the results also demonstrate the potential of applying VSF-inversion in studying biogeochemistry in the estuarine-coastal ocean system.

Data characterizing tensile behavior of cenosphere/HDPE syntactic foam.

PubMed

Kumar, B R Bharath; Doddamani, Mrityunjay; Zeltmann, Steven E; Gupta, Nikhil; Ramakrishna, Seeram

2016-03-01

The data set presented is related to the tensile behavior of cenosphere reinforced high density polyethylene syntactic foam composites "Processing of cenosphere/HDPE syntactic foams using an industrial scale polymer injection molding machine" (Bharath et al., 2016) [1]. The focus of the work is on determining the feasibility of using an industrial scale polymer injection molding (PIM) machine for fabricating syntactic foams. The fabricated syntactic foams are investigated for microstructure and tensile properties. The data presented in this article is related to optimization of the PIM process for syntactic foam manufacture, equations and procedures to develop theoretical estimates for properties of cenospheres, and microstructure of syntactic foams before and after failure. Included dataset contains values obtained from the theoretical model.

Data characterizing tensile behavior of cenosphere/HDPE syntactic foam

PubMed Central

Kumar, B.R. Bharath; Doddamani, Mrityunjay; Zeltmann, Steven E.; Gupta, Nikhil; Ramakrishna, Seeram

2016-01-01

The data set presented is related to the tensile behavior of cenosphere reinforced high density polyethylene syntactic foam composites “Processing of cenosphere/HDPE syntactic foams using an industrial scale polymer injection molding machine” (Bharath et al., 2016) [1]. The focus of the work is on determining the feasibility of using an industrial scale polymer injection molding (PIM) machine for fabricating syntactic foams. The fabricated syntactic foams are investigated for microstructure and tensile properties. The data presented in this article is related to optimization of the PIM process for syntactic foam manufacture, equations and procedures to develop theoretical estimates for properties of cenospheres, and microstructure of syntactic foams before and after failure. Included dataset contains values obtained from the theoretical model. PMID:26937472

Photo-physics study of a styrylquinoline as inhibitor of Pim-1 kinase: Solvent and concentration effects

NASA Astrophysics Data System (ADS)

Lamhasni, Taibi; Barbache, Sara; Ait Lyazidi, Saadia; Haddad, Mustapha; Hnach, Mohamed; Desmaële, Didier

2018-03-01

7-Nicotinoyl-styrylquinoline (MB96) displays an antiviral activity on HIV-1 infected CEM cell lines and is a promising inhibitor of the serine/threonine-protein Pim-1 kinase. By means of UV-vis spectroscopy supported by theoretical calculations this styrylquinoline is shown to exist in different conformations: the s-trans planar conformation along with other twisted ones with respect to the torsion around the single bond between the quinoline and the phenylethenyl appendage. Hydrogen bonding interactions with the solvent shift the skeleton of the MB96 towards the planar form, enhancing conjugation of π-electrons between the quinoline and the catechol parts, while self-association process seems furthering this planar conformation.

Initial Testing (Stage 1) of SGI-1776, a PIM1 Kinase Inhibitor, by the Pediatric Preclinical Testing Program

PubMed Central

Batra, Vandana; Maris, John M.; Kang, Min H.; Reynolds, C. Patrick; Houghton, Peter J.; Alexander, Denise; Kolb, E. Anders; Gorlick, Richard; Keir, Stephen T.; Carol, Hernan; Lock, Richard; Billups, Catherine A.; Smith, Malcolm A.

2011-01-01

The PIM kinase inhibitor, SGI-1776, was tested against the PPTP in vitro (1.0 nM to 10 μM) and in vivo panels (148 mg/kg daily x 5 days for 3 weeks). SGI-1776 exhibited cytotoxic activity in vitro with a median relative IC50 of 3.1 μM. SGI-1776 induced significant differences in EFS distribution in vivo in 9 of 31 solid tumor xenografts and in 1 of 8 of the evaluable ALL xenografts. SGI-1776 induced tumor growth inhibition meeting criteria for intermediate EFS T/C activity in 1 of 39 evaluable models. In contrast, SGI-1776 induced complete responses of subcutaneous MV4;11 (B myeloid leukemia). PMID:22052829

Understanding Determinants of Consumer Mobile Health Usage Intentions, Assimilation, and Channel Preferences

PubMed Central

Chen, Liwei; Pye, Jessica; Baird, Aaron

2013-01-01

Background Consumer use of mobile devices as health service delivery aids (mHealth) is growing, especially as smartphones become ubiquitous. However, questions remain as to how consumer traits, health perceptions, situational characteristics, and demographics may affect consumer mHealth usage intentions, assimilation, and channel preferences. Objective We examine how consumers’ personal innovativeness toward mobile services (PIMS), perceived health conditions, health care availability, health care utilization, demographics, and socioeconomic status affect their (1) mHealth usage intentions and extent of mHealth assimilation, and (2) preference for mHealth as a complement or substitute for in-person doctor visits. Methods Leveraging constructs from research in technology acceptance, technology assimilation, consumer behavior, and health informatics, we developed a cross-sectional online survey to study determinants of consumers’ mHealth usage intentions, assimilation, and channel preferences. Data were collected from 1132 nationally representative US consumers and analyzed by using moderated multivariate regressions and ANOVA. Results The results indicate that (1) 430 of 1132 consumers in our sample (37.99%) have started using mHealth, (2) a larger quantity of consumers are favorable to using mHealth as a complement to in-person doctor visits (758/1132, 66.96%) than as a substitute (532/1132, 47.00%), and (3) consumers’ PIMS and perceived health conditions have significant positive direct influences on mHealth usage intentions, assimilation, and channel preferences, and significant positive interactive influences on assimilation and channel preferences. The independent variables within the moderated regressions collectively explained 59.70% variance in mHealth usage intentions, 60.41% in mHealth assimilation, 34.29% in preference for complementary use of mHealth, and 45.30% in preference for substitutive use of mHealth. In a follow-up ANOVA examination, we found that those who were more favorable toward using mHealth as a substitute for in-person doctor visits than as a complement indicated stronger intentions to use mHealth (F 1,702=20.14, P<.001) and stronger assimilation of mHealth (F 1,702=41.866, P<.001). Conclusions Multiple predictors are shown to have significant associations with mHealth usage intentions, assimilation, and channel preferences. We suggest that future initiatives to promote mHealth should shift targeting of consumers from coarse demographics to nuanced considerations of individual dispositions toward mobile service innovations, complementary or substitutive channel use preferences, perceived health conditions, health services availability and utilization, demographics, and socioeconomic characteristics. PMID:23912839

Understanding determinants of consumer mobile health usage intentions, assimilation, and channel preferences.

PubMed

Rai, Arun; Chen, Liwei; Pye, Jessica; Baird, Aaron

2013-08-02

Consumer use of mobile devices as health service delivery aids (mHealth) is growing, especially as smartphones become ubiquitous. However, questions remain as to how consumer traits, health perceptions, situational characteristics, and demographics may affect consumer mHealth usage intentions, assimilation, and channel preferences. We examine how consumers' personal innovativeness toward mobile services (PIMS), perceived health conditions, health care availability, health care utilization, demographics, and socioeconomic status affect their (1) mHealth usage intentions and extent of mHealth assimilation, and (2) preference for mHealth as a complement or substitute for in-person doctor visits. Leveraging constructs from research in technology acceptance, technology assimilation, consumer behavior, and health informatics, we developed a cross-sectional online survey to study determinants of consumers' mHealth usage intentions, assimilation, and channel preferences. Data were collected from 1132 nationally representative US consumers and analyzed by using moderated multivariate regressions and ANOVA. The results indicate that (1) 430 of 1132 consumers in our sample (37.99%) have started using mHealth, (2) a larger quantity of consumers are favorable to using mHealth as a complement to in-person doctor visits (758/1132, 66.96%) than as a substitute (532/1132, 47.00%), and (3) consumers' PIMS and perceived health conditions have significant positive direct influences on mHealth usage intentions, assimilation, and channel preferences, and significant positive interactive influences on assimilation and channel preferences. The independent variables within the moderated regressions collectively explained 59.70% variance in mHealth usage intentions, 60.41% in mHealth assimilation, 34.29% in preference for complementary use of mHealth, and 45.30% in preference for substitutive use of mHealth. In a follow-up ANOVA examination, we found that those who were more favorable toward using mHealth as a substitute for in-person doctor visits than as a complement indicated stronger intentions to use mHealth (F₁,₇₀₂=20.14, P<.001) and stronger assimilation of mHealth (F₁,₇₀₂=41.866, P<.001). Multiple predictors are shown to have significant associations with mHealth usage intentions, assimilation, and channel preferences. We suggest that future initiatives to promote mHealth should shift targeting of consumers from coarse demographics to nuanced considerations of individual dispositions toward mobile service innovations, complementary or substitutive channel use preferences, perceived health conditions, health services availability and utilization, demographics, and socioeconomic characteristics.

Removal of phenol from aqueous solution using polymer inclusion membrane based on mixture of CTA and CA

NASA Astrophysics Data System (ADS)

Benosmane, Nadjib; Boutemeur, Baya; Hamdi, Safouane M.; Hamdi, Maamar

2018-03-01

Nowadays, there are increasingly stringent regulations requiring more and more treatment of industrial effluents to generate product waters which could be easily reused or disposed of to the environment without any harmful effects. In the present work, the removal of phenol from aqueous solution across polymer inclusion membrane (PIM), based on mixture of cellulose triacetate and cellulose acetate as support (75/25%), calix[4]resorcinarene derivative as a carrier and 2-nitrophenyl octyl ether (2-NPOE) as plasticizer was investigated. The experimental part of this investigation involved the influence of carrier nature, plasticizer concentration, pH phases, and phenol initial concentration on the removal efficiency of phenol from synthetic wastewater. A PIM containing 0.1 g (of mixture polymer), (0.15 g/g mixture of polymer) of carrier and (0.03 ml/g mixture of polymer) of 2-NPOE provided the highest percentage of phenol removal efficiency over a 6-day transport; the removal was found to be about 95%, indeed the removal was found to be highly dependent of pH phases. The feed solution in these transport experiments was at pH 2, while the stripping solution contained 0.20 M NaOH. This study claims that the PIM with a mixture of cellulose derivatives can be used effectively to remove phenols from wastewaters.

Polysulfide-Blocking Microporous Polymer Membrane Tailored for Hybrid Li-Sulfur Flow Batteries.

PubMed

Li, Changyi; Ward, Ashleigh L; Doris, Sean E; Pascal, Tod A; Prendergast, David; Helms, Brett A

2015-09-09

Redox flow batteries (RFBs) present unique opportunities for multi-hour electrochemical energy storage (EES) at low cost. Too often, the barrier for implementing them in large-scale EES is the unfettered migration of redox active species across the membrane, which shortens battery life and reduces Coulombic efficiency. To advance RFBs for reliable EES, a new paradigm for controlling membrane transport selectivity is needed. We show here that size- and ion-selective transport can be achieved using membranes fabricated from polymers of intrinsic microporosity (PIMs). As a proof-of-concept demonstration, a first-generation PIM membrane dramatically reduced polysulfide crossover (and shuttling at the anode) in lithium-sulfur batteries, even when sulfur cathodes were prepared as flowable energy-dense fluids. The design of our membrane platform was informed by molecular dynamics simulations of the solvated structures of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) vs lithiated polysulfides (Li2Sx, where x = 8, 6, and 4) in glyme-based electrolytes of different oligomer length. These simulations suggested polymer films with pore dimensions less than 1.2-1.7 nm might incur the desired ion-selectivity. Indeed, the polysulfide blocking ability of the PIM-1 membrane (∼0.8 nm pores) was improved 500-fold over mesoporous Celgard separators (∼17 nm pores). As a result, significantly improved battery performance was demonstrated, even in the absence of LiNO3 anode-protecting additives.

Cysteine desulfurase Nfs1 and Pim1 protease control levels of Isu, the Fe-S cluster biogenesis scaffold.

PubMed

Song, Ji-Yoon; Marszalek, Jaroslaw; Craig, Elizabeth Anne

2012-06-26

Fe-S clusters are critical prosthetic groups for proteins involved in various critical biological processes. Before being transferred to recipient apo-proteins, Fe-S clusters are assembled on the highly conserved scaffold protein Isu, the abundance of which is regulated posttranslationally on disruption of the cluster biogenesis system. Here we report that Isu is degraded by the Lon-type AAA+ ATPase protease of the mitochondrial matrix, Pim1. Nfs1, the cysteine desulfurase responsible for providing sulfur for cluster formation, is required for the increased Isu stability occurring after disruption of cluster formation on or transfer from Isu. Physical interaction between the Isu and Nfs1 proteins, not the enzymatic activity of Nfs1, is the important factor in increased stability. Analysis of several conditions revealed that high Isu levels can be advantageous or disadvantageous, depending on the physiological condition. During the stationary phase, elevated Isu levels were advantageous, resulting in prolonged chronological lifespan. On the other hand, under iron-limiting conditions, high Isu levels were deleterious. Compared with cells expressing normal levels of Isu, such cells grew poorly and exhibited reduced activity of the heme-containing enzyme ferric reductase. Our results suggest that modulation of the degradation of Isu by the Pim1 protease is a regulatory mechanism serving to rapidly help balance the cell's need for critical iron-requiring processes under changing environmental conditions.

Combination of Pim kinase inhibitor SGI-1776 and bendamustine in B-cell lymphoma.

PubMed

Yang, Qingshan; Chen, Lisa S; Neelapu, Sattva S; Gandhi, Varsha

2013-09-01

SGI-1776 is a small-molecule Pim kinase inhibitor that primarily targets c-MYC-driven transcription and cap-dependent translation in mantle cell lymphoma (MCL) cells. Bendamustine is an alkylating chemotherapeutic agent approved for use in B-cell lymphoma that is known to induce DNA damage and initiate response to repair. Our studies were conducted in MCL cell lines JeKo-1 and Mino, as well as primary B-cell lymphoma samples of MCL and splenic marginal zone lymphoma (SMZL), where we treated cells with SGI-1776 and bendamustine. We measured levels of cellular apoptosis, macromolecule synthesis inhibition, and DNA damage induced by drug treatments. Both SGI-1776 and bendamustine effectively induced apoptosis as single agents, and when used in combination, an additive effect in cell killing was observed in MCL cell lines JeKo-1 and Mino, as well as in MCL and SMZL primary cells. As expected, SGI-1776 was effective in inducing a decrease of global RNA and protein synthesis, and bendamustine significantly inhibited DNA synthesis and generated a DNA damage response. When used in combination, the effects were intensified in DNA, RNA, and protein synthesis inhibition compared with single-agent treatments. These data provide a foundation and suggest the feasibility of using Pim kinase inhibitors in combination with chemotherapeutic agents such as bendamustine in B-cell lymphoma. Copyright © 2013 Elsevier Inc. All rights reserved.

Oral microbiome and peri-implant diseases: where are we now?

PubMed Central

Pokrowiecki, Rafał; Mielczarek, Agnieszka; Zaręba, Tomasz; Tyski, Stefan

2017-01-01

Peri-implant infective diseases (PIIDs) in oral implantology are commonly known as peri-implant mucositis (PIM) and periimplantitis (PI). While PIM is restricted to the peri-implant mucosa and is reversible, PI also affects implant-supporting bone and, therefore, is very difficult to eradicate. PIIDs in clinical outcome may resemble gingivitis and periodontitis, as they share similar risk factors. However, recent study in the field of proteomics and other molecular studies indicate that PIIDs exhibit significant differences when compared to periodontal diseases. This review aims to elucidate the current knowledge of PIIDs, their etiopathology and diversified microbiology as well as the role of molecular studies, which may be a key to personalized diagnostic and treatment protocols of peri-implant infections in the near future. PMID:29238198

A model of evaluation planning, implementation and management: Toward a ?culture of information? within organizations

NASA Astrophysics Data System (ADS)

Bhola, H. S.

1992-03-01

The argument underlying the ongoing "paradigm shift" from logical positivism to constructionism is briefly laid out. A model of evaluation planning, implementation and management (called the P-I-M Model, for short) is then presented that assumes a complementarity between the two paradigms. The model further implies that for effective decision-making within human organizations, both "evaluative data" and "descriptive data" are needed. "Evaluative data" generated by evaluation studies must, therefore, be undergirded by an appropriate management information system (MIS) that can generate "descriptive data", concurrently with the process of program implementation. The P-I-M Model, if fully actualized, will enable human organizations to become vibrant "cultures of information" where "informed" decision-making becomes a shared norm among all stakeholders.

Initial testing (stage 1) of SGI-1776, a PIM1 kinase inhibitor, by the pediatric preclinical testing program.

PubMed

Batra, Vandana; Maris, John M; Kang, Min H; Reynolds, C Patrick; Houghton, Peter J; Alexander, Denise; Kolb, E Anders; Gorlick, Richard; Keir, Stephen T; Carol, Hernan; Lock, Richard; Billups, Catherine A; Smith, Malcolm A

2012-10-01

The PIM kinase inhibitor, SGI-1776, was tested against the PPTP in vitro (1.0 nM-10 µM) and in vivo panels (148 mg/kg daily × 5 days for 3 weeks). SGI-1776 exhibited cytotoxic activity in vitro with a median relative IC(50) of 3.1 µM. SGI-1776 induced significant differences in EFS distribution in vivo in 9 of 31 solid tumor xenografts and in 1 of 8 of the evaluable ALL xenografts. SGI-1776 induced tumor growth inhibition meeting criteria for intermediate EFS T/C activity in 1 of 39 evaluable models. In contrast, SGI-1776 induced complete responses of subcutaneous MV4;11 (B myeloid leukemia). Copyright © 2011 Wiley Periodicals, Inc.

The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.

PubMed

Whisenant, Thomas C; Peralta, Eigen R; Aarreberg, Lauren D; Gao, Nina J; Head, Steven R; Ordoukhanian, Phillip; Williamson, Jamie R; Salomon, Daniel R

2015-01-01

Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as "central" interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, "peripheral" interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation.

The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells

PubMed Central

Aarreberg, Lauren D.; Gao, Nina J.; Head, Steven R.; Ordoukhanian, Phillip; Williamson, Jamie R.; Salomon, Daniel R.

2015-01-01

Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as “central” interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, “peripheral” interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation. PMID:26641092

Retrospective evaluation of potentially inappropriate prescribing in hospitalized patients with renal impairment.

PubMed

Doody, Hannah K; Peterson, Gregory M; Watson, Danielle; Castelino, Ronald L

2015-03-01

Patients with chronic kidney disease require appropriate adjustment of nephrotoxic and renally cleared medications to ensure safe and effective pharmacotherapy. It is currently unclear how often appropriate medication selection and dosage adjustment occurs in practice. Therefore, this study aimed to evaluate the extent of potentially inappropriate prescribing (PIP) (the use of a contraindicated medication or inappropriately high dose according to the renal function) in patients with renal impairment from admission through to discharge from the Royal Hobart Hospital (RHH), Tasmania, Australia; to evaluate the medications most commonly implicated in PIP; and the factors associated with PIP in renal impairment. Medical records of 251 patients consecutively admitted to the RHH aged 40 years and above, with a creatinine clearance of ≤60 mL/min, and hypertension and/or diabetes mellitus in their medical history, were reviewed. PIP was assessed using the Australian Medicines Handbook and/or product information. Of the 251 patients, 81 (32.3%) were receiving a total of 116 potentially inappropriate medications (PIMs) at the time of admission. The number of patients receiving PIMs (81 vs. 44, p<0.001 chi-square test) as well as the total number of PIMs (116 vs. 63, p<0.001 Wilcoxon signed rank test) were significantly decreased at discharge. Metformin was the most common PIM at admission. However, PIP of metformin was reduced by approximately 50% by discharge. Logistic regression analysis revealed two significant independent risk factors for PIP: a higher number of medications at admission increased risk of PIP (OR 1.1, 95% CI 1.02-1.18, p=0.010), and higher initial estimated glomerular filtration rate (eGFR) decreased the risk of PIP (OR 0.9, 95% CI 0.96-0.99, p=0.011). Despite the limitations of lack of body weight documentation and lack of clear guidelines for dosage adjustment based on the eGFR, PIP in patients with renal impairment is common and admission to the hospital was associated with a significant reduction in PIP. More recognition of chronic kidney disease in the community and strategies to alert clinicians of the need for dosage adjustment in renal impairment are warranted.

Ultrastructural characterization of the pulmonary cellular defences in the lung of a bird, the rock dove, Columba livia

PubMed Central

Maina, J. N.; Cowley, H. M.

1998-01-01

Free (surface) avian respiratory macrophages (FARMs) were harvested by lavage of the lung/air-sac system of the rock dove, Columba livia. The presence of FARMs in the atria and infundibula was confirmed by scanning electron microscopy. The respiratory system has developed several cellular defence lines that include surface macrophages, epithelial, subepithelial and interstitial phagocytes, and pulmonary intravascular macrophages (PIMs). Hence, C. livia appears to have a multiple pulmonary cellular protective armoury. Ultrastructurally, the FARMs and the PIMs were similar to the corresponding cells of mammals. The purported high susceptibility of birds to respiratory diseases, a state that has largely been deduced from morbidities and mortalities of commercial birds, and which has chiefly been attributed to paucity of the FARMs, is not supported by the present observations.

A Realtime Active Feedback Control System For Coupled Nonlinear Chemical Oscillators

NASA Astrophysics Data System (ADS)

Tompkins, Nathan; Fraden, Seth

2012-02-01

We study the manipulation and control of oscillatory networks. As a model system we use an emulsion of Belousov-Zhabotinsky (BZ) oscillators packed on a hexagonal lattice. Each drop is observed and perturbed by a Programmable Illumination Microscope (PIM). The PIM allows us to track individual BZ oscillators, calculate the phase and order parameters of every drop, and selectively perturb specific drops with photo illumination, all in realtime. To date we have determined the native attractor patterns for drops in 1D arrays and 2D hexagonal packing as a function of coupling strength as well as determined methods to move the system from one attractor basin to another. Current work involves implementing these attractor control methods with our experimental system and future work will likely include implementing a model neural network for use with photo controllable BZ emulsions.

Polarization-interleave-multiplexed discrete multi-tone modulation with direct detection utilizing MIMO equalization.

PubMed

Zhou, Xian; Zhong, Kangping; Gao, Yuliang; Sui, Qi; Dong, Zhenghua; Yuan, Jinhui; Wang, Liang; Long, Keping; Lau, Alan Pak Tao; Lu, Chao

2015-04-06

Discrete multi-tone (DMT) modulation is an attractive modulation format for short-reach applications to achieve the best use of available channel bandwidth and signal noise ratio (SNR). In order to realize polarization-multiplexed DMT modulation with direct detection, we derive an analytical transmission model for dual polarizations with intensity modulation and direct diction (IM-DD) in this paper. Based on the model, we propose a novel polarization-interleave-multiplexed DMT modulation with direct diction (PIM-DMT-DD) transmission system, where the polarization de-multiplexing can be achieved by using a simple multiple-input-multiple-output (MIMO) equalizer and the transmission performance is optimized over two distinct received polarization states to eliminate the singularity issue of MIMO demultiplexing algorithms. The feasibility and effectiveness of the proposed PIM-DMT-DD system are investigated via theoretical analyses and simulation studies.

Perceived Maternal Behavioral Control, Infant Behavior, and Milk Supply: A Qualitative Study.

PubMed

Peacock-Chambers, Elizabeth; Dicks, Kaitlin; Sarathy, Leela; Brown, Allison A; Boynton-Jarrett, Renée

Disparities persist in breastfeeding exclusivity and duration despite increases in breastfeeding initiation. The objective of this study was to examine factors that influence maternal decision making surrounding infant feeding practices over time in a diverse inner-city population. We conducted a prospective qualitative study with 20 mothers recruited from 2 urban primary care clinics. Participants completed open-ended interviews and demographic questionnaires in English or Spanish administered at approximately 2 weeks and 6 months postpartum. Transcripts were analyzed using a combined technique of inductive (data-driven) and deductive (theory-driven, based on the Theory of Planned Behavior) thematic analysis using 3 independent coders and iterative discussion to reach consensus. All women initiated breastfeeding, and 65% reported perceived insufficient milk (PIM). An association between PIM and behavioral control emerged as the overarching theme impacting early breastfeeding cessation and evolved over time. Early postpartum, PIM evoked maternal distress-strong emotional responses to infant crying and need to control infant behaviors. Later, mothers accepted a perceived lack of control over milk supply with minimal distress or as a natural process. Decisions to stop breastfeeding occurred through an iterative process, informed by trials of various strategies and observations of subsequent changes in infant behavior, strongly influenced by competing psychosocial demands. Infant feeding decisions evolve over time and are influenced by perceptions of control over infant behavior and milk supply. Tailored anticipatory guidance is needed to provide time-sensitive strategies to cope with challenging infant behaviors and promote maternal agency over breastfeeding in low-income populations.

[Demonstrating that monitoring and punishing increase non-cooperative behavior in a social dilemma game].

PubMed

Kitakaji, Yoko; Ohnuma, Susumu

2014-04-01

This research demonstrated the negative influence of monitoring and punishing during a social dilemma game, taking the illegal dumping of industrial waste as an example. The first study manipulated three conditions: a producing-industries monitoring condition (PIM), an administrative monitoring condition (ADM), and a control condition (no monitoring). The results showed that non-cooperative behavior was more frequent in the PIM condition than in the control condition. The second study had three conditions: a punishing condition (PC), a monitoring condition (MC), and a control condition (no monitoring, no punishing). The results indicated that non-cooperative behavior was observed the most in the PC, and the least in the control condition. Furthermore, information regarding other players' costs and benefits was shared the most in the control conditions in both studies. The results suggest that sanctions prevent people from sharing information, which decreases expectations of mutual cooperation.

Integrated High-Speed Torque Control System for a Robotic Joint

NASA Technical Reports Server (NTRS)

Davis, Donald R. (Inventor); Radford, Nicolaus A. (Inventor); Permenter, Frank Noble (Inventor); Valvo, Michael C. (Inventor); Askew, R. Scott (Inventor)

2013-01-01

A control system for achieving high-speed torque for a joint of a robot includes a printed circuit board assembly (PCBA) having a collocated joint processor and high-speed communication bus. The PCBA may also include a power inverter module (PIM) and local sensor conditioning electronics (SCE) for processing sensor data from one or more motor position sensors. Torque control of a motor of the joint is provided via the PCBA as a high-speed torque loop. Each joint processor may be embedded within or collocated with the robotic joint being controlled. Collocation of the joint processor, PIM, and high-speed bus may increase noise immunity of the control system, and the localized processing of sensor data from the joint motor at the joint level may minimize bus cabling to and from each control node. The joint processor may include a field programmable gate array (FPGA).

Single crystal CVD diamond membranes for betavoltaic cells

NASA Astrophysics Data System (ADS)

Delfaure, C.; Pomorski, M.; de Sanoit, J.; Bergonzo, P.; Saada, S.

2016-06-01

A single crystal diamond large area thin membrane was assembled as a p-doped/Intrinsic/Metal (PIM) structure and used in a betavoltaic configuration. When tested with a 20 keV electron beam from a high resolution scanning electron microscope, we measured an open circuit voltage (Voc) of 1.85 V, a charge collection efficiency (CCE) of 98%, a fill-factor of 80%, and a total conversion efficiency of 9.4%. These parameters are inherently linked to the diamond membrane PIM structure that allows full device depletion even at 0 V and are among the highest reported up to now for any other material tested for betavoltaic devices. It enables to drive a high short-circuit current Isc up to 7.12 μA, to reach a maximum power Pmax of 10.48 μW, a remarkable value demonstrating the high-benefit of diamond for the realization of long-life radioisotope based micro-batteries.

Fabrication of robust tooling for mass production of polymeric microfluidic devices

NASA Astrophysics Data System (ADS)

Fu, G.; Tor, S. B.; Loh, N. H.; Hardt, D. E.

2010-08-01

Polymer microfluidic devices are gaining popularity for bio-applications. In both commonly used methods for the fabrication of polymer microfluidic devices, i.e. injection molding and hot-embossing, the quality of a mold insert is of high importance. Micro powder injection molding (μPIM) provides a suitable option for metal mold insert fabrication. In this paper, two mold inserts with micro-features of different patterns and sizes were produced using 316L stainless steel powder and an in-house binder system. The mold inserts were successfully used to produce cyclic olefin copolymer (COC, trade name TOPAS) micromixer plates with micro-channels of widths 100 µm and 50 µm. Compared with CNC-machined hot work steel mold inserts, the quality of the micro-channels is better as far as geometrical quality and dimensional tolerance are concerned. However, surface finish and flatness of the μPIM mold inserts are inferior to those of CNC-machined mold inserts.

Enhanced gas separation factors of microporous polymer constrained in the channels of anodic alumina membranes

PubMed Central

Chernova, Ekaterina; Petukhov, Dmitrii; Boytsova, Olga; Alentiev, Alexander; Budd, Peter; Yampolskii, Yuri; Eliseev, Andrei

2016-01-01

New composite membranes based on porous anodic alumina films and polymer of intrinsic microporosity (PIM-1) have been prepared using a spin-coating technique. According to scanning electron microscopy, partial penetration of polymer into the pores of alumina supports takes place giving rise to selective polymeric layers with fiber-like microstructure. Geometric confinement of rigid PIM-1 in the channels of anodic alumina causes reduction of small-scale mobility in polymeric chains. As a result, transport of permanent gases, such as CH4, becomes significantly hindered across composite membranes. Contrary, the transport of condensable gases (CO2, С4H10), did not significantly suffer from the confinement due to high solubility in the polymer matrix. This strategy enables enhancement of selectivity towards CO2 and C4H10 without significant loss of the membrane performance and seems to be prospective for drain and sweetening of natural gas. PMID:27498607

Personal Information Management for Nurses Returning to School.

PubMed

Bowman, Katherine

2015-12-01

Registered nurses with a diploma or an associate's degree are encouraged to return to school to earn a Bachelor of Science in Nursing degree. Until they return to school, many RNs have little need to regularly write, store, and retrieve work-related papers, but they are expected to complete the majority of assignments using a computer when in the student role. Personal information management (PIM) is a system of organizing and managing electronic information that will reduce computer clutter, while enhancing time use, task management, and productivity. This article introduces three PIM strategies for managing school work. Nesting is the creation of a system of folders to form a hierarchy for storing and retrieving electronic documents. Each folder, subfolder, and document must be given a meaningful unique name. Numbering is used to create different versions of the same paper, while preserving the original document. Copyright 2015, SLACK Incorporated.

First measurements of the temporal evolution of the plasma density in HiPIMS discharges using THz time domain spectroscopy

NASA Astrophysics Data System (ADS)

Meier, Steffen M.; Hecimovic, Ante; Tsankov, Tsanko V.; Luggenhölscher, Dirk; Czarnetzki, Uwe

2018-03-01

In this paper, the novel technique of THz time domain spectroscopy has been applied to obtain time-resolved measurements of the plasma density in the active zone of a HiPIMS discharge with a titanium target. The obtained peak values are in the range of 1012-1013 cm-3 for discharge current densities of 1-4 A cm-2 at 0.5 and 2 Pa argon pressure. The measured densities show good correlation with the discharge current and voltage and the intensity of various atomic and ionic lines. The well known phases of the discharge have been identified and related to the variation of the electron density. The measurement results show that the plasma density remains nearly constant during the runaway/self-sputtering phase. Based on that, it is conjectured that singly charged titanium ions are the dominant ion species during this phase.

Enhanced gas separation factors of microporous polymer constrained in the channels of anodic alumina membranes

NASA Astrophysics Data System (ADS)

Chernova, Ekaterina; Petukhov, Dmitrii; Boytsova, Olga; Alentiev, Alexander; Budd, Peter; Yampolskii, Yuri; Eliseev, Andrei

2016-08-01

New composite membranes based on porous anodic alumina films and polymer of intrinsic microporosity (PIM-1) have been prepared using a spin-coating technique. According to scanning electron microscopy, partial penetration of polymer into the pores of alumina supports takes place giving rise to selective polymeric layers with fiber-like microstructure. Geometric confinement of rigid PIM-1 in the channels of anodic alumina causes reduction of small-scale mobility in polymeric chains. As a result, transport of permanent gases, such as CH4, becomes significantly hindered across composite membranes. Contrary, the transport of condensable gases (CO2, С4H10), did not significantly suffer from the confinement due to high solubility in the polymer matrix. This strategy enables enhancement of selectivity towards CO2 and C4H10 without significant loss of the membrane performance and seems to be prospective for drain and sweetening of natural gas.

The origins and early elaboration of projectile technology.

PubMed

O'Driscoll, Corey A; Thompson, Jessica C

2018-01-01

The ability of Homo sapiens to kill prey at a distance is arguably one of the catalysts for our current ecological dominance. Many researchers have suggested its origins lie in the African Middle Stone Age or the European Middle Palaeolithic (∼300-30 thousand years ago), but the perishable components of armatures rarely preserve. Most research on this subject therefore emphasises analysis of armature tip size, shape, and diagnostic impacts or residues. Other lines of evidence have included human skeletal anatomy or analyses of the species composition of faunal assemblages. Projectile Impact Marks (PIMs) on archaeofaunal remains offer an ideal complement to this work, but their potential has been restricted mainly to the later Eurasian zooarchaeological record. A review of current evidence and approaches shows that systematic PIM research could add much to our understanding of early projectile technology, especially in Africa. © 2018 Wiley Periodicals, Inc.

The use of a polymer inclusion membrane in flow injection analysis for the on-line separation and determination of zinc.

PubMed

Zhang, Lujia L; Cattrall, Robert W; Kolev, Spas D

2011-06-15

This paper reports the first use of a polymer inclusion membrane (PIM) for on-line separation in flow injection analysis (FIA) involving simultaneous extraction and back-extraction. The FIA system containing the PIM separation module was used for the determination of Zn(II) in aqueous samples in the presence of Mg(II), Ca(II), Cd(II), Co(II), Ni(II), Cu(II), and Fe(III). The Fe(III) and Cu(II) interferences were eliminated by off-line precipitation with phosphate and on-line complexation with chloride, respectively. The concentration of Zn(II) was determined spectrophotometrically using 4-(2-pyridylazo) resorcinol (PAR). The optimal composition of the PIM consisted of 40% (m/m) di(2-ethlyhexyl) phosphoric acid (D2EHPA) as carrier, 10% (m/m) dioctyl phthalate (DOP) as plasticizer and 50% (m/m) poly(vinyl chloride) (PVC) as the base polymer. The optimized FIA system was characterized by a linear calibration curve in the range from 1.0 to 30.0 mg L(-1) Zn(II), a detection limit of 0.05 mg L(-1) and a relative standard deviation of 3.4% with a sampling rate of 4h(-1). Reproducible results were obtained for 20 replicate injections over a 5h period which demonstrated a good membrane stability. The FIA system was applied to the determination of Zn(II) in pharmaceuticals and samples from the galvanizing industry and very good agreement with atomic absorption spectrometry was obtained. Copyright © 2011 Elsevier B.V. All rights reserved.

A multiplex cytokine score for the prediction of disease severity in pediatric hematology/oncology patients with septic shock.

PubMed

Xu, Xiao-Jun; Tang, Yong-Min; Song, Hua; Yang, Shi-Long; Xu, Wei-Qun; Shi, Shu-Wen; Zhao, Ning; Liao, Chan

2013-11-01

Although many inflammatory cytokines are prognostic in sepsis, the utility of cytokines in evaluating disease severity in pediatric hematology/oncology patients with septic shock was rarely studied. On the other hand, a single particular cytokine is far from ideal in guiding therapeutic intervention, but combination of multiple biomarkers improves the accuracy. In this prospective observational study, 111 episodes of septic shock in pediatric hematology/oncology patients were enrolled from 2006 through 2012. Blood samples were taken for inflammatory cytokine measurement by cytometric bead array (CBA) technology at the initial onset of septic shock. Interleukin (IL)-6 and IL-10 were significantly elevated in majority of patients, while tumor necrosis factor (TNF)-α and interferon (IFN)-γ were markedly increased in patients with high pediatric index of mortality 2 (PIM2) score and non-survivors. All the four cytokines paralleled the PIM2 score and differentially correlated with hemodynamic disorder and fatal outcomes. The pediatric multiplex cytokine score (PMCS), which integrated the four cytokines into one score system, was related to hemodynamic disorder and mortality as well, but showed more powerful prediction ability than each of the four cytokines. PMCS was an independent predictive factor for fatal outcome, presenting similar discriminative power with PIM2, with accuracy of 0.83 (95% CI, 0.71-0.94). In conclusion, this study develops a cytokine scoring system based on CBA technique, which performs well in disease severity and fatality prediction in pediatric hematology/oncology patients with septic shock. Copyright © 2013 Elsevier Ltd. All rights reserved.

E-learning in order to improve drug prescription for hospitalized older patients: a cluster-randomized controlled study.

PubMed

Franchi, Carlotta; Tettamanti, Mauro; Djade, Codjo Dgnefa; Pasina, Luca; Mannucci, Pier Mannuccio; Onder, Graziano; Gussoni, Gualberto; Manfellotto, Dario; Bonassi, Stefano; Salerno, Francesco; Nobili, Alessandro

2016-07-01

The aim of the study was to evaluate the effect of an e-learning educational program meant to foster the quality of drug prescription in hospitalized elderly patients. Twenty geriatric and internal medicine wards were randomized to intervention (e-learning educational program) or control (basic geriatric pharmacology notions). Logistic regression analysis was used in order to assess the effect of the intervention on the use of potentially inappropriate medication (PIM, primary outcome) at hospital discharge. Secondary outcomes were a reduced prevalence of at least one potential drug-drug interaction (DDI) and potentially severe DDI at discharge. Mortality rate and incidence of re-hospitalizations were other secondary outcomes assessed at the 12-month follow-up. A total of 697 patients (347 in the intervention and 350 in the control arms) were enrolled. No difference in the prevalence of PIM at discharge was found between arms (OR 1.29 95%CI 0.87-1.91). We also found no decrease in the prevalence of DDI (OR 0.67 95%CI 0.34-1.28) and potentially severe DDI (OR 0.86 95%CI 0.63-1.15) at discharge, nor in mortality rates and incidence of re-hospitalization at 12-month follow-up. This e-learning educational program had no clear effect on the quality of drug prescription and clinical outcomes in hospitalized elderly patients. Given the high prevalence of PIMs and potential DDIs recorded in the frame of this study, other approaches should be developed in order to improve the quality of drug prescription in this population. © 2016 The British Pharmacological Society.

Scaling to Nanotechnology Limits with the PIMS Computer Architecture and a new Scaling Rule

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

Debenedictis, Erik P.

2015-02-01

We describe a new approach to computing that moves towards the limits of nanotechnology using a newly formulated sc aling rule. This is in contrast to the current computer industry scali ng away from von Neumann's original computer at the rate of Moore's Law. We extend Moore's Law to 3D, which l eads generally to architectures that integrate logic and memory. To keep pow er dissipation cons tant through a 2D surface of the 3D structure requires using adiabatic principles. We call our newly proposed architecture Processor In Memory and Storage (PIMS). We propose a new computational model that integratesmore » processing and memory into "tiles" that comprise logic, memory/storage, and communications functions. Since the programming model will be relatively stable as a system scales, programs repr esented by tiles could be executed in a PIMS system built with today's technology or could become the "schematic diagram" for implementation in an ultimate 3D nanotechnology of the future. We build a systems software approach that offers advantages over and above the technological and arch itectural advantages. Firs t, the algorithms may be more efficient in the conventional sens e of having fewer steps. Second, the algorithms may run with higher power efficiency per operation by being a better match for the adiabatic scaling ru le. The performance analysis based on demonstrated ideas in physical science suggests 80,000 x improvement in cost per operation for the (arguably) gene ral purpose function of emulating neurons in Deep Learning.« less

PIMS:Remediation of Soil and Groundwater Contaminated With Metals

DTIC Science & Technology

2006-06-01

24 4.4.1.1 Bioremediation/ Phytoremediation ...........................................24 4.4.1.2 Physical...ii 5.3.2 Grouting and Off-Site Disposal .................................................................31 5.3.3 Phytoremediation ...Above Background in Sieved Soil ...................................... 12 Table 3. Leachate Monitoring Results

Organic and Inorganic Matter in Louisiana Coastal Waters: Vermilion, Atchafalaya, Terrebonne, Barataria, and Mississippi Regions.

EPA Science Inventory

Chromophoric dissolved organic matter (CDOM) spectral absorption, dissolved organic carbon (DOC) concentration, and the particulate fraction of inorganic (PIM) and organic matter (POM) were measured in Louisiana coastal waters at Vermilion, Atchafalaya, Terrebonne, Barataria, and...

Optimization Review, Peck Iron and Metal Superfund Site, Portsmouth, Virginia

EPA Pesticide Factsheets

The Peck Iron and Metal Superfund Site is a 33-acre property located in Norfolk County, Portsmouth, Virginia. PIM (Figure 1) is the site of a former scrap metal storage and recycling facility that began operation in the 1940s.

Synchronization Dynamics of Coupled Chemical Oscillators

NASA Astrophysics Data System (ADS)

Tompkins, Nathan

The synchronization dynamics of complex networks have been extensively studied over the past few decades due to their ubiquity in the natural world. Prominent examples include cardiac rhythms, circadian rhythms, the flashing of fireflies, predator/prey population dynamics, mammalian gait, human applause, pendulum clocks, the electrical grid, and of the course the brain. Detailed experiments have been done to map the topology of many of these systems and significant advances have been made to describe the mathematics of these networks. Compared to these bodies of work relatively little has been done to directly test the role of topology in the synchronization dynamics of coupled oscillators. This Dissertation develops technology to examine the dynamics due to topology within networks of discrete oscillatory components. The oscillatory system used here consists of the photo-inhibitable Belousov-Zhabotinsky (BZ) reaction water-in-oil emulsion where the oscillatory drops are diffusively coupled to one another and the topology is defined by the geometry of the diffusive connections. Ring networks are created from a close-packed 2D array of drops using the Programmable Illumination Microscope (PIM) in order to test Turing's theory of morphogenesis directly. Further technology is developed to create custom planar networks of BZ drops in more complicated topologies which can be individually perturbed using illumination from the PIM. The work presented here establishes the validity of using the BZ emulsion system with a PIM to study the topology induced effects on the synchronization dynamics of coupled chemical oscillators, tests the successes and limitations of Turing's theory of morphogenesis, and develops new technology to further probe the effects of network topology on a system of coupled oscillators. Finally, this Dissertation concludes by describing ongoing experiments which utilize this new technology to examine topology induced transitions of synchronization dynamics of diffusively coupled chemical oscillators.

Can health indicators help policy-makers? Experience from European system of urban health indicators (EURO-URHIS).

PubMed

Torun, Perihan; Heller, Richard F; Harrison, Annie; Verma, Arpana

2017-05-01

This paper proposes that Population Impact Measures (PIMs), the Population Impact Number of Eliminating a Risk Factor over a time period (PIN-ER-t) and the number of events prevented in your population (NEPP), can assist in policy making as they include relevant information which describes the impact or benefits to the population of risk factors and interventions. In this study, we explore the utilization of the indicators from European System of Urban Health Indicators System to produce the two PIMs. We identified from the indicators list the health determinants, health status and health interventions which can be linked, and searched Medline for evidence of association. We then investigated whether the type of frequency measure available for the indicator match with the measure used in PIMs, and explored data availability for the City of Manchester (UK) as an urban area. Of the 39 indicators relevant to socio-economic factors, health determinants and health status, it was possible to calculate the population impact of a risk factor, i.e. the PIN-ER-t, for only six associations, and the population impact of health interventions, i.e. NEPP, for only one out of the three listed indicators, as the relevant health conditions were not included. The results of this study suggest that if an indicator system is intended to play a part in the policy making process, then the method of presentation to policy-makers should be decided before setting up the system, as it is likely that some indicators which would be essential might not be available. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

The thermal decomposition of the benzyl radical in a heated micro-reactor. I. Experimental findings

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

Buckingham, Grant T.; Ormond, Thomas K.; National Renewable Energy Laboratory, 15013 Denver West Parkway, Golden, Colorado 80401

2015-01-28

The pyrolysis of the benzyl radical has been studied in a set of heated micro-reactors. A combination of photoionization mass spectrometry (PIMS) and matrix isolation infrared (IR) spectroscopy has been used to identify the decomposition products. Both benzyl bromide and ethyl benzene have been used as precursors of the parent species, C{sub 6}H{sub 5}CH{sub 2}, as well as a set of isotopically labeled radicals: C{sub 6}H{sub 5}CD{sub 2}, C{sub 6}D{sub 5}CH{sub 2}, and C{sub 6}H{sub 5}{sup 13}CH{sub 2}. The combination of PIMS and IR spectroscopy has been used to identify the earliest pyrolysis products from benzyl radical as: C{sub 5}H{submore » 4}=C=CH{sub 2}, H atom, C{sub 5}H{sub 4}—C ≡ CH, C{sub 5}H{sub 5}, HCCCH{sub 2}, and HC ≡ CH. Pyrolysis of the C{sub 6}H{sub 5}CD{sub 2}, C{sub 6}D{sub 5}CH{sub 2}, and C{sub 6}H{sub 5}{sup 13}CH{sub 2} benzyl radicals produces a set of methyl radicals, cyclopentadienyl radicals, and benzynes that are not predicted by a fulvenallene pathway. Explicit PIMS searches for the cycloheptatrienyl radical were unsuccessful, there is no evidence for the isomerization of benzyl and cycloheptatrienyl radicals: C{sub 6}H{sub 5}CH{sub 2}⇋C{sub 7}H{sub 7}. These labeling studies suggest that there must be other thermal decomposition routes for the C{sub 6}H{sub 5}CH{sub 2} radical that differ from the fulvenallene pathway.« less

E‐learning in order to improve drug prescription for hospitalized older patients: a cluster‐randomized controlled study

PubMed Central

Tettamanti, Mauro; Djade, Codjo Dgnefa; Pasina, Luca; Mannucci, Pier Mannuccio; Onder, Graziano; Gussoni, Gualberto; Manfellotto, Dario; Bonassi, Stefano; Salerno, Francesco; Nobili, Alessandro

2016-01-01

Aims The aim of the study was to evaluate the effect of an e‐learning educational program meant to foster the quality of drug prescription in hospitalized elderly patients. Methods Twenty geriatric and internal medicine wards were randomized to intervention (e‐learning educational program) or control (basic geriatric pharmacology notions). Logistic regression analysis was used in order to assess the effect of the intervention on the use of potentially inappropriate medication (PIM, primary outcome) at hospital discharge. Secondary outcomes were a reduced prevalence of at least one potential drug–drug interaction (DDI) and potentially severe DDI at discharge. Mortality rate and incidence of re‐hospitalizations were other secondary outcomes assessed at the 12‐month follow‐up. Results A total of 697 patients (347 in the intervention and 350 in the control arms) were enrolled. No difference in the prevalence of PIM at discharge was found between arms (OR 1.29 95%CI 0.87–1.91). We also found no decrease in the prevalence of DDI (OR 0.67 95%CI 0.34–1.28) and potentially severe DDI (OR 0.86 95%CI 0.63–1.15) at discharge, nor in mortality rates and incidence of re‐hospitalization at 12‐month follow‐up. Conclusions This e‐learning educational program had no clear effect on the quality of drug prescription and clinical outcomes in hospitalized elderly patients. Given the high prevalence of PIMs and potential DDIs recorded in the frame of this study, other approaches should be developed in order to improve the quality of drug prescription in this population. PMID:26922904

Antibody purification-independent microarrays (PIM) by direct bacteria spotting on TiO2-treated slides.

PubMed

De Marni, Marzia L; Monegal, Ana; Venturini, Samuele; Vinati, Simone; Carbone, Roberta; de Marco, Ario

2012-02-01

The preparation of effective conventional antibody microarrays depends on the availability of high quality material and on the correct accessibility of the antibody active moieties following their immobilization on the support slide. We show that spotting bacteria that expose recombinant antibodies on their external surface directly on nanostructured-TiO(2) or epoxy slides (purification-independent microarray - PIM) is a simple and reliable alternative for preparing sensitive and specific microarrays for antigen detection. Variable domains of single heavy-chain antibodies (VHHs) against fibroblast growth factor receptor 1 (FGFR1) were used to capture the antigen diluted in serum or BSA solution. The FGFR1 detection was performed by either direct antigen labeling or using a sandwich system in which FGFR1 was first bound to its antibody and successively identified using a labeled FGF. In both cases the signal distribution within each spot was uniform and spot morphology regular. The signal-to-noise ratio of the signal was extremely elevated and the specificity of the system was proved statistically. The LOD of the system for the antigen was calculated being 0.4ng/mL and the dynamic range between 0.4ng/mL and 10μg/mL. The microarrays prepared with bacteria exposing antibodies remain fully functional for at least 31 days after spotting. We finally demonstrated that the method is suitable for other antigen-antibody pairs and expect that it could be easily adapted to further applications such as the display of scFv and IgG antibodies or the autoantibody detection using protein PIMs. Copyright © 2011. Published by Elsevier Inc.

Isolation of mtpim Proves Tnt1 a Useful Reverse Genetics Tool in Medicago truncatula and Uncovers New Aspects of AP1-Like Functions in Legumes1

PubMed Central

Benlloch, Reyes; d'Erfurth, Isabelle; Ferrandiz, Cristina; Cosson, Viviane; Beltrán, José Pío; Cañas, Luis Antonio; Kondorosi, Adam; Madueño, Francisco; Ratet, Pascal

2006-01-01

Comparative studies help shed light on how the huge diversity in plant forms found in nature has been produced. We use legume species to study developmental differences in inflorescence architecture and flower ontogeny with classical models such as Arabidopsis thaliana or Antirrhinum majus. Whereas genetic control of these processes has been analyzed mostly in pea (Pisum sativum), Medicago truncatula is emerging as a promising alternative system for these studies due to the availability of a range of genetic tools. To assess the use of the retrotransposon Tnt1 for reverse genetics in M. truncatula, we screened a small Tnt1-mutagenized population using degenerate primers for MADS-box genes, known controllers of plant development. We describe here the characterization of mtpim, a new mutant caused by the insertion of Tnt1 in a homolog to the PROLIFERATING INFLORESCENCE MERISTEM (PIM)/APETALA1 (AP1)/SQUAMOSA genes. mtpim shows flower-to-inflorescence conversion and altered flowers with sepals transformed into leaves, indicating that MtPIM controls floral meristem identity and flower development. Although more extreme, this phenotype resembles the pea pim mutants, supporting the idea that M. truncatula could be used to complement analysis of reproductive development already initiated in pea. In fact, our study reveals aspects not shown by analysis of pea mutants: that the mutation in the AP1 homolog interferes with the specification of floral organs from common primordia and causes conversion of sepals into leaves, in addition to true conversion of flowers into inflorescences. The isolation of mtpim represents a proof of concept demonstrating that Tnt1 populations can be efficiently used in reverse genetics screenings in M. truncatula. PMID:16963524

Denial of risk: The effects of positive impression management on risk assessments for psychopathic and nonpsychopathic offenders.

PubMed

Gillard, Nathan D; Rogers, Richard

2015-01-01

Risk assessments for offenders often combine past records with current clinical findings from observations, interviews, and test data. Conclusions based on these risk assessments are highly consequential, sometimes resulting in increased criminal sentences or prolonged hospitalization. Therefore, many offenders are motivated to intentionally minimize risk factors and their negative consequences. Positive impression management (PIM) is especially likely to occur in offenders with high psychopathic traits because goal-directed deception is reflected in several of psychopathy's core traits of the disorder, such as manipulativeness, glibness, and superficial charm. However, this connection appears to be based on the conceptual understanding of psychopathy, and has rarely been examined empirically for either frequency of or success at deception. The current study examined the ability of a jail sample to intentionally minimize risk factors and related criminal attributes using a repeated measures, simulation design. In general, offenders were able to effectively use PIM to lower scores on the HCR-20 and the Self-Appraisal Questionnaire (SAQ), while the Psychological Inventory of Criminal Thinking Styles (PICTS), as a measure of cognitive styles, was more resistant to such minimization. Psychopathic traits, especially high Factor 1 scores (i.e., affective/interpersonal), were associated with greater PIM. Important differences in the willingness and ability to use deception were found based on the (a) mode of administration (i.e., interview vs. self-report) and (b) level of psychopathy as measured by the Psychopathy Checklist - Revised (PCL-R). The important implications of this research are discussed for risk assessment procedures regarding likely areas of deception and its detection. The current research also informs the growing literature on the connection between psychopathic traits and deception. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of secondary organic aerosol from photo-oxidation of gasoline exhaust and specific sources of major components.

PubMed

Ma, Pengkun; Zhang, Peng; Shu, Jinian; Yang, Bo; Zhang, Haixu

2018-01-01

To further explore the composition and distribution of secondary organic aerosol (SOA) components from the photo-oxidation of light aromatic precursors (toluene, m-xylene, and 1,3,5-trimethylbenzene (1,3,5-TMB)) and idling gasoline exhaust, a vacuum ultraviolet photoionization mass spectrometer (VUV-PIMS) was employed. Peaks of the molecular ions of the SOA components with minimum molecular fragmentation were clearly observed from the mass spectra of SOA, through the application of soft ionization methods in VUV-PIMS. The experiments comparing the exhaust-SOA and light aromatic mixture-SOA showed that the observed distributions of almost all the predominant cluster ions in the exhaust-SOA were similar to that of the mixture-SOA. Based on the characterization experiments of SOA formed from individual light aromatic precursors, the SOA components with molecular weights of 98 and 110 amu observed in the exhaust-SOA resulted from the photo-oxidation of toluene and m-xylene; the components with a molecular weight of 124 amu were derived mainly from m-xylene; and the components with molecular weights of 100, 112, 128, 138, and 156 amu were mainly derived from 1,3,5-TMB. These results suggest that C 7 -C 9 light aromatic hydrocarbons are significant SOA precursors and that major SOA components originate from gasoline exhaust. Additionally, some new light aromatic hydrocarbon-SOA components were observed for the first time using VUV-PIMS. The corresponding reaction mechanisms were also proposed in this study to enrich the knowledge base of the formation mechanisms of light aromatic hydrocarbon-SOA compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Single crystal CVD diamond membranes for betavoltaic cells

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

Delfaure, C.; Pomorski, M., E-mail: michal.pomorski@cea.fr; Sanoit, J. de

2016-06-20

A single crystal diamond large area thin membrane was assembled as a p-doped/Intrinsic/Metal (PIM) structure and used in a betavoltaic configuration. When tested with a 20 keV electron beam from a high resolution scanning electron microscope, we measured an open circuit voltage (V{sub oc}) of 1.85 V, a charge collection efficiency (CCE) of 98%, a fill-factor of 80%, and a total conversion efficiency of 9.4%. These parameters are inherently linked to the diamond membrane PIM structure that allows full device depletion even at 0 V and are among the highest reported up to now for any other material tested for betavoltaic devices. Itmore » enables to drive a high short-circuit current I{sub sc} up to 7.12 μA, to reach a maximum power P{sub max} of 10.48 μW, a remarkable value demonstrating the high-benefit of diamond for the realization of long-life radioisotope based micro-batteries.« less

Computational search for aflatoxin binding proteins

NASA Astrophysics Data System (ADS)

Wang, Ying; Liu, Jinfeng; Zhang, Lujia; He, Xiao; Zhang, John Z. H.

2017-10-01

Aflatoxin is one of the mycotoxins that contaminate various food products. Among various aflatoxin types (B1, B2, G1, G2 and M1), aflatoxin B1 is the most important and the most toxic one. In this study, through computational screening, we found that several proteins may bind specifically with different type of aflatoxins. Combination of theoretical methods including target fishing, molecular docking, molecular dynamics (MD) simulation, MM/PBSA calculation were utilized to search for new aflatoxin B1 binding proteins. A recently developed method for calculating entropic contribution to binding free energy called interaction entropy (IE) was employed to compute the binding free energy between the protein and aflatoxin B1. Through comprehensive comparison, three proteins, namely, trihydroxynaphthalene reductase, GSK-3b, and Pim-1 were eventually selected as potent aflatoxin B1 binding proteins. GSK-3b and Pim-1 are drug targets of cancers or neurological diseases. GSK-3b is the strongest binder for aflatoxin B1.

Powder Injection Molding for mass production of He-cooled divertor parts

NASA Astrophysics Data System (ADS)

Antusch, S.; Norajitra, P.; Piotter, V.; Ritzhaupt-Kleissl, H.-J.

2011-10-01

A He-cooled divertor for future fusion power plants has been developed at KIT. Tungsten and tungsten alloys are presently considered the most promising materials for functional and structural divertor components. The advantages of tungsten materials lie, e.g. in the high melting point, and low activation, the disadvantages are high hardness and brittleness. The machinig of tungsten, e.g. milling, is very complex and cost-intensive. Powder Injection Molding (PIM) is a method for cost effective mass production of near-net-shape parts with high precision. The complete W-PIM process route is outlined and, results of product examination discussed. A binary tungsten powder feedstock with a grain size distribution in the range 0.7-1.7 μm FSSS, and a solid load of 50 vol.% was developed. After heat treatment, the successfully finished samples showed promising results, i.e. 97.6% theoretical density, a grain size of approximately 5 μm, and a hardness of 457 HV0.1.

David Florida Laboratory: Support for mobile satellite communications

NASA Technical Reports Server (NTRS)

Dumoulin, Jean-Guy; Mamen, Rolf

1995-01-01

The comprehensive integration and environmental (including RF) test facilities of the Canadian Space Agency's David Florida Laboratory (CSA)(DFL) were used extensively for the MSAT Program. Following a description of the facilities, the paper outlines their application to the qualification of the two MSAT satellites following an overview of the test plan. Particular emphasis is given to passive intermodulation measurement (PIM) demands, which for the MSAT satellites, contributed to the need to extend the anechoic chamber. The extended chamber was also used for an EMC test and SAR signature test of the RADARSAT satellite. The DFL's facilities are being used for additional aspects of mobile satellite communications. One shielded anechoic Extra High Frequency (EHF) chamber and associated test equipment are employed predominantly for measuring the performance of the IRIDIUM satellites' Engineering Model Gateway Moveable Antennas (EM)(GMA). Other chambers are used for testing aeronautical antennas on behalf of Inmarsat. Still others combine thermal and PIM testing. The paper concludes with a review of the test requirements of evolving satcom missions such as Inmarsat Aero-1.

Mastery Learning through Individualized Instruction: A Reinforcement Strategy

ERIC Educational Resources Information Center

Sagy, John; Ravi, R.; Ananthasayanam, R.

2009-01-01

The present study attempts to gauge the effect of individualized instructional methods as a reinforcement strategy for mastery learning. Among various individualized instructional methods, the study focuses on PIM (Programmed Instructional Method) and CAIM (Computer Assisted Instruction Method). Mastery learning is a process where students achieve…

Organizing Scientific Data Sets: Studying Similarities and Differences in Metadata and Subject Term Creation

ERIC Educational Resources Information Center

White, Hollie C.

2012-01-01

Background: According to Salo (2010), the metadata entered into repositories are "disorganized" and metadata schemes underlying repositories are "arcane". This creates a challenging repository environment in regards to personal information management (PIM) and knowledge organization systems (KOSs). This dissertation research is…

7 CFR 300.4 - Reference Manual B.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., 2001, by the National Seed Health System (NSHS), has been approved for incorporation by reference in 7... inspection at the APHIS Library, U.S. Department of Agriculture, 4700 River Road, Riverdale, MD or at the... the APHIS Web site at http://www.aphis.usda.gov/ppq/pim/accreditation. ...

Positioning In Macular hole Surgery (PIMS): statistical analysis plan for a randomised controlled trial.

PubMed

Bell, Lauren; Hooper, Richard; Bunce, Catey; Pasu, Saruban; Bainbridge, James

2017-06-13

The treatment of idiopathic full-thickness macular holes involves surgery to close the hole. Some surgeons advise patients to adopt a face-down position to increase the likelihood of successful macular hole closure. However, patients often find the face-down positioning arduous. There is a lack of conclusive evidence that face-down positioning improves the outcome. The 'Positioning In Macular hole Surgery' (PIMS) trial will assess whether advice to position face-down after surgery improves the surgical success rate for the closure of large (≥400 μm) macular holes. The PIMS trial is a multicentre, parallel-group, superiority clinical trial with 1:1 randomisation. Patients (n = 192) with macular holes (≥400 μm) will be randomised after surgery to either face-down positioning or face-forward positioning for at least 8 h (which can be either consecutive or nonconsecutive) a day, for 5 days following surgery. Inclusion criteria are: presence of an idiopathic full-thickness macular hole ≥400 μm in diameter, as measured by optical coherence tomography (OCT) scans, on either or both eyes; patients electing to have surgery for a macular hole, with or without simultaneous phacoemulsification and intraocular lens implant; ability and willingness to position face-down or in an inactive face-forward position; a history of visual loss suggesting a macular hole of 12 months' or less duration. The primary outcome is successful macular hole closure at 3 months post surgery. The treatment effect will be reported as an odds ratio with 95% confidence interval, adjusted for size of macular hole and phakic lens status at baseline. Secondary outcome measures at 3 months are: further surgery for macular holes performed or planned (of those with unsuccessful closure); patient-reported experience of positioning; whether patients report they would still have elected to have the operation given what they know at follow-up; best-corrected visual acuity (BCVA) measured using Snellen charts at a standard distance of 6 m; patient-reported health and quality of life assessed using the National Eye Institute Visual Function Questionnaire (VFQ-25). The PIMS trial is the first multicentre randomised control trial to investigate the value of face-down positioning following macular hole standardised surgery. International Standard Randomised Controlled Trials Number registry, ID: ISRCTN12410596. Registered on 11 February 2015. United Kingdom Clinical Research Network, ID: UKCRN17966 . Registered on 26 November 2014.

Alignment, orientation, and Coulomb explosion of difluoroiodobenzene studied with the pixel imaging mass spectrometry (PImMS) camera.

PubMed

Amini, Kasra; Boll, Rebecca; Lauer, Alexandra; Burt, Michael; Lee, Jason W L; Christensen, Lauge; Brauβe, Felix; Mullins, Terence; Savelyev, Evgeny; Ablikim, Utuq; Berrah, Nora; Bomme, Cédric; Düsterer, Stefan; Erk, Benjamin; Höppner, Hauke; Johnsson, Per; Kierspel, Thomas; Krecinic, Faruk; Küpper, Jochen; Müller, Maria; Müller, Erland; Redlin, Harald; Rouzée, Arnaud; Schirmel, Nora; Thøgersen, Jan; Techert, Simone; Toleikis, Sven; Treusch, Rolf; Trippel, Sebastian; Ulmer, Anatoli; Wiese, Joss; Vallance, Claire; Rudenko, Artem; Stapelfeldt, Henrik; Brouard, Mark; Rolles, Daniel

2017-07-07

Laser-induced adiabatic alignment and mixed-field orientation of 2,6-difluoroiodobenzene (C 6 H 3 F 2 I) molecules are probed by Coulomb explosion imaging following either near-infrared strong-field ionization or extreme-ultraviolet multi-photon inner-shell ionization using free-electron laser pulses. The resulting photoelectrons and fragment ions are captured by a double-sided velocity map imaging spectrometer and projected onto two position-sensitive detectors. The ion side of the spectrometer is equipped with a pixel imaging mass spectrometry camera, a time-stamping pixelated detector that can record the hit positions and arrival times of up to four ions per pixel per acquisition cycle. Thus, the time-of-flight trace and ion momentum distributions for all fragments can be recorded simultaneously. We show that we can obtain a high degree of one-and three-dimensional alignment and mixed-field orientation and compare the Coulomb explosion process induced at both wavelengths.

Advancing polymers of intrinsic microporosity by mechanochemistry

DOE PAGES

Zhang, Pengfei; Jiang, Xueguang; Wan, Shun; ...

2015-02-20

Herein, we report a fast (15 min) and solvent-free mechanochemical approach to construct polymers of intrinsic microporosity (PIMs) with high molecular mass and low polydispersity by solid grinding. The enhanced reaction efficiency results from the instantaneous frictional heating and continuous exposure of active sites within those solid reactants.

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

Bakoglidis, Konstantinos D., E-mail: konba@ifm.liu.se; Schmidt, Susann; Garbrecht, Magnus

The potential of different magnetron sputtering techniques for the synthesis of low friction and wear resistant amorphous carbon nitride (a-CN{sub x}) thin films onto temperature-sensitive AISI52100 bearing steel, but also Si(001) substrates was studied. Hence, a substrate temperature of 150 °C was chosen for the film synthesis. The a-CN{sub x} films were deposited using mid-frequency magnetron sputtering (MFMS) with an MF bias voltage, high power impulse magnetron sputtering (HiPIMS) with a synchronized HiPIMS bias voltage, and direct current magnetron sputtering (DCMS) with a DC bias voltage. The films were deposited using a N{sub 2}/Ar flow ratio of 0.16 at the totalmore » pressure of 400 mPa. The negative bias voltage, V{sub s}, was varied from 20 to 120 V in each of the three deposition modes. The microstructure of the films was characterized by high-resolution transmission electron microscopy and selected area electron diffraction, while the film morphology was investigated by scanning electron microscopy. All films possessed an amorphous microstructure, while the film morphology changed with the bias voltage. Layers grown applying the lowest substrate bias of 20 V exhibited pronounced intercolumnar porosity, independent of the sputter technique. Voids closed and dense films are formed at V{sub s} ≥ 60 V, V{sub s} ≥ 100 V, and V{sub s} = 120 V for MFMS, DCMS, and HiPIMS, respectively. X-ray photoelectron spectroscopy revealed that the nitrogen-to-carbon ratio, N/C, of the films ranged between 0.2 and 0.24. Elastic recoil detection analysis showed that Ar content varied between 0 and 0.8 at. % and increased as a function of V{sub s} for all deposition techniques. All films exhibited compressive residual stress, σ, which depends on the growth method; HiPIMS produces the least stressed films with values ranging between −0.4 and −1.2 GPa for all V{sub s}, while CN{sub x} films deposited by MFMS showed residual stresses up to −4.2 GPa. Nanoindentation showed a significant increase in film hardness and reduced elastic modulus with increasing V{sub s} for all techniques. The harder films were produced by MFMS with hardness as high as 25 GPa. Low friction coefficients, between 0.05 and 0.06, were recorded for all films. Furthermore, CN{sub x} films produced by MFMS and DCMS at V{sub s} = 100 and 120 V presented a high wear resistance with wear coefficients of k ≤ 2.3 × 10{sup −5} mm{sup 3}/Nm. While all CN{sub x} films exhibit low friction, wear depends strongly on the structural and mechanical characteristics of the films. The MFMS mode is best suited for the production of hard CN{sub x} films, although high compressive stresses challenge the application on steel substrates. Films grown in HiPIMS mode provide adequate adhesion due to low residual stress values, at the expense of lower film hardness. Thus, a relatively wide mechanical property envelope is presented for CN{sub x} films, which is relevant for the optimization of CN{sub x} film properties intended to be applied as low friction and wear resistant coatings.« less

Acceleration Environment of the International Space Station

NASA Technical Reports Server (NTRS)

McPherson, Kevin; Kelly, Eric; Keller, Jennifer

2009-01-01

Measurement of the microgravity acceleration environment on the International Space Station has been accomplished by two accelerometer systems since 2001. The Microgravity Acceleration Measurement System records the quasi-steady microgravity environment, including the influences of aerodynamic drag, vehicle rotation, and venting effects. Measurement of the vibratory/transient regime, comprised of vehicle, crew, and equipment disturbances, has been accomplished by the Space Acceleration Measurement System-II. Until the arrival of the Columbus Orbital Facility and the Japanese Experiment Module, the location of these sensors, and therefore, the measurement of the microgravity acceleration environment, has been limited to within the United States Laboratory. Japanese Aerospace Exploration Agency has developed a vibratory acceleration measurement system called the Microgravity Measurement Apparatus which will be deployed within the Japanese Experiment Module to make distributed measurements of the Japanese Experiment Module's vibratory acceleration environment. Two Space Acceleration Measurement System sensors from the United States Laboratory will be re-deployed to support vibratory acceleration data measurement within the Columbus Orbital Facility. The additional measurement opportunities resulting from the arrival of these new laboratories allows Principal Investigators with facilities located in these International Space Station research laboratories to obtain microgravity acceleration data in support of their sensitive experiments. The Principal Investigator Microgravity Services project, at NASA Glenn Research Center, in Cleveland, Ohio, has supported acceleration measurement systems and the microgravity scientific community through the processing, characterization, distribution, and archival of the microgravity acceleration data obtained from the International Space Station acceleration measurement systems. This paper summarizes the PIMS capabilities available to the International Space Station scientific community, introduces plans for extending microgravity analysis results to the newly arrived scientific laboratories, and provides summary information for known microgravity environment disturbers.

Hardware Acceleration of Sparse Cognitive Algorithms

DTIC Science & Technology

2016-05-01

Processor in Memory (PiM) extensions and a 65 nm ASIC version. They were compared against a 28 nm GPU baseline using the KTH video action recognition...30 Table 17. Memory Requirement of Proposed ASIC...for improvement of performance per unit of power for customized implementations of the Sparsey and Numenta Hierarchical Temporal Memory (HTM

Overcoming Resistance to Inhibitors of the Akt Protein Kinase by Modulation of the Pim Kinase Pathway

DTIC Science & Technology

2014-10-01

during hypoxia were biologically meaningful, we investigated the activity of a reporter with multiple HIF binding sites ( HRE ) in front of a luciferase...inhibitors in a dose dependent fashion blocked the activity of the HRE to activate luciferase mRNA and protein production. This result demonstrates that

A Personal Intelligent Mentor for Promoting Metacognition in Solving Logic Word Puzzles.

ERIC Educational Resources Information Center

Baylor, Amy L.; Kozbe, Barcin

This paper describes a Personal Intelligent Mentor (PIM) that facilitates metacognitive development in the domain of solving logic word puzzles. Metacognition is an important aspect for critical thinking skills. High school students must develop logical and critical thinking abilities as a prerequisite for higher-level math and computer…

75 FR 77931 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... Exchange, Inc. (``CBOE'') currently charges a marketing fee of up to $0.65 per contract for customer orders... a Public Customer Order in the Exchange's Price Improvement Mechanism (``PIM''). For competitive reasons, the Exchange now proposes to apply its PFOF fee for Public Customer Orders executed in the...

Enhancing Cognitive Presence in Online Case Discussions with Questions Based on the Practical Inquiry Model

ERIC Educational Resources Information Center

Sadaf, Ayesha; Olesova, Larisa

2017-01-01

The researchers in this study examined the influence of questions designed with the Practical Inquiry Model (PIM), compared with the regular (playground) questions, on students' levels of cognitive presence in online discussions. Students' discussion postings were collected and categorized according to the four levels of cognitive presence:…

The Impact Analysis of a Mixed Squadron, Containing LCS and Multi-Mission Surface Platforms, on Blue Force Casualties and Mission Effectiveness

DTIC Science & Technology

2008-09-01

Littoral Combat Ships OTH Over-The-Horizon Pd Probability of Detection PGGF Fast Attack Craft – Missile PIM Plan of Intended Movement Pk...Lucas Naval Postgraduate School Monterey, California 2. Dudley Knox Library Naval Postgraduate School Monterey, California 3. CAPT Doug Otte

Organic and inorganic matter in Louisiana coastal waters: Vermilion, Atchafalaya, Terrebonne, Barataria, and Mississippi regions.

PubMed

Schaeffer, Blake A; Conmy, Robyn N; Aukamp, Jessica; Craven, George; Ferer, Erin J

2011-02-01

Chromophoric dissolved organic matter (CDOM) spectral absorption, dissolved organic carbon (DOC) concentration, and the particulate fraction of inorganic (PIM) and organic matter (POM) were measured in Louisiana coastal waters at Vermilion, Atchafalaya, Terrebonne, Barataria, and Mississippi River locations, in 2007-2008. The range of CDOM was 0.092 m⁻¹ at Barataria in June 2008 to 11.225 m⁻¹ at Mississippi in February 2008. An indicator of organic matter quality was predicted by the spectral slope of absorption coefficients from 350 to 412nm which was between 0.0087 m⁻¹ at Mississippi in May 2008 and 0.0261 m⁻¹ at Barataria in June 2008. CDOM was the dominant component of light attenuation at Terrebonne and Barataria. Detritus and CDOM were the primary components of light attenuation at Vermilion, Atchafalaya, and Mississippi. DOC ranged between 65 and 1235 μM. PIM ranged between 1.1 and 426.3 mg L⁻¹ and POM was between 0.3 and 49.6 mg L⁻¹. Published by Elsevier Ltd.

Phase time delay and Hartman effect in a one-dimensional photonic crystal with four-level atomic defect layer

NASA Astrophysics Data System (ADS)

Jamil, Rabia; Ali, Abu Bakar; Abbas, Muqaddar; Badshah, Fazal; Qamar, Sajid

2017-08-01

The Hartman effect is revisited using a Gaussian beam incident on a one-dimensional photonic crystal (1DPC) having a defect layer doped with four-level atoms. It is considered that each atom of the defect layer interacts with three driving fields, whereas a Gaussian beam of width w is used as a probe light to study Hartman effect. The atom-field interaction inside the defect layer exhibits electromagnetically induced transparency (EIT). The 1DPC acts as positive index material (PIM) and negative index material (NIM) corresponding to the normal and anomalous dispersion of the defect layer, respectively, via control of the phase associated with the driving fields and probe detuning. The positive and negative Hartman effects are noticed for PIM and NIM, respectively, via control of the relative phase corresponding to the driving fields and probe detuning. The advantage of using four-level EIT system is that a much smaller absorption of the transmitted beam occurs as compared to three-level EIT system corresponding to the anomalous dispersion, leading to negative Hartman effect.

In Silico Determination of Gas Permeabilities by Non-Equilibrium Molecular Dynamics: CO2 and He through PIM-1

PubMed Central

Frentrup, Hendrik; Hart, Kyle E.; Colina, Coray M.; Müller, Erich A.

2015-01-01

We study the permeation dynamics of helium and carbon dioxide through an atomistically detailed model of a polymer of intrinsic microporosity, PIM-1, via non-equilibrium molecular dynamics (NEMD) simulations. This work presents the first explicit molecular modeling of gas permeation through a high free-volume polymer sample, and it demonstrates how permeability and solubility can be obtained coherently from a single simulation. Solubilities in particular can be obtained to a very high degree of confidence and within experimental inaccuracies. Furthermore, the simulations make it possible to obtain very specific information on the diffusion dynamics of penetrant molecules and yield detailed maps of gas occupancy, which are akin to a digital tomographic scan of the polymer network. In addition to determining permeability and solubility directly from NEMD simulations, the results shed light on the permeation mechanism of the penetrant gases, suggesting that the relative openness of the microporous topology promotes the anomalous diffusion of penetrant gases, which entails a deviation from the pore hopping mechanism usually observed in gas diffusion in polymers. PMID:25764366

Real-time monitoring of trace-level VOCs by an ultrasensitive lamp-based VUV photoionization mass spectrometer

NASA Astrophysics Data System (ADS)

Sun, W. Q.; Shu, J. N.; Zhang, P.; Li, Z.; Li, N. N.; Liang, M.; Yang, B.

2015-11-01

In this study, we report on the development of a lamp-based vacuum ultraviolet photoionization mass spectrometer (VUV-PIMS) in our laboratory; it is composed of a radio-frequency-powered VUV lamp, a VUV photoionizer, an ion-migration lens assembly, and a reflection time-of-flight mass spectrometer. By utilizing the novel photoionizer consisting of a photoionization cavity and a VUV light baffle, the baselines of the mass spectra decreased from 263.6 ± 15.7 counts to 4.1 ± 1.8 counts. A detection limit (2σ) of 3 pptv was achieved for benzene after an acquisition time of 10 s. To examine its potential for real-time monitoring applications of samples, the developed VUV-PIMS was employed for the continuous measurement of urban air for 6 days in Beijing, China. Strong signals of trace-level volatile organic compounds, such as benzene and its alkylated derivatives, were observed in the mass spectra. These initial experimental results reveal that the instrument can be used for the online monitoring of trace-level species in the atmosphere.

More evidence for azimuthal ion spin in HiPIMS discharges

NASA Astrophysics Data System (ADS)

Poolcharuansin, P.; Liebig, B.; Bradley, J. W.

2012-02-01

The velocity and energy distribution functions of ions escaping radially from the magnetic trap region of a HiPIMS discharge have been measured using a retarding field analyzer (RFA). Spatially and angularly resolved measurements recorded at a representative time show more energetic ions detected along a line-of-sight coincident with an oncoming rotating ion fluid, which circulates above the racetrack in the same direction as the electron E × B drift. The difference in the mean ion energies between measurements made into and against the direction of rotation is ~5 eV. Numerical solutions of the equation of motion for the ions accounting for azimuthal acceleration (modified two-stream instability model used by Lundin et al) have been found. The centripetal force caused by the radial electric field and a drag force term accounting for ion collisions revealed that only a small fraction (typically <5%) of the circulating ion flux can leave the discharge tangentially. Operating the discharge at different background pressures revealed an interplay between the azimuthal acceleration of ions, dominating under low pressure conditions and the scattering of ions into the RFA at higher pressure.

Polypharmacy, drug-drug interactions, and potentially inappropriate medications in older adults with human immunodeficiency virus infection.

PubMed

Greene, Meredith; Steinman, Michael A; McNicholl, Ian R; Valcour, Victor

2014-03-01

To describe the frequency of medication-related problems in older adults with human immunodeficiency virus (HIV) infection. Retrospective chart review. Community. HIV-positive individuals aged 60 and older and age- and sex-matched HIV-negative individuals. Total number of medications, potentially inappropriate medications (PIMs) according to the modified Beers Criteria, anticholinergic drug burden according to the Anticholinergic Risk Scale (ARS), and drug-drug interactions using the Lexi-Interact online drug interactions database. Of 89 HIV-positive participants, most were Caucasian (91%) and male (94%), with a median age of 64 (range 60-82). Common comorbidities included hyperlipidemia, hypertension, and depression. Participants were taking a median of 13 medications (range 2-38), of which only a median of four were antiretrovirals. At least one PIM was prescribed in 46 participants (52%). Sixty-two (70%) participants had at least one Category D (consider therapy modification) drug-drug interaction, and 10 (11%) had a Category X (avoid combination) interaction. One-third of these interactions were between two nonantiretroviral medications. Fifteen participants (17%) had an ARS score of 3 or greater. In contrast, HIV-negative participants were taking a median of six medications, 29% had at least one PIM, and 4% had an ARS score of 3 or greater (P < .05 for each comparison, except P = .07 for anticholinergic burden). HIV-positive older adults have a high frequency of medication-related problems, of which a large portion is due to medications used to treat comorbid diseases. These medication issues were substantially higher than HIV-negative participants. Attention to the principles of geriatric prescribing is needed as this population ages in order to minimize complications from multiple medication use. © Published 2014. This article is a U.S. Government work and is in the public domain in the U.S.A.

An estimate of the cost of administering intravenous biological agents in Spanish day hospitals

PubMed Central

Nolla, Joan Miquel; Martín, Esperanza; Llamas, Pilar; Manero, Javier; Rodríguez de la Serna, Arturo; Fernández-Miera, Manuel Francisco; Rodríguez, Mercedes; López, José Manuel; Ivanova, Alexandra; Aragón, Belén

2017-01-01

Objective To estimate the unit costs of administering intravenous (IV) biological agents in day hospitals (DHs) in the Spanish National Health System. Patients and methods Data were obtained from 188 patients with rheumatoid arthritis, collected from nine DHs, receiving one of the following IV therapies: infliximab (n=48), rituximab (n=38), abatacept (n=41), or tocilizumab (n=61). The fieldwork was carried out between March 2013 and March 2014. The following three groups of costs were considered: 1) structural costs, 2) material costs, and 3) staff costs. Staff costs were considered a fixed cost and were estimated according to the DH theoretical level of activity, which includes, as well as personal care of each patient, the DH general activities (complete imputation method, CIM). In addition, an alternative calculation was performed, in which the staff costs were considered a variable cost imputed according to the time spent on direct care (partial imputation method, PIM). All costs were expressed in euros for the reference year 2014. Results The average total cost was €146.12 per infusion (standard deviation [SD] ±87.11; CIM) and €29.70 per infusion (SD ±11.42; PIM). The structure-related costs per infusion varied between €2.23 and €62.35 per patient and DH; the cost of consumables oscillated between €3.48 and €20.34 per patient and DH. In terms of the care process, the average difference between the shortest and the longest time taken by different hospitals to administer an IV biological therapy was 113 minutes. Conclusion The average total cost of infusion was less than that normally used in models of economic evaluation coming from secondary sources. This cost is even less when the staff costs are imputed according to the PIM. A high degree of variability was observed between different DHs in the cost of the consumables, in the structure-related costs, and in those of the care process. PMID:28356746

Undisclosed conflicts of interest among biomedical textbook authors.

PubMed

Piper, Brian J; Lambert, Drew A; Keefe, Ryan C; Smukler, Phoebe U; Selemon, Nicolas A; Duperry, Zachary R

2018-02-05

Textbooks are a formative resource for health care providers during their education and are also an enduring reference for pathophysiology and treatment. Unlike the primary literature and clinical guidelines, biomedical textbook authors do not typically disclose potential financial conflicts of interest (pCoIs). The objective of this study was to evaluate whether the authors of textbooks used in the training of physicians, pharmacists, and dentists had appreciable undisclosed pCoIs in the form of patents or compensation received from pharmaceutical or biotechnology companies. The most recent editions of six medical textbooks, Harrison's Principles of Internal Medicine ( Har PIM), Katzung and Trevor's Basic and Clinical Pharmacology ( Kat BCP), the American Osteopathic Association's Foundations of Osteopathic Medicine ( AOA FOM), Remington: The Science and Practice of Pharmacy ( Rem SPP), Koda-Kimble and Young's Applied Therapeutics ( KKY AT), and Yagiela's Pharmacology and Therapeutics for Dentistry ( Yag PTD), were selected after consulting biomedical educators for evaluation. Author names (N = 1,152, 29.2% female) were submitted to databases to examine patents (Google Scholar) and compensation (ProPublica's Dollars for Docs [PDD]). Authors were listed as inventors on 677 patents (maximum/author = 23), with three-quarters (74.9%) to Har PIM authors. Females were significantly underrepresented among patent holders. The PDD 2009-2013 database revealed receipt of US$13.2 million, the majority to (83.9%) to Har PIM. The maximum compensation per author was $869,413. The PDD 2014 database identified receipt of $6.8 million, with 50.4% of eligible authors receiving compensation. The maximum compensation received by a single author was $560,021. Cardiovascular authors were most likely to have a PDD entry and neurologic disorders authors were least likely. An appreciable subset of biomedical authors have patents and have received remuneration from medical product companies and this information is not disclosed to readers. These findings indicate that full transparency of financial pCoI should become a standard practice among the authors of biomedical educational materials.

Reactive sputtering of δ-ZrH{sub 2} thin films by high power impulse magnetron sputtering and direct current magnetron sputtering

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

Högberg, Hans, E-mail: hans.hogberg@liu.se; Tengdelius, Lina; Eriksson, Fredrik

2014-07-01

Reactive sputtering by high power impulse magnetron sputtering (HiPIMS) and direct current magnetron sputtering (DCMS) of a Zr target in Ar/H{sub 2} plasmas was employed to deposit Zr-H films on Si(100) substrates, and with H content up to 61 at. % and O contents typically below 0.2 at. % as determined by elastic recoil detection analysis. X-ray photoelectron spectroscopy reveals a chemical shift of ∼0.7 eV to higher binding energies for the Zr-H films compared to pure Zr films, consistent with a charge transfer from Zr to H in a zirconium hydride. X-ray diffraction shows that the films are single-phase δ-ZrH{sub 2} (CaF{submore » 2} type structure) at H content >∼55 at. % and pole figure measurements give a 111 preferred orientation for these films. Scanning electron microscopy cross-section images show a glasslike microstructure for the HiPIMS films, while the DCMS films are columnar. Nanoindentation yield hardness values of 5.5–7 GPa for the δ-ZrH{sub 2} films that is slightly harder than the ∼5 GPa determined for Zr films and with coefficients of friction in the range of 0.12–0.18 to compare with the range of 0.4–0.6 obtained for Zr films. Wear resistance testing show that phase-pure δ-ZrH{sub 2} films deposited by HiPIMS exhibit up to 50 times lower wear rate compared to those containing a secondary Zr phase. Four-point probe measurements give resistivity values in the range of ∼100–120 μΩ cm for the δ-ZrH{sub 2} films, which is slightly higher compared to Zr films with values in the range 70–80 μΩ cm.« less

The use of segmented cathodes to determine the spoke current density distribution in high power impulse magnetron sputtering plasmas

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

Poolcharuansin, Phitsanu; The Technological Plasma Research Unit, Department of Physics, Mahasarakham University, Maha Sarakham 44150; Estrin, Francis Lockwood

2015-04-28

The localized target current density associated with quasi-periodic ionization zones (spokes) has been measured in a high power impulse magnetron sputtering (HiPIMS) discharge using an array of azimuthally separated and electrical isolated probes incorporated into a circular aluminum target. For a particular range of operating conditions (pulse energies up to 2.2 J and argon pressures from 0.2 to 1.9 Pa), strong oscillations in the probe current density are seen with amplitudes up to 52% above a base value. These perturbations, identified as spokes, travel around the discharge above the target in the E×B direction. Using phase information from the angularly separated probes,more » the spoke drift speeds, angular frequencies, and mode number have been determined. Generally, at low HiPIMS pulse energies E{sub p} < 0.8 J, spokes appear to be chaotic in nature (with random arrival times), however as E{sub p} increases, coherent spokes are observed with velocities between 6.5 and 10 km s{sup −1} and mode numbers m = 3 or above. At E{sub p} > 1.8 J, the plasma becomes spoke-free. The boundaries between chaotic, coherent, and no-spoke regions are weakly dependent on pressure. During each HiPIMS pulse, the spoke velocities increase by about 50%. Such an observation is explained by considering spoke velocities to be determined by the critical ionization velocity, which changes as the plasma composition changes during the pulse. From the shape of individual current density oscillations, it appears that the leading edge of the spoke is associated with a slow increase in local current density to the target and the rear with a more rapid decrease. The measurements show that the discharge current density associated with individual spokes is broadly spread over a wide region of the target.« less

Effects of short-term tocopherol (T) feeding on structure-localized protein tyrosine nitration (pTN) patterns of mitochondrial ATPase following endotoxin (LPS) challenge in beef calves.

USDA-ARS?s Scientific Manuscript database

Mitochondrial ATPase/Complex-V (MCV) is an electron transport chain (ETC) component needed for ATP synthesis. The ETC, exquisitely sensitive to proinflammatory mediators (PIM), generates oxynitrogen reactants leading to pTN formation as mitochondrial membrane leakage occurs. Immunohistochemical loca...

Nature of Cirrus

DTIC Science & Technology

1992-12-23

shown in figures 12 and 13. In figure 12 a 60 Pm image of the Andromeda nebula M 31 as generated using HIRAS is shown. The resolution in this image...Cambridge, UK 17 Figure 12: The Andromeda Nebula (M31) at 60 pim as processed by HIRAS. The size of the tmage is 2.80 . The resolution is about 1’ (factor 5

Optical Pumping of Molecular Gases

DTIC Science & Technology

1976-04-01

ser emission ott a The typical experimental apparatus is shown i.- Fig. *series of green and yellow molecular B-X’-basnd transi- 2. For B-bantd optical...with A, at 0. 473 pim and that Na2 may operate as a flash -lamp -pumped laser X,... at 0. 54 umn the Doppler widths are AwD - 12.42 source with buffer

U.S. EPA, Pesticide Product Label, TDC DICOFOL 4E, 02/19/1982

EPA Pesticide Factsheets

2011-04-21

... kJI ~ ...-I ~ ... M<1 ~ IIrf'Ie(II.-cI -- roc D«X>fOt '·E CWI be ~ 8IIOnI or 'tII"Ith ott>.f ~~ ... t9COiI ••• ded 'Pf'-r ~ • ttIouId Ml ~ ....s wtth limit or ... y ~ tIO .-piM.! ...

Diatomaceous Fungal and Bacterial Building Blocks for Material Synthesis

DTIC Science & Technology

2008-04-08

Thalassiosira-templated metallic microshells. Thalassiosira, only 1mM rhodamine 6G (d) lmM, (e) I piM ,(f 100 nM R6G. 4 concentrations gave detectable...hybridized with a 27-mer 7 oligonucleotide containing a 7-mer TAG GAA TAG TTA TA AT OTT ATT AGO complementary region 2, which produces TAIOATCCTTA TACAATAATCC

Investigation of ionized metal flux in enhanced high power impulse magnetron sputtering discharges

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

Stranak, Vitezslav, E-mail: stranak@prf.jcu.cz; Hubicka, Zdenek; Cada, Martin

2014-04-21

The metal ionized flux fraction and production of double charged metal ions Me{sup 2+} of different materials (Al, Cu, Fe, Ti) by High Power Impulse Magnetron Sputtering (HiPIMS) operated with and without a pre-ionization assistance is compared in the paper. The Electron Cyclotron Wave Resonance (ECWR) discharge was employed as the pre-ionization agent providing a seed of charge in the idle time of HiPIMS pulses. A modified grid-free biased quartz crystal microbalance was used to estimate the metal ionized flux fraction ξ. The energy-resolved mass spectrometry served as a complementary method to distinguish particular ion contributions to the total ionizedmore » flux onto the substrate. The ratio between densities of doubly Me{sup 2+} and singly Me{sup +} charged metal ions was determined. It is shown that ECWR assistance enhances Me{sup 2+} production with respect of absorbed rf-power. The ECWR discharge also increases the metal ionized flux fraction of about 30% especially in the region of lower pressures. Further, the suppression of the gas rarefaction effect due to enhanced secondary electron emission of Me{sup 2+} was observed.« less

Enhanced electrochemical capacitance of polyimidazole coated covellite CuS dispersed CNT composite materials for application in supercapacitors.

PubMed

Ravi, Seenu; Gopi, Chandu V V M; Kim, Hee Je

2016-08-02

Great attention has been paid to the design and synthesis of distinct core/shell heterostructures for high-performance supercapacitors. We have prepared unique heterostructures consisting of polyimidazole-coated copper sulphide over a carbon nanotube network (CuS@CNT) on nickel foam, which was accomplished through a facile and cost-effective solvothermal method combined with a dip coating process. Hexagonal covellite CuS nanoparticles were dispersed on CNTs using a solvothermal method where dimethylformamide and distilled water were used as solvents. The synthesized CuS and CuS@CNT supercapacitor electrode materials were thoroughly characterized. The polymer supported electrode (PIM/CuS@CNT) shows a high areal capacitance of 1.51 F cm(-2) at a current density of 1.2 A g(-1), which is higher than the CuS@CNT electrode and many other previously reported CuS electrode materials. After 1000 cycles at a high current density of 1.2 A g(-1), the retention rate is 92%, indicating good long-term cycling stability. These results indicate that the PIM/CuS@CNT electrode is promising for high-performance supercapacitor applications.

Manufacturing and characterization of PIM-W materials as plasma facing materials

NASA Astrophysics Data System (ADS)

Pintsuk, G.; Antusch, S.; Rieth, M.; Wirtz, M.

2016-02-01

Powder injection molding (PIM) was used to produce pure and particle reinforced W materials to be qualified for the use as plasma facing material. As alloying elements La2O3, Y2O3, TiC, and TaC were chosen with a particle size between 50 nm and 2.5 μm, depending on the alloying element. The fabrication of alloyed materials was done for different compositions using powder mixtures. Final sintering was performed in H2 atmosphere at 2400 °C resulting in plates of 55 × 22 × 4 mm3 with ˜98% theoretical density. The qualification of the materials was done via high heat flux testing in the electron beam facility JUDITH-1. Thereby, ELM-like 1000 thermal shock loads of 0.38 GW m-2 for 1 ms and 100 disruption like loads of 1.13 GW m-2 for 1 ms at a base temperature of 1000 °C were applied. The obtained damage characteristics, i.e. surface roughening and crack formation, were qualified versus an industrially manufactured pure reference tungsten material and linked to the material’s microstructure and mechanical properties.

A head-mounted display-based personal integrated-image monitoring system for transurethral resection of the prostate.

PubMed

Yoshida, Soichiro; Kihara, Kazunori; Takeshita, Hideki; Fujii, Yasuhisa

2014-12-01

The head-mounted display (HMD) is a new image monitoring system. We developed the Personal Integrated-image Monitoring System (PIM System) using the HMD (HMZ-T2, Sony Corporation, Tokyo, Japan) in combination with video splitters and multiplexers as a surgical guide system for transurethral resection of the prostate (TURP). The imaging information obtained from the cystoscope, the transurethral ultrasonography (TRUS), the video camera attached to the HMD, and the patient's vital signs monitor were split and integrated by the PIM System and a composite image was displayed by the HMD using a four-split screen technique. Wearing the HMD, the lead surgeon and the assistant could simultaneously and continuously monitor the same information displayed by the HMD in an ergonomically efficient posture. Each participant could independently rearrange the images comprising the composite image depending on the engaging step. Two benign prostatic hyperplasia (BPH) patients underwent TURP performed by surgeons guided with this system. In both cases, the TURP procedure was successfully performed, and their postoperative clinical courses had no remarkable unfavorable events. During the procedure, none of the participants experienced any HMD-wear related adverse effects or reported any discomfort.

Protective effect of rutin on cognitive impairment caused by phenytoin

PubMed Central

Dubey, Shagun; Ganeshpurkar, Aditya; Bansal, Divya; Dubey, Nazneen

2015-01-01

Objective: To study the effect of the co-administration of phenytoin (PHT) and rutin in comparison with PHT and piracetam (PIM) on seizure control, cognitive, and motor functions in mice. Materials and Methods: Increasing current electroshock seizure (ICES) test was used to evaluate the effect of the co-administration of PHT and PIM on convulsions. Cognitive functions in mice were assessed by a spontaneous alternation in behavior on a plus maze while motor functions were screened using rolling roller apparatus and by counting the number of arms entries on a plus maze. Brain acetyl-cholinesterase (AChE) activity was also estimated. Statistical Analysis: The expression of data was done as mean ± standard error of the mean. The normally distributed data were subjected to one-way ANOVA followed by Dunnett's test. P < 0.05 was considered significant. Results: The study showed that rutin when co-administered with PHT, significantly reversed PHT-induced reduction in spontaneous alternation without altering the efficacy of PHT against ICES, in both acute and chronic studies. Further, it also reversed PHT-induced increase in AChE activity. Conclusion: Rutin alleviated the PHT-induced cognitive impairment without compromising its antiepileptic efficacy. PMID:26729954

Mixed-mode high-power impulse magnetron sputter deposition of tetrahedral amorphous carbon with pulse-length control of ionization

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

Tucker, M. D.; Marks, N. A.; Ganesan, R.

2016-04-21

High-power impulse magnetron sputtering (HiPIMS) is used to deposit amorphous carbon thin films with sp{sup 3} fractions of 13% to 82%. Increasing the pulse length results in a transition from conventional HiPIMS deposition to a “mixed-mode” in which an arc triggers on the target surface, resulting in a large flux of carbon ions. The films are characterized using X-ray photoelectron spectroscopy, Raman spectroscopy, ellipsometry, nanoindentation, elastic recoil detection analysis, and measurements of stress and contact angle. All properties vary in a consistent manner, showing a high tetrahedral character only for long pulses, demonstrating that mixed-mode deposition is the source ofmore » the high carbon ion flux. Varying the substrate bias reveals an “energy window” effect, where the sp{sup 3} fraction of the films is greatest for a substrate bias around −100 V and decreases for higher or lower bias values. In the absence of bias, the films' properties show little dependence on the pulse length, showing that energetic ions are the origin of the highly tetrahedral character.« less

Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease

PubMed Central

Bender, Tom; Lewrenz, Ilka; Franken, Sebastian; Baitzel, Catherina; Voos, Wolfgang

2011-01-01

Proteins in a natural environment are constantly challenged by stress conditions, causing their destabilization, unfolding, and, ultimately, aggregation. Protein aggregation has been associated with a wide variety of pathological conditions, especially neurodegenerative disorders, stressing the importance of adequate cellular protein quality control measures to counteract aggregate formation. To secure protein homeostasis, mitochondria contain an elaborate protein quality control system, consisting of chaperones and ATP-dependent proteases. To determine the effects of protein aggregation on the functional integrity of mitochondria, we set out to identify aggregation-prone endogenous mitochondrial proteins. We could show that major metabolic pathways in mitochondria were affected by the aggregation of key enzyme components, which were largely inactivated after heat stress. Furthermore, treatment with elevated levels of reactive oxygen species strongly influenced the aggregation behavior, in particular in combination with elevated temperatures. Using specific chaperone mutant strains, we showed a protective effect of the mitochondrial Hsp70 and Hsp60 chaperone systems. Moreover, accumulation of aggregated polypeptides was strongly decreased by the AAA-protease Pim1/LON. We therefore propose that the proteolytic breakdown of aggregation-prone polypeptides represents a major protective strategy to prevent the in vivo formation of aggregates in mitochondria. PMID:21209324

Towards higher stability of resonant absorption measurements in pulsed plasmas.

PubMed

Britun, Nikolay; Michiels, Matthieu; Snyders, Rony

2015-12-01

Possible ways to increase the reliability of time-resolved particle density measurements in pulsed gaseous discharges using resonant absorption spectroscopy are proposed. A special synchronization, called "dynamic source triggering," between a gated detector and two pulsed discharges, one representing the discharge of interest and another being used as a reference source, is developed. An internal digital delay generator in the intensified charge coupled device camera, used at the same time as a detector, is utilized for this purpose. According to the proposed scheme, the light pulses from the reference source follow the gates of detector, passing through the discharge of interest only when necessary. This allows for the utilization of short-pulse plasmas as reference sources, which is critical for time-resolved absorption analysis of strongly emitting pulsed discharges. In addition to dynamic source triggering, the reliability of absorption measurements can be further increased using simultaneous detection of spectra relevant for absorption method, which is also demonstrated in this work. The proposed methods are illustrated by the time-resolved measurements of the metal atom density in a high-power impulse magnetron sputtering (HiPIMS) discharge, using either a hollow cathode lamp or another HiPIMS discharge as a pulsed reference source.

PREFACE: First International Congress of the International Association of Inverse Problems (IPIA): Applied Inverse Problems 2007: Theoretical and Computational Aspects

NASA Astrophysics Data System (ADS)

Uhlmann, Gunther

2008-07-01

This volume represents the proceedings of the fourth Applied Inverse Problems (AIP) international conference and the first congress of the Inverse Problems International Association (IPIA) which was held in Vancouver, Canada, June 25 29, 2007. The organizing committee was formed by Uri Ascher, University of British Columbia, Richard Froese, University of British Columbia, Gary Margrave, University of Calgary, and Gunther Uhlmann, University of Washington, chair. The conference was part of the activities of the Pacific Institute of Mathematical Sciences (PIMS) Collaborative Research Group on inverse problems (http://www.pims.math.ca/scientific/collaborative-research-groups/past-crgs). This event was also supported by grants from NSF and MITACS. Inverse Problems (IP) are problems where causes for a desired or an observed effect are to be determined. They lie at the heart of scientific inquiry and technological development. The enormous increase in computing power and the development of powerful algorithms have made it possible to apply the techniques of IP to real-world problems of growing complexity. Applications include a number of medical as well as other imaging techniques, location of oil and mineral deposits in the earth's substructure, creation of astrophysical images from telescope data, finding cracks and interfaces within materials, shape optimization, model identification in growth processes and, more recently, modelling in the life sciences. The series of Applied Inverse Problems (AIP) Conferences aims to provide a primary international forum for academic and industrial researchers working on all aspects of inverse problems, such as mathematical modelling, functional analytic methods, computational approaches, numerical algorithms etc. The steering committee of the AIP conferences consists of Heinz Engl (Johannes Kepler Universität, Austria), Joyce McLaughlin (RPI, USA), William Rundell (Texas A&M, USA), Erkki Somersalo (Helsinki University of Technology, Finland), Masahiro Yamamoto (University of Tokyo, Japan), Gunther Uhlmann (University of Washington) and Jun Zou (Chinese University of Hong Kong). IPIA is a recently formed organization that intends to promote the field of inverse problem at all levels. See http://www.inverse-problems.net/. IPIA awarded the first Calderón prize at the opening of the conference to Matti Lassas (see first article in the Proceedings). There was also a general meeting of IPIA during the workshop. This was probably the largest conference ever on IP with 350 registered participants. The program consisted of 18 invited speakers and the Calderón Prize Lecture given by Matti Lassas. Another integral part of the program was the more than 60 mini-symposia that covered a broad spectrum of the theory and applications of inverse problems, focusing on recent developments in medical imaging, seismic exploration, remote sensing, industrial applications, numerical and regularization methods in inverse problems. Another important related topic was image processing in particular the advances which have allowed for significant enhancement of widely used imaging techniques. For more details on the program see the web page: http://www.pims.math.ca/science/2007/07aip. These proceedings reflect the broad spectrum of topics covered in AIP 2007. The conference and these proceedings would not have happened without the contributions of many people. I thank all my fellow organizers, the invited speakers, the speakers and organizers of mini-symposia for making this an exciting and vibrant event. I also thank PIMS, NSF and MITACS for their generous financial support. I take this opportunity to thank the PIMS staff, particularly Ken Leung, for making the local arrangements. Also thanks are due to Stephen McDowall for his help in preparing the schedule of the conference and Xiaosheng Li for the help in preparing these proceedings. I also would like to thank the contributors of this volume and the referees. Finally, many thanks are due to Graham Douglas and Elaine Longden-Chapman for suggesting publication in Journal of Physics: Conference Series.

28 CFR 551.60 - Volunteer community service projects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... MANAGEMENT MISCELLANEOUS Volunteer Community Service Projects § 551.60 Volunteer community service projects. (a) A volunteer community service project is a project sponsored and developed by local government or... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Volunteer community service projects. 551...

28 CFR 551.60 - Volunteer community service projects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Volunteer community service projects. 551... MANAGEMENT MISCELLANEOUS Volunteer Community Service Projects § 551.60 Volunteer community service projects. (a) A volunteer community service project is a project sponsored and developed by local government or...

28 CFR 551.60 - Volunteer community service projects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Volunteer community service projects. 551... MANAGEMENT MISCELLANEOUS Volunteer Community Service Projects § 551.60 Volunteer community service projects. (a) A volunteer community service project is a project sponsored and developed by local government or...

28 CFR 551.60 - Volunteer community service projects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Volunteer community service projects. 551... MANAGEMENT MISCELLANEOUS Volunteer Community Service Projects § 551.60 Volunteer community service projects. (a) A volunteer community service project is a project sponsored and developed by local government or...

28 CFR 551.60 - Volunteer community service projects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Volunteer community service projects. 551... MANAGEMENT MISCELLANEOUS Volunteer Community Service Projects § 551.60 Volunteer community service projects. (a) A volunteer community service project is a project sponsored and developed by local government or...

Pond and Irrigation Model (PIM): a tool for simultaneously evaluating pond water availability and crop irrigation demand

Treesearch

Ying Ouyang; Gary Feng; Theodor D. Leininger; John Read; Johnie N. Jenkins

2018-01-01

Agricultural ponds are an important alternative source of water for crop irrigation to conserve surface and ground water resources. In recent years more such ponds have been constructed in Mississippi and around the world. There is currently, however, a lack of a tool to simultaneously estimate crop irrigation demand and pond water availability. In this study, a Pond-...

Hierarchical structures of metal micro- and nanoparticles for PIM

NASA Astrophysics Data System (ADS)

Pervikov, Aleksandr; Rodkevich, Nikolay; Glazkova, Elena; Lerner, Marat

2017-12-01

The design of the metal nanopowder composition to prepare the feedstock for powder injection molding was researched. The treatment of aluminum nanopowders with organic compounds was studied. The organic compounds sorbed on the surface of the nanoparticles was shown to change drastically the physico-mechanical characteristics of the nanopowders. These nanopowders demonstrate enhanced characteristics, in particularly, low reactivity, high compatibility with organic binder for feedstocks.

Pim-1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

DTIC Science & Technology

2005-10-01

Reiter RE, Lilly MB: Gene expression profiling in R- flurbiprofen -treated prostate cancer: Identification of prostate stem cell antigen as a... flurbiprofen -regulated gene. (submitted, 2006). 51. Holder SL, Zemskova M, Bremner R, Neidigh J, Lilly MB: Identification of specific, cell-permeable...profiling in R- flurbiprofen - treated prostate cancer: Identification of prostate stem cell antigen as a flurbiprofen - regulated gene. (poster

Applied Polarography for Analysis of Ordnance Materials. Part 1. Determination and Monitoring for 1,2-Propyleneglycoldinitrate in Effluent Water by Single-Sweep Polarography

DTIC Science & Technology

1976-06-01

ie irom Ott - Ae wastewatt:r. Data obtained by the NWC-developed method of analyds and field equipment ccupare favorably with data obtained by a vapor...5, curve &. A microaliquot of standard PIM solution is then added to the cell solution and the procedure is repeated. This is known as the standard

Association of pre-operative medication use with post-operative delirium in surgical oncology patients receiving comprehensive geriatric assessment.

PubMed

Jeong, Young Mi; Lee, Eunsook; Kim, Kwang-Il; Chung, Jee Eun; In Park, Hae; Lee, Byung Koo; Gwak, Hye Sun

2016-07-07

Older patients undergoing surgery tend to have a higher frequency of delirium. Delirium is strongly associated with poor surgical outcomes. This study evaluated the association between pre-operative medication use and post-operative delirium (POD) in surgical oncology patients receiving comprehensive geriatric assessment (CGA). A total of 475 patients who were scheduled for cancer surgery and received CGA from January 2014 to June 2015 were included. Pre-operative medication review through CGA was conducted on polypharmacy (≥5 medications), delirium-inducing medications (DIMs), fall-inducing medications (FIMs), and potentially inappropriate medications (PIMs). POD was confirmed by psychiatric consultation, and DSM-V criteria were used for diagnosing delirium. The model fit of the prediction model was assessed by computing the Hosmer-Lemeshow goodness-of-fit test. Effect size was measured using the Nagelkerke R(2). Discrimination of the model was assessed by an analysis of the area under receiver operating curve (AUROC). Two models were constructed for multivariate analysis based on univariate analysis; model I included dementia and DIM in addition to age and sex, and model II included PIM instead of DIM of model I. Every one year increase of age increased the risk of POD by about 1.1-fold. DIM was a significant factor for POD after adjusting for confounders (AOR 12.78, 95 % CI 2.83-57.74). PIM was also a significant factor for POD (AOR 5.53, 95 % CI 2.03-15.05). The Hosmer-Lemeshow test results revealed good fits for both models (χ(2) = 3.842, p = 0.871 for model I and χ(2) = 8.130, p = 0.421 for model II). The Nagelkerke R(2) effect size and AUROC for model I was 0.215 and 0.833, respectively. Model II had the Nagelkerke R(2)effect size of 0.174 and AUROC of 0.819. These results suggest that pharmacists' comprehensive review for pre-operative medication use is critical for the post-operative outcomes like delirium in older patients.

Quality of prescribing in community-dwelling elderly patients in France: an observational study in community pharmacies.

PubMed

Bourcier, E; Mille, F; Brunie, V; Korb-Savoldelli, V; Lafortune, C; Buyse, M; Fernandez, C; Hindlet, P

2017-12-01

Background In order to ensure safer prescriptions in the elderly, lists of potentially inappropriate medications (PIMs) and guidelines have been introduced. Whereas the effectiveness of these measures has been well studied in hospitals, data are sparse for the community-dwelling patients. Objective To assess the quality of prescriptions among community-dwelling elderly patients, and potential associations between prescription patterns, patient characteristics and medication adherence. Setting Community pharmacies in France. Method We conducted a prospective observational study between January and June 2013. Patients aged 75 and over coming to the community pharmacy with a prescription from a general practitioner were invited to participate to the study. The compliance of the prescription was assessed with regards to Beers Criteria and French Health Authority guidelines (FHA) for prescription in the elderly, the degree of adherence was assessed with the Girerd score. Main outcome measure Percentage of prescriptions compliant with Beers Criteria and FHA guidelines. Results Among the 1206 prescriptions analysed, 67.49% (n = 814) contained a PIM. Only 12.77% (n = 154) complied with mandatory requirements of the FHA. Prescriptions were ordered by therapeutic field in 51.24% (n = 618) of cases. Dosing regimen was incomplete in 57.21% (n = 690) of prescriptions. Only 29.19% (n = 352) of patients reported no difficulty with regard to adherence (Girerd score = 0). The use of International Non-proprietary Name was associated with an increased risk of nonadherence (adjusted OR = 1.59 [95% CI = 1.13-2.23] and 1.68 [95% CI = 1.12-2.49] respectively). Patient satisfaction with formulation was associated with a lower risk of non-adherence (adjusted OR = 0.63 [95% CI = 0.45-0.90]). Conclusion A substantial proportion of patients are exposed to PIMs and prescriptions that do not comply with the FHA Guidelines. This issue, as well as identified risk factors for non-adherence, should be taken into consideration by general practitioners and community pharmacists when prescribing/dispensing medications to the elderly.

Linear Algebraic Modeling of Power Flow in the HMPT500-3 Transmission

DTIC Science & Technology

2012-08-01

BFV ) family and Multiple Launch Rocket System (MLRS). It is also proposed for use in the Paladin Integrated Management (PIM) self-propelled...howitzer and BFV derived Armored Multipurpose Vehicle (AMPV). Weight growth of these vehicles is exceeding the capacity of the current HMPT500-3...reduce the heat-rejection burden to the cooling system also makes efficiency improvements desirable. Automotive performance models of the BFV to

Linear Algebraic Modeling of Power Flow in the HMP500-3 Transmission

DTIC Science & Technology

2012-08-01

BFV ) family and Multiple Launch Rocket System (MLRS). It is also proposed for use in the Paladin Integrated Management (PIM) self-propelled...howitzer and BFV derived Armored Multipurpose Vehicle (AMPV). Weight growth of these vehicles is exceeding the capacity of the current HMPT500-3...reduce the heat-rejection burden to the cooling system also makes efficiency improvements desirable. Automotive performance models of the BFV to date

High Dynamic Range Nonlinear Measurement using Analog Cancellation

DTIC Science & Technology

2012-10-01

shield around sensitive areas. The target may also be sensitive to radiated coupling from the system and will benefit from a shield box or Faraday ... cage , if it is not already enclosed. On the shared measurement path and through the target, cross-channel coupling cannot be prevented, so low-PIM...testing is desired, traditional filtering is recommended, as the primary benefits of the analog canceller are effectively nullified. 2.4 Wideband

Controlled Studies of Whistler Wave Interactions with Energetic Particles in Radiation Belts

DTIC Science & Technology

2009-07-01

the IGRF geomagnetic field and PIM ionosphere /plasmasphere models . Those simulations demonstrate that on this particular evening 28.5 kHz whistler...a simplified slab model of ionospheric plasmas, we can compute the transmission coefficient and, subsequently, estimate that -15% of the incident...with inner radiation belts as well as the ionospheric effects caused by precipitated energetic electrons. The whistler waves used in our experiments

Intramolecular Dynamics: A Study of Molecules at High Levels of Vibrational Excitation.

DTIC Science & Technology

1988-05-27

aareemlent stith the photoa.couxueC rexults.,I4 % obintied t r iii pfii ioaCOI it tic tveaxu retntsx." Si ne thle xhoxs xthat Iii the I ott fi nence...t 0 200 400 ns 6000 between pump and probe pulse for CH3 CHF2 at 660 Pa. Infrared excitation: 10.6 pim P(20) line, 0.5 ns pulse with average fluence

Validation of a novel attentional bias modification task: the future may be in the cards.

PubMed

Notebaert, Lies; Clarke, Patrick J F; Grafton, Ben; MacLeod, Colin

2015-02-01

Attentional bias modification (ABM) is a promising therapeutic tool aimed at changing patterns of attentional selectivity associated with heightened anxiety. A number of studies have successfully implemented ABM using the modified dot-probe task. However others have not achieved the attentional change required to achieve emotional benefits, highlighting the need for new ABM methods. The current study compared the effectiveness of a newly developed ABM task against the traditional dot-probe ABM task. The new person-identity-matching (PIM) task presented participants with virtual cards, each depicting a happy and angry person. The task encourages selective attention toward or away from threat by requiring participants to make matching judgements between two cards, based either on the identities of the happy faces, or of the angry faces. Change in attentional bias achieved by both ABM tasks was measured by a dot-probe assessment task. Their impact on emotional vulnerability was assessed by measuring negative emotional reactions to a video stressor. The PIM task succeeded in modifying attentional bias, and exerting an impact on emotional reactivity, whereas this was not the case for the dot-probe task. These results are considered in relation to the potential clinical utility of the current task in comparison to traditional ABM methodologies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simultaneous electrical and optical study of spoke rotation, merging and splitting in HiPIMS plasma

NASA Astrophysics Data System (ADS)

Klein, P.; Lockwood Estrin, F.; Hnilica, J.; Vašina, P.; Bradley, J. W.

2017-01-01

To gain more information on the temporal and spatial behaviour of self-organized spoke structures in HiPIMS plasmas, a correlation between the broadband optical image of an individual spoke (taken over 200 ns) and the current it delivers to the target has been made for a range of magnetron operating conditions. As a spoke passes over a set of embedded probes in the niobium cathode target, a distinct modulation in the local current density is observed, (typically up to twice the average value), matching very well the radially integrated optical emission intensities (obtained remotely with an ICCD camera). The dual diagnostic system allows the merging and splitting of a set of spokes to be studied as they rotate. It is observed that in the merger of two spokes, the trailing spoke maintains its velocity while the leading spoke either decreases its velocity or increases its azimuthal length. In the spoke splitting process, the total charge collected by an embedded probe is conserved. A simple phenomenological model is developed that relates the spoke mode number m to the spoke dimensions, spoke velocity and gas atom velocity. The results are discussed in the context of the observations of spoke dynamics made by Hecimovic et al (2015 Plasma Sources Sci. Technol. 24 045005)

Innovative Approach for Developing Spacecraft Interior Acoustic Requirement Allocation

NASA Technical Reports Server (NTRS)

Chu, S. Reynold; Dandaroy, Indranil; Allen, Christopher S.

2016-01-01

The Orion Multi-Purpose Crew Vehicle (MPCV) is an American spacecraft for carrying four astronauts during deep space missions. This paper describes an innovative application of Power Injection Method (PIM) for allocating Orion cabin continuous noise Sound Pressure Level (SPL) limits to the sound power level (PWL) limits of major noise sources in the Environmental Control and Life Support System (ECLSS) during all mission phases. PIM is simulated using both Statistical Energy Analysis (SEA) and Hybrid Statistical Energy Analysis-Finite Element (SEA-FE) models of the Orion MPCV to obtain the transfer matrix from the PWL of the noise sources to the acoustic energies of the receivers, i.e., the cavities associated with the cabin habitable volume. The goal of the allocation strategy is to control the total energy of cabin habitable volume for maintaining the required SPL limits. Simulations are used to demonstrate that applying the allocated PWLs to the noise sources in the models indeed reproduces the SPL limits in the habitable volume. The effects of Noise Control Treatment (NCT) on allocated noise source PWLs are investigated. The measurement of source PWLs of involved fan and pump development units are also discussed as it is related to some case-specific details of the allocation strategy discussed here.

Reactive high power impulse magnetron sputtering

NASA Astrophysics Data System (ADS)

Gudmundsson, J. T.; Magnus, F.; Tryggvason, T. K.; Sveinsson, O. B.; Olafsson, S.

2012-10-01

Here we discuss reactive high power impulse magnetron sputtering sputtering (HiPIMS) [1] of Ti target in an Ar/N2 and Ar/O2 atmosphere. The discharge current waveform is highly dependent on both the pulse repetition frequency and discharge voltage. The discharge current increases with decreasing frequency or voltage. This we attribute to an increase in the secondary electron emission yield during the self-sputtering phase of the pulse, as nitride [2] or oxide [3] forms on the target. We also discuss the growth of TiN films on SiO2 at temperatures of 22-600 ^oC. The HiPIMS process produces denser films at lower growth temperature and the surface is much smoother and have a significantly lower resistivity than dc magnetron sputtered films on SiO2 at all growth temperatures due to reduced grain boundary scattering [4].[4pt] [1] J. T. Gudmundsson, N. Brenning, D. Lundin and U. Helmersson, J. Vac. Sci. Technol. A, 30 030801 (2012)[0pt] [2] F. Magnus, O. B. Sveinsson, S. Olafsson and J. T. Gudmundsson, J. Appl. Phys., 110 083306 (2011)[0pt] [3] F. Magnus, T. K. Tryggvason, S. Olafsson and J. T. Gudmundsson, J. Vac. Sci. Technol., submitted 2012[0pt] [4] F. Magnus, A. S. Ingason, S. Olafsson and J. T. Gudmundsson, IEEE Elec. Dev. Lett., accepted 2012

Advancements of labelled radio-pharmaceutics imaging with the PIM-MPGD

NASA Astrophysics Data System (ADS)

Donnard, J.; Arlicot, N.; Berny, R.; Carduner, H.; Leray, P.; Morteau, E.; Servagent, N.; Thers, D.

2009-11-01

The Beta autoradiography is widely used in pharmacology or in biological fields to study the response of an organism to a certain kind of molecule. The image of the distribution is processed by studying the concentration of the radioactivity into different organs. We report on the development of an integrated apparatus based on a PIM device (Parallel Ionization Multiplier) able to process the image of 10 microscope slides at the same time over an area of 18*18 cm2. Thanks to a vacuum pump and a regulation gas circuit, 5 minutes is sufficient to begin an acquisition. All the electronics and the gas distribution are included in the structure leading to a transportable device. Special software has been developed to process data in real time with image visualization. Biological samples can be labelled with β emitters of low energy like 3H/14C or Auger electrons of 125I/99mTc. The measured spatial resolution is 30 μm in 3H and the trigger and the charge rate are constant over more than 6 days of acquisition showing good stability of the device. Moreover, collaboration with doctors and biologists of INSERM (National Institute for Medical Research in France) has started in order to demonstrate that MPGD's can be easily proposed outside a physics laboratory.

Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis.

PubMed

Huang, Xiao X; McCaughan, Geoffrey W; Shackel, Nicholas A; Gorrell, Mark D

2007-09-01

Cirrhosis can lead to hepatocellular carcinoma (HCC). Non-diseased liver and hepatitis C virus (HCV)-associated cirrhosis with or without HCC were compared. Proliferation pathway genes, immune response genes and oncogenes were analysed by a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining. Real-time RT-PCR showed up-regulation of genes in HCV cirrhosis including the proliferation-associated genes bone morphogenetic protein 3 (BMP3), placental growth factor 3 (PGF3), vascular endothelial growth factor receptor 1 (VEGFR1) and soluble VEGFR1, the oncogene FYN, and the immune response-associated genes toll-like receptor 9 (TLR9) and natural killer cell transcript 4 (NK4). Expressions of TLR2 and the oncogenes B-cell CLL/lymphoma 9 (BCL9) and PIM2 were decreased in HCV cirrhosis. In addition, PIM2 and TLR2 were increased in HCV cirrhosis with HCC compared with HCV cirrhosis. The ligand/receptor pair PGF and VEGFR1 was intensely expressed by the portal tract vascular endothelium. VEGFR1 was expressed in reactive biliary epithelial structures in fibrotic septum and in some stellate cells and macrophages. PGF and VEGFR1 may have an important role in the pathogenesis of the neovascular response in cirrhosis.

Project Panama: An International Service Project

ERIC Educational Resources Information Center

Aydlett, Lydia; Randolph, Mickey; Wells, Gayle

2010-01-01

Participation in service learning projects is a growing phenomenon at universities and colleges. Research indicates service projects are beneficial for college students and adults. There is little data investigating developmental differences in how younger versus older participants perceive the service learning process. In this project, older…

Process Integrated Mechanism for Human-Computer Collaboration and Coordination

DTIC Science & Technology

2012-09-12

system we implemented the TAFLib library that provides the communication with TAF . The data received from the TAF server is collected in a data structure...send new commands and flight plans for the UAVs to the TAF server. Test scenarios Several scenarios have been implemented to test and prove our...areas. Shooting Enemies The basic scenario proved the successful integration of PIM and the TAF simulation environment. Subsequently we improved the CP

Development of Monitors for Assessing Exposure of Military Personnel to Toxic Chemicals.

DTIC Science & Technology

2000-01-01

Residues " S ampler Preparation 7 Transfer and Analysis 7 Temperature Effects on PIMS Sampling Rate 8 Environmental Air Sampling 8 Results and...of exposure and potential toxicity to personnel. While progress has been made in improving active water and air sampling technology, such devices...streams, 3) the apparatus is also applicable for use in air sampling deployments in indoor and outdoor scenarios, and 4) the apparatus is commercially

A Tactical Database for the Low Cost Combat Direction System

DTIC Science & Technology

1990-12-01

another object. Track is a representation of some environmental phenomena converted into accurate estimates of geographical position with respect to...by the method CALCULATE RELATIVE POSITION. In order to obtain a better similarity of mehods , the methods OWNSHIP DISTANCE TO PIM, ESTIMATED TIME OF...this mechanism entails the risk that the user will lose all of the work that was done if conflicts are detected and the transaction cannot be committed

SAMS Acceleration Measurements on MIR

NASA Technical Reports Server (NTRS)

Moskowitz, Milton E.; Hrovat, Kenneth; Finkelstein, Robert; Reckart, Timothy

1997-01-01

During NASA Increment 3 (September 1996 to January 1997), about 5 gigabytes of acceleration data were collected by the Space Acceleration Measurement System (SAMS) onboard the Russian Space Station, Mir. The data were recorded on 11 optical disks and were returned to Earth on STS-81. During this time, SAMS data were collected in the Priroda module to support the following experiments: the Mir Structural Dynamics Experiment (MiSDE) and Binary Colloidal Alloy Tests (BCAT). This report points out some of the salient features of the microgravity environment to which these experiments were exposed. Also documented are mission events of interest such as the docked phase of STS-81 operations, a Progress engine burn, attitude control thruster operation, and crew exercise. Also included are a description of the Mir module orientations, and the panel notations within the modules. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. Variations in the acceleration environment caused by unique activities such as crew exercise and life-support fans are presented. The analyses included herein complement those presented in previous mission summary reports published by the Principal Investigator Microgravity Services (PIMS) group.

SAMS Acceleration Measurements on Mir (NASA Increment 4)

NASA Technical Reports Server (NTRS)

DeLombard, Richard

1998-01-01

During NASA Increment 4 (January to May 1997), about 5 gigabytes of acceleration data were collected by the Space Acceleration Measurements System (SAMS) onboard the Russian Space Station, Mir. The data were recorded on 28 optical disks which were returned to Earth on STS-84. During this increment, SAMS data were collected in the Priroda module to support the Mir Structural Dynamics Experiment (MiSDE), the Binary Colloidal Alloy Tests (BCAT), Angular Liquid Bridge (ALB), Candle Flames in Microgravity (CFM), Diffusion Controlled Apparatus Module (DCAM), Enhanced Dynamic Load Sensors (EDLS), Forced Flow Flame Spreading Test (FFFr), Liquid Metal Diffusion (LMD), Protein Crystal Growth in Dewar (PCG/Dewar), Queen's University Experiments in Liquid Diffusion (QUELD), and Technical Evaluation of MIM (TEM). This report points out some of the salient features of the microgravity environment to which these experiments were exposed. Also documented are mission events of interest such as the docked phase of STS-84 operations, a Progress engine bum, Soyuz vehicle docking and undocking, and Progress vehicle docking. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. The analyses included herein complement those presented in previous summary reports prepared by the Principal Investigator Microgravity Services (PIMS) group.

Effectiveness of adjunctive antimicrobial photodynamic therapy in reducing peri-implant inflammatory response in individuals vaping electronic cigarettes: A randomized controlled clinical trial.

PubMed

Al Rifaiy, Mohammed Q; Qutub, Osama A; Alasqah, Mohammed N; Al-Sowygh, Zeyad H; Mokeem, Sameer A; Alrahlah, Ali

2018-06-01

There are no studies that have assessed the effectiveness of antimicrobial photodynamic therapy (aPDT) in reducing peri-implant inflammatory response in individuals vaping electronic cigarettes (e-cigs). This study explored the effectiveness of aPDT as an adjunct to mechanical debridement (MD) in the treatment of peri-implant mucositis (p-iM) in individuals vaping e-cigs. Vaping individuals with p-iM were divided into 2 groups: (a) Group-I: receiving MD with aPDT (test group); and (b) Group-II: MD only (control group). Peri-implant inflammatory parameters including plaque index (PI), bleeding on probing (BoP), and pocket depth (PD) were assessed at baseline and 12-weeks follow-up. Inter- and intra-group comparisons were made using Mann-Whitney U test and Wilcoxon signed ranks test. P-value < 0.05 was considered significant. Thirty-eight male patients (20 in Group-I and 18 in Group-II) were included. The mean age of vaping individuals in groups I and II were 33.6 ± 2.8 and 35.4 ± 2.1 years, respectively. Mean daily frequency of vaping e-cigs in groups I and II was 7.3 ± 0.9 and 5.9 ± 1.0 whereas mean duration of vaping e-cigs was 4.8 ± 1.5 and 4.1 ± 1.3 years respectively. There was no significant difference between groups at baseline. There was significant improvement in PI (p < 0.001) and PD (p < 0.001) at 12-weeks follow-up with respect to the baseline visit in both groups. There was a significant reduction in PI (p < 0.001) and PD (p < 0.001) for group-I as compared to group-II at follow-up. There was no statistically significant difference for BoP between groups at follow-up. Antimicrobial PDT is more effective compared to MD alone in the treatment of p-iM in individuals vaping e-cigs. The findings of the present study should be considered preliminary and interpreted with caution. Further randomized clinical trials should be performed in order to obtain strong conclusions. Copyright © 2018 Elsevier B.V. All rights reserved.

In Situ Investigation of Sea Surface Noise from a Depth of One Meter

DTIC Science & Technology

1989-12-01

photograph was taken corresponds to the point on the oscillogram below the center of the bubble. Chapter 1, Figure 2...instrument, it is surprisingly easy to bury oneself in the minutiae of technical details and lose focus of the ultimate goal. Thus, I will be forever...1) viscosity of the surrounding liquid, especially for bubbles smaller than 3 pim; 2) thermal radiation, which dominates bubbles from about 3 4am to

Joint Center for Operational Analysis Journal. Volume 9, Issue 2, June 2007

DTIC Science & Technology

2007-06-01

black market . • Pakistan Institute of Medical Sciences (PIMS) complained that we did more harm than good by evacuating patients to their hospitals...pharmacies and created a pharmaceutical black market in the local towns. • Local Pakistan physicians lost patients. • Local Pakistan physicians and...geology.com/news/2005/09/ atlantic-ocean-tsunami-threat.html Auf Der Heide, E. (2002). “ Principles of hospital disaster planning;” in Hogan D.E. and

Theoretical Studies of Low-Loss Optical Fibers.

DTIC Science & Technology

1980-09-15

on the fiber surface. Single-mode fiber operation is of interest in communications. Marcuse has shown that surface imperfections are a strong source...0.01 very small value of a : 8A at X = 1 vim Marcuse single mode 2.7 typical value of a = 1 jim, A : 10.6 vm, af = 37 Pim surface imperfections 55...Braunstein, "Scattering Losses in Single and Polycrystalline Materials for Infrared Fiber Applications," unpublished. 5. D. Marcuse , "Mode Conversion

Utilization of Activated Carbon Prepared from Aceh Coffee Grounds as Bio-sorbent for Treatment of Fertilizer Industrial Waste Water

NASA Astrophysics Data System (ADS)

Mariana, M.; Mahidin, M.; Mulana, F.; Aman, F.

2018-05-01

The people of Aceh are well known as coffee drinkers. Therefore, a lot of coffee shops have been established in Aceh in the past decade. The growing of coffee shops resulting to large amounts of coffee waste produced in Aceh Province that will become solid waste if not wisely utilized. The high carbon content in coffee underlined as background of this research to be utilized those used coffee grounds as bio-sorbent. The preparation of activated carbon from coffee grounds by using carbonization method that was initially activated with HCl was expected to increase the absorption capacity. The prepared activated carbon with high reactivity was applied to adsorb nitrite, nitrate and ammonia in wastewater outlet of PT. PIM wastewater pond. Morphological structure of coffee waste was analyzed by using Scanning Electron Microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The result showed that the adsorption capacity of iodine was equal to 856.578 mg/g. From the characterization results, it was concluded that the activated carbon from coffee waste complied to the permitted quality standards in accordance with the quality requirements of activated carbon SNI No. 06-3730-1995. Observed from the adsorption efficiency, the bio-sorbent showed a tendency of adsorbing more ammonia than nitrite and nitrate of PT. PIM wastewater with ammonia absorption efficiency of 56%.

Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.

PubMed

Hoefnagel, Juliette J; Dijkman, Remco; Basso, Katia; Jansen, Patty M; Hallermann, Christian; Willemze, Rein; Tensen, Cornelis P; Vermeer, Maarten H

2005-05-01

In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.

2.5-year-olds use cross-situational consistency to learn verbs under referential uncertainty.

PubMed

Scott, Rose M; Fisher, Cynthia

2012-02-01

Recent evidence shows that children can use cross-situational statistics to learn new object labels under referential ambiguity (e.g., Smith & Yu, 2008). Such evidence has been interpreted as support for proposals that statistical information about word-referent co-occurrence plays a powerful role in word learning. But object labels represent only a fraction of the vocabulary children acquire, and arguably represent the simplest case of word learning based on observations of world scenes. Here we extended the study of cross-situational word learning to a new segment of the vocabulary, action verbs, to permit a stronger test of the role of statistical information in word learning. In two experiments, on each trial 2.5-year-olds encountered two novel intransitive (e.g., "She's pimming!"; Experiment 1) or transitive verbs (e.g., "She's pimming her toy!"; Experiment 2) while viewing two action events. The consistency with which each verb accompanied each action provided the only source of information about the intended referent of each verb. The 2.5-year-olds used cross-situational consistency in verb learning, but also showed significant limits on their ability to do so as the sentences and scenes became slightly more complex. These findings help to define the role of cross-situational observation in word learning. Copyright © 2011 Elsevier B.V. All rights reserved.

2.5-year-olds use cross-situational consistency to learn verbs under referential uncertainty

PubMed Central

Scott, Rose M.; Fisher, Cynthia

2011-01-01

Recent evidence shows that children can use cross-situational statistics to learn new object labels under referential ambiguity (e.g., Smith & Yu, 2008). Such evidence has been interpreted as support for proposals that statistical information about word-referent co-occurrence plays a powerful role in word learning. But object labels represent only a fraction of the vocabulary children acquire, and arguably represent the simplest case of word learning based on observations of world scenes. Here we extended the study of cross-situational word learning to a new segment of the vocabulary, action verbs, to permit a stronger test of the role of statistical information in word learning. In two experiments, on each trial 2.5-year-olds encountered two novel intransitive (e.g., “She’s pimming!”; Experiment 1) or transitive verbs (e.g., “She’s pimming her toy!”; Experiment 2) while viewing two action events. The consistency with which each verb accompanied each action provided the only source of information about the intended referent of each verb. The 2.5-year-olds used cross-situational consistency in verb learning, but also showed significant limits on their ability to do so as the sentences and scenes became slightly more complex. These findings help to define the role of cross-situational observation in word learning. PMID:22104489

Effect of dopants on the soft magnetic properties and high frequency characteristics of FeCoBM (M = Ti, Nb, Hf, and Ta) thin films.

PubMed

Hsieh, C C; Lin, T H; Chang, H W; Chang, C W; Chang, W C; Yang, C C

2011-03-01

Effect of dopants on the soft magnetic properties and high frequency characteristics of FeCoBM thin films (M = Ti, Nb, Hf, and Ta) have been studied. For (Fe0.55Co0.45)(100-x)B(x) (x = 5-15) thin films, with the increase of B content, the resistivity was increased because B could decrease the crystallinity of the films. The (Fe0.55Co0.45)90B10 thin film showed the optimum properties, where 4piM(s) = 16.1 kG, H(ce) = 64.2 Oe, H(ch) = 13.5 Oe, H(k) = 310 Oe and p = 338 microomega-cm. To reduce the coercivity of the film, the elements M, including Ti, Nb, Hf, and Ta, were selected to substitute for B in the FeCoB films. It was found that (Fe0.55Co0.45)90B6Ti2Nb2 thin film after annealing at a temperature of 200 degrees C for 30 min showed the optimal properties, where 4piM(s) = 15.8 kG, H(ce) = 4.8 Oe, H(ch) = 3.6 Oe, H(k) = 224 Oe and p = 290 microomega-cm. The theoretically calculated ferromagnetic resonance frequency of the developed films can be higher than 5 GHz.

An Academic Club Service Learning Project as a Demonstration of Experiential Teaching Tools

ERIC Educational Resources Information Center

Bonczek, James L.; Snyder, Lori Unruh; Ellis, Larry R.

2007-01-01

We describe our pedagogical approaches and experiences with an academic club service learning project (one semester, 20 club participants, including both graduate students and lower and upper-level undergraduates). Our service learning project responds to the recent demand for more community service-based club projects within the College of…

34 CFR 645.15 - What additional services may Veterans Upward Bound projects provide?

Code of Federal Regulations, 2013 CFR

2013-07-01

... projects provide? 645.15 Section 645.15 Education Regulations of the Offices of the Department of Education... Projects and Services Does the Secretary Assist Under This Program? § 645.15 What additional services may Veterans Upward Bound projects provide? In addition to the services that must be provided under § 645.11, a...

34 CFR 645.15 - What additional services may Veterans Upward Bound projects provide?

Code of Federal Regulations, 2014 CFR

2014-07-01

... projects provide? 645.15 Section 645.15 Education Regulations of the Offices of the Department of Education... Projects and Services Does the Secretary Assist Under This Program? § 645.15 What additional services may Veterans Upward Bound projects provide? In addition to the services that must be provided under § 645.11, a...

34 CFR 645.15 - What additional services may Veterans Upward Bound projects provide?

Code of Federal Regulations, 2012 CFR

2012-07-01

... projects provide? 645.15 Section 645.15 Education Regulations of the Offices of the Department of Education... Projects and Services Does the Secretary Assist Under This Program? § 645.15 What additional services may Veterans Upward Bound projects provide? In addition to the services that must be provided under § 645.11, a...

Oregon Project for Services to Children and Youth with Deaf-Blindness. Final Performance Report.

ERIC Educational Resources Information Center

Otos, Maurine

This report describes activities and accomplishments of the Oregon Project for Services to Children and Youth with Deaf-Blindness, a 3-year federally supported project to ensure effective educational services for this population and provide support for families and service providers. The project focused on: (1) identifying additional children with…

The Indiana Deafblind Services Project: Services for Children with Deafblindness Program. Final Performance Report.

ERIC Educational Resources Information Center

Indiana State Univ., Terre Haute. Blumberg Center for Interdisciplinary Studies in Special Education.

This final report describes activities and accomplishments of the Indiana Deaf-Blind Services Project, a 4-year federally funded project to enhance and further develop coordinated direct services to children and youth, birth through 2 and ages 18 through 21. The project also was designed to provide technical assistance to public and private…

34 CFR 645.15 - What additional services may Veterans Upward Bound projects provide?

Code of Federal Regulations, 2011 CFR

2011-07-01

... projects provide? 645.15 Section 645.15 Education Regulations of the Offices of the Department of Education... Projects and Services Does the Secretary Assist Under This Program? § 645.15 What additional services may Veterans Upward Bound projects provide? In addition to the services that must be provided under § 645.11, a...

Wall-slip of highly filled powder injection molding compounds: Effect of flow channel geometry and roughness

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

Hausnerova, Berenika; Sanetrnik, Daniel; Paravanova, Gordana

2014-05-15

The paper deals with the rheological behavior of highly filled compounds proceeded via powder injection molding (PIM) and applied in many sectors of industry (automotive, medicine, electronic or military). Online rheometer equipped with slit dies varying in surface roughness and dimensions was applied to investigate the wall-slip as a rheological phenomenon, which can be considered as a parameter indicating the separation of compound components (polymer binder and metallic powder) during high shear rates when injection molded.

Solid State Research.

DTIC Science & Technology

1984-11-15

Coupling to Surface Plasma Waves 20 2.3 Theory of the Effect of Traps on the Spectral Charac- teristics of Diode Lasers 23 3 . MATERIALS RESEARCH 27...Page 1-1(a) Schematic Cross Section of InGaAs PSIN Structure. Gap Spac- ing (d) Is 3 , 5, 10, or 20 pm. 2 1-1(b) Curve Tracer I-V Characteristics of a...20-pim PSIN Device in Dark and Under Illumination 2 1-2 Pulse Response of a 3 -#Am PSIN Device, Under Forward and Reverse Bias. to a Comb-Generator

Wall-slip of highly filled powder injection molding compounds: Effect of flow channel geometry and roughness

NASA Astrophysics Data System (ADS)

Hausnerova, Berenika; Sanetrnik, Daniel; Paravanova, Gordana

2014-05-01

The paper deals with the rheological behavior of highly filled compounds proceeded via powder injection molding (PIM) and applied in many sectors of industry (automotive, medicine, electronic or military). Online rheometer equipped with slit dies varying in surface roughness and dimensions was applied to investigate the wall-slip as a rheological phenomenon, which can be considered as a parameter indicating the separation of compound components (polymer binder and metallic powder) during high shear rates when injection molded.

A Novel Approach for a Low-Cost Deployable Antenna

NASA Technical Reports Server (NTRS)

Amend, Chris; Nurnberger, Michael; Oppenheimer, Paul; Koss, Steve; Purdy, Bill

2010-01-01

The Naval Research Laboratory (NRL) has designed, built, and fully qualified a low cost, low Passive Intermodulation (PIM) 12-foot (3.66-m) diameter deployable ultra high frequency (UHF) antenna for the Tacsat-4 program. The design utilized novel approaches in reflector material and capacitive coupling techniques. This paper discusses major design trades, unique design characteristics, and lessons learned from the development of the Tacsat 4 deployable antenna. This antenna development was sponsored by the Office of Naval Research.

Aids to navigation service force mix 2000 project. Volume 1 : development and application of an aids to navigation service force mix decision support system

DOT National Transportation Integrated Search

1992-07-01

The Aids to Navigation (ATON) Service Force Mix (SFM) 2000 Project is documented in a Project Overview and three separately bound volumes. This is the Project Overview. The Project Overview describes the purpose, approach, analysis, and results of th...

Funding Mechanisms for Ecosystem Services Projects

NASA Astrophysics Data System (ADS)

Russell, V.

2014-12-01

Ecosystem services projects ideally should be funded through commoditized markets. Where those markets do not exist financing directly from interested private sector parties can be a direct link between business interested in fulfilling sustainability goals and project implementers. Challenges exist, however in 1) linking those interests; 2) carefully quantifying the services produced, their true costs to implement and meeting protocol standards; 3) measuring the success of projects, especially over lengthy periods of time; and 4) balancing issues related to multiple spatial scales for projects and funding to make a difference. Examples from National Forest Foundation's experience implementing carbon and water projects with multiple private sector funders and the USDA Forest Service will highlight experiences and lessons learned in funding and implementing ecosystem service projects.

Learning from Experience: A Collection of Service-Learning Projects Linking Academic Standards to Curriculum.

ERIC Educational Resources Information Center

Babcock, Barbara, Ed.

Service-learning projects combine community service with student learning in a practical way that enhances academic knowledge and improves community environments and fellowship. This compilation is designed to show the service-learning process in action. The collection presents outstanding examples of successful service-learning projects as…

An Exploratory Study of Risk Factors for Implementing Service-Oriented IS Projects

NASA Astrophysics Data System (ADS)

Chang, Hsin-Lu; Lue, Chia-Pei

For IS project managers, how to implement the projects successfully is always a challenge. Further, as more and more enterprises start to develop service-oriented IS projects, it is essential to assess the sources and impacts of relevant risks. This research aimed at identifying risk factors related to service-oriented IS projects and analyzing the impact of these risk factors. Applying the SIMM (service integrated maturity model) proposed by IBM, customer service systems were selected to justify the research framework. Result showed that the risk factors influencing the adoption of service-oriented systems were insufficient technology planning, lack of expertise, ineffective project governance, and organizational misalignment, listed in the order of strength of influence. The findings of this research is expected to assist managers realize the risks and the importance of these risks that have to be noticed and controlled when making decisions on service-oriented systems adoption.

49 CFR 633.19 - Financing the PMO program.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF TRANSPORTATION PROJECT MANAGEMENT OVERSIGHT Project Management Oversight Services § 633.19... or entity to provide a project management oversight service in connection with a major capital... project management oversight services under this part will provide for the payment by FTA of 100 percent...

49 CFR 633.19 - Financing the PMO program.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF TRANSPORTATION PROJECT MANAGEMENT OVERSIGHT Project Management Oversight Services § 633.19... or entity to provide a project management oversight service in connection with a major capital... project management oversight services under this part will provide for the payment by FTA of 100 percent...

49 CFR 633.19 - Financing the PMO program.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF TRANSPORTATION PROJECT MANAGEMENT OVERSIGHT Project Management Oversight Services § 633.19... or entity to provide a project management oversight service in connection with a major capital... project management oversight services under this part will provide for the payment by FTA of 100 percent...

49 CFR 633.19 - Financing the PMO program.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF TRANSPORTATION PROJECT MANAGEMENT OVERSIGHT Project Management Oversight Services § 633.19... or entity to provide a project management oversight service in connection with a major capital... project management oversight services under this part will provide for the payment by FTA of 100 percent...

49 CFR 633.19 - Financing the PMO program.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF TRANSPORTATION PROJECT MANAGEMENT OVERSIGHT Project Management Oversight Services § 633.19... or entity to provide a project management oversight service in connection with a major capital... project management oversight services under this part will provide for the payment by FTA of 100 percent...

SISGR - Hydrogen Caged in Carbon-Exploration of Novel Carbon-Hydrogen Interactions

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

Lueking, Angela; Badding, John; Crespi, Vinent

Hydrogen trapped in a carbon cage, captured through repulsive interactions, is a novel concept in hydrogen storage. Trapping hydrogen via repulsive interactions borrows an idea from macroscale hydrogen storage (i.e. compressed gas storage tanks) and reapplies these concepts on the nanoscale in specially designed molecular containers. Under extreme conditions of pressure, hydrogen solubility in carbon materials is expected to increase and carbon is expected to restructure to minimize volume via a mixed sp2/sp3 hydrogenated state. Thermodynamics dictate that pre-formed C-H structures will rearrange with increased pressure, yet the final carbon-hydrogen interactions may be dependent upon the mechanism by which hydrogenmore » is introduced. Gas “trapping” is meant to denote gas present in a solid in a high density, adsorbed-like state, when the external pressure is much less than that necessary to provide a comparable fluid density. Trapping thus denotes a kinetically metastable state rather than thermodynamic equilibrium. This project probed mechanochemical means to polymerize select hydrocarbons in the presence of gases, in an attempt to form localized carbon cages that trap gases via repulsive interactions. Aromatic, polyaromatic, and hydroaromatic molecules expected to undergo cyclo-addition reactions were polymerized at high (~GPa) pressures to form extended hydrogenated amorphous carbon networks. Notably, aromatics with a pre-existing internal free volume (such as Triptycene) appeared to retain an internal porosity upon application of pressure. However, a high photoluminescence background after polymerization precluded in situ identification of trapped gases. No spectroscopic evidence was found after depressurization that would be indicative of pockets of trapped gases in a localized high-pressure environment. Control studies suggested this measurement may be insensitive to gases at low pressure. Similarly, no spectral fingerprint was found for gas-imbued spherical carbon nanoshells, even after chemical “capping” of the gas-imbued nanoshells to limit gas diffusivity. Subsequently, spectral probes of gas vibrational modes adsorbed in various carbon nanostructures (including activated carbons, single-wall carbon nanotubes, polymers of intrinsic microporosity (PIMs), and UV-irradiated PIMs with decreased pore size) were found only at high pressure. The vibrational mode of the adsorbed film became perturbed in high density films, and the perturbation was sensitive to surface functional groups, pore size, and pore dimension. Experimental results were corroborated with first-principle modeling using density functional theory. Development of semi-empirical correlations that relate the spectral features to pore dimension, geometry, and chemical potential of the adsorbed film are on-going.« less

Community Based Demonstration Projects: Willamette Ecosystem Services Project (WESP)

EPA Science Inventory

EPA’s Ecosystem Services Research Program in the Office of Research and Development is focused on the study of ecosystem services and the benefits to human well-being provided by ecological systems. As part of this research effort, the Willamette Ecosystems Services Project (WE...

76 FR 19753 - Applications for New Awards; Vocational Rehabilitation Services Projects for American Indians...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-08

... DEPARTMENT OF EDUCATION Applications for New Awards; Vocational Rehabilitation Services Projects..., Department of Education. ACTION: Notice. Overview Information Vocational Rehabilitation Services Projects for... vocational rehabilitation (VR) services to American Indians with disabilities who reside on or near Federal...

Did Project Liberty displace community-based medicaid services in New York?

PubMed

Gomes, Carla; McGuire, Thomas G; Foster, M Jameson; Donahue, Sheila A; Felton, Chip J; Essock, Susan M

2006-09-01

This study analyzed how the introduction of Project Liberty services after the September 11, 2001, terrorist attacks affected agencies' provision of community-based Medicaid mental health services in the New York metropolitan area. Provision of Medicaid mental health services was tracked between January 2000 and June 2003 for provider agencies participating in Project Liberty (N=164) and for a comparison group of mental health provider agencies that did not participate in this program (N=94). Overall, participation in Project Liberty did not significantly affect the volume of Medicaid services provided. However, for agencies with one site, a statistically significant difference was seen; compared with agencies in the comparison group, agencies that participated in Project Liberty claimed a mean+/-SE decrease of $4.66+/-3.57 less in Medicaid services per month per Project Liberty visit. Project Liberty permitted rapid expansion of the total volume of services provided by community-based organizations without interfering with the provision of traditional services, although a modest effect was seen for smaller agencies. Although the results do not imply that "supply side" planning for disaster needs would not improve system response, they do imply that implementation of flexible "demand side" financing can call forth a large volume of new services rapidly and without interfering with other community services.

Implementing service improvement projects within pre-registration nursing education: a multi-method case study evaluation.

PubMed

Baillie, Lesley; Bromley, Barbara; Walker, Moira; Jones, Rebecca; Mhlanga, Fortune

2014-01-01

Preparing healthcare students for quality and service improvement is important internationally. A United Kingdom (UK) initiative aims to embed service improvement in pre-registration education. A UK university implemented service improvement teaching for all nursing students. In addition, the degree pathway students conducted service improvement projects as the basis for their dissertations. The study aimed to evaluate the implementation of service improvement projects within a pre-registration nursing curriculum. A multi-method case study was conducted, using student questionnaires, focus groups with students and academic staff, and observation of action learning sets. Questionnaire data were analysed using SPSS v19. Qualitative data were analysed using Ritchie and Spencer's (1994) Framework Approach. Students were very positive about service improvement. The degree students, who conducted service improvement projects in practice, felt more knowledgeable than advanced diploma students. Selecting the project focus was a key issue and students encountered some challenges in practice. Support for student service improvement projects came from action learning sets, placement staff, and academic staff. Service improvement projects had a positive effect on students' learning. An effective partnership between the university and partner healthcare organisations, and support for students in practice, is essential. Copyright © 2013 Elsevier Ltd. All rights reserved.

77 FR 8328 - Open Meeting of the Taxpayer Advocacy Panel Face-to-Face Service Methods Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... Face-to-Face Service Methods Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Face-to-Face Service Methods... Panel Face-to-Face Service Methods Project Committee will be held Tuesday, March 13, 2012, at 2 p.m...

77 FR 61053 - Open Meeting of the Taxpayer Advocacy Panel Face-to-Face Service Methods Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-05

... Face-to-Face Service Methods Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Face-to-Face Service Methods... Service Methods Project Committee will be held Tuesday, November 13, 2012, at 2:00 p.m. Eastern Time via...

77 FR 47166 - Open Meeting of the Taxpayer Advocacy Panel Face-to-Face Service Methods Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-07

... Face-to-Face Service Methods Project Committee AGENCY: Internal Revenue Service (IRS) Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Face-to-Face Service Methods... Service Methods Project Committee will be held Tuesday, September 11, 2012, at 2 p.m. Eastern Time via...

76 FR 78342 - Open Meeting of the Taxpayer Advocacy Panel Face-to-Face Service Methods Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

... Face-to-Face Service Methods Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of Meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Face-to-Face Service Methods... Service Methods Project Committee will be held Tuesday, January 10, 2012, at 2 p.m. Eastern Time via...

77 FR 2611 - Open Meeting of the Taxpayer Advocacy Panel Face-to-Face Service Methods Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-18

... Face-to-Face Service Methods Project Committee AGENCY: Internal Revenue Service (IRS) Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Face-to-Face Service Methods... Service Methods Project Committee will be held Tuesday, February 14, 2012, at 2 p.m. Eastern Time via...

42 CFR 59.205 - Project requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Project requirements. 59.205 Section 59.205 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS GRANTS FOR FAMILY PLANNING SERVICES Grants for Family Planning Service Training § 59.205 Project requirements. An approvable...

42 CFR 59.205 - Project requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Project requirements. 59.205 Section 59.205 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS GRANTS FOR FAMILY PLANNING SERVICES Grants for Family Planning Service Training § 59.205 Project requirements. An approvable...

42 CFR 59.205 - Project requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Project requirements. 59.205 Section 59.205 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS GRANTS FOR FAMILY PLANNING SERVICES Grants for Family Planning Service Training § 59.205 Project requirements. An approvable...

42 CFR 59.205 - Project requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Project requirements. 59.205 Section 59.205 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS GRANTS FOR FAMILY PLANNING SERVICES Grants for Family Planning Service Training § 59.205 Project requirements. An approvable...

Next-Generation Performance-Based Regulation. Volume 1: Introduction - Global Lessons for Success; Volume 2: Primer - Essential Elements of Design and Implementation; Volume 3: Innovative Examples from Around the World

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

Logan, Jeffrey S

Performance-based regulations (PBRs) provide a regulatory framework to connect goals, targets, and measures to utility performance or executive compensation. Well-designed PBRs provide incentives for utility performance, benefiting consumers and utility owners alike. This report considers the role of both PBRs and more discrete performance incentive mechanisms (PIMs) in 21st century power sector transformation. Innovative technologies are transforming the way electricity is generated, delivered, and consumed. PBRs have the potential to realign utility, investor, and consumer incentives and mitigate emerging challenges to the utility business model, renewable integration, and even cyber security.The goals of PBRs in the form of multi-year ratemore » plans are in many respects the same in terms of providing reasonably priced and reliable service to customers. However, today's technologies have changed, and there is more emphasis on clean energy. Thus, the pathways and the potential outcomes are different than they were in the 20th century when centralized generator stations and large infrastructure additions dominated the utility landscape. Given unprecedented changes underway in the electricity sector, PBRs - by specifying expectations of utility performance and outcomes for consumers, while staying agnostic to the exact means of delivery - constitute a form of prescient regulation that harnesses disruption. PBRs are one tool in a broader toolbox in the transition toward flexible regulatory and market structures that rewards utilities that adapt or evolve in reaction to market and technology change. PBRs and PIMs have great value for the electric industry when designed well and can be applied to many different situations. How exactly PBR mechanisms are most effectively enacted will vary based on the utility ownership model, institutional arrangements, and a variety of other local factors. PBRs should be tailored to the needs and goals of each jurisdiction, and perhaps each utility, to most effectively achieve the needs of a 21st century power grid in that jurisdiction. Presented in three volumes, this report highlights the lessons learned from their evolving history, explores essential elements of their design and implementation as well as considerations for how they may be best applied, and examines leading examples of PBRs from the United Kingdom, New York, Denmark, Mexico, and South Africa. The full report, 'Next-Generation Performance Based Regulation - Emphasizing Utility Performance to Unleash Power Sector Innovation,' published in September 2017, can be accessed at https://www.nrel.gov/docs/fy17osti/68512.pdf.« less

Polymorphism of alpha 1 antitrypsin in North American species of Canis

USGS Publications Warehouse

Federoff, N.E.; Kueppers, F.

2000-01-01

a1-Antitrypsin (A1AT) is a major protease inhibitor present in all mammalian sera that have thus far been investigated. A1AT is also highly polymorphic and is therefore a useful genetic marker. Previously reported A1AT polymorphism in domestic dogs consisted of two alleles designated as PiM and PiS which exhibited frequencies of 0.72 and 0.28, respectively, in a group of randomly collected mongrel dogs. North American species of Canis, which included gray wolves (n=29), Mexican wolves (n=20), coyotes (n=24), wolfdog crosses (n=9), and red wolves (n=27) were tested for A1AT polymorphism. A1AT phenotypes were determined by isoelectric focusing, followed by direct immunoblotting using a specific antiserum. A1AT concentrations were determined by radial immunodiffusion. Concentrations of A1AT were similar to those found in domestic dogs (2.26 + 0.3 mg/ml SD) and tended to be higher in females than in males, possibly indicating that A1AT may be hormonally influenced in females. Three phenotypic band patterns were observed (M, MS, S). The allele frequencies for domestic dogs and gray wolves were very similar, 0.72 and 0.69 for PiM and 0.28 and 0.31 for PiS, respectively. The Mexican wolves had a significantly lower frequency of PiS= 0.10. Coyotes and red wolves were all found to be monomorphic for the PiS allele and were indistinguishable from each other in that respect.

HF Propagation Effects Caused by an Artificial Plasma Cloud in the Ionosphere

NASA Astrophysics Data System (ADS)

Joshi, D. R.; Groves, K. M.; McNeil, W. J.; Caton, R. G.; Parris, R. T.; Pedersen, T. R.; Cannon, P. S.; Angling, M. J.; Jackson-Booth, N. K.

2014-12-01

In a campaign carried out by the NASA sounding rocket team, the Air Force Research Laboratory (AFRL) launched two sounding rockets in the Kwajalein Atoll, Marshall Islands, in May 2013 known as the Metal Oxide Space Cloud (MOSC) experiment to study the interactions of artificial ionization and the background plasma and measure the effects on high frequency (HF) radio wave propagation. The rockets released samarium metal vapor in the lower F-region of the ionosphere that ionized forming a plasma cloud that persisted for tens of minutes to hours in the post-sunset period. Data from the experiments has been analyzed to understand the impacts of the artificial ionization on HF radio wave propagation. Swept frequency HF links transiting the artificial ionization region were employed to produce oblique ionograms that clearly showed the effects of the samarium cloud. Ray tracing has been used to successfully model the effects of the ionized cloud. Comparisons between observations and modeled results will be presented, including model output using the International Reference Ionosphere (IRI), the Parameterized Ionospheric Model (PIM) and PIM constrained by electron density profiles measured with the ALTAIR radar at Kwajalein. Observations and modeling confirm that the cloud acted as a divergent lens refracting energy away from direct propagation paths and scattering energy at large angles relative to the initial propagation direction. The results confirm that even small amounts of ionized material injected in the upper atmosphere can result in significant changes to the natural propagation environment.

Electronegativity and intrinsic disorder of preeclampsia-related proteins.

PubMed

Polanco, Carlos; Castañón-González, Jorge Alberto; Uversky, Vladimir N; Buhse, Thomas; Samaniego Mendoza, José Lino; Calva, Juan J

2017-01-01

Preeclampsia, hemorrhage, and infection are the leading causes of maternal death in underdeveloped countries. Since several proteins associated with preeclampsia are known, we conducted a computational study which evaluated the commonness and potential functionality of intrinsic disorder of these proteins and also made an attempt to characterize their origin. The origin of the preeclampsia-related proteins was assessed with a supervised technique, a Polarity Index Method (PIM), which evaluates the electronegativity of proteins based solely on their sequence. The commonness of intrinsic disorder was evaluated using several disorder predictors from the PONDR family, the charge-hydropathy plot (CH-plot) and cumulative distribution function (CDF) analyses, and using the MobiDB web-based tool, whereas potential functionality of intrinsic disorder was studied with the D2P2 resource and ANCHOR predictor of disorder-based binding sites, and the STRING tool was used to build the interactivity networks of the preeclampsia-related proteins. Peculiarities of the PIM-derived polar profile of the group of preeclampsia-related proteins were then compared with profiles of a group of lipoproteins, antimicrobial peptides, angiogenesis-related proteins, and the intrinsically disordered proteins. Our results showed a high graphical correlation between preeclampsia proteins, lipoproteins, and the angiogenesis proteins. We also showed that many preeclampsia-related proteins contain numerous functional disordered regions. Therefore, these bioinformatics results led us to assume that the preeclampsia proteins are highly associated with the lipoproteins group, and that some preeclampsia-related proteins contain significant amounts of functional disorders.

Chromatographic Separation and Visual Detection on Wicking Microfluidic Devices: Quantitation of Cu2+ in Surface, Ground, and Drinking Water.

PubMed

Bandara, Gayan C; Heist, Christopher A; Remcho, Vincent T

2018-02-20

Copper is widely applied in industrial and technological applications and is an essential micronutrient for humans and animals. However, exposure to high environmental levels of copper, especially through drinking water, can lead to copper toxicity, resulting in severe acute and chronic health effects. Therefore, regular monitoring of aqueous copper ions has become necessary as recent anthropogenic activities have led to elevated environmental concentrations of copper. On-site monitoring processes require an inexpensive, simple, and portable analytical approach capable of generating reliable qualitative and quantitative data efficiently. Membrane-based lateral flow microfluidic devices are ideal candidates as they facilitate rapid, inexpensive, and portable measurements. Here we present a simple, chromatographic separation approach in combination with a visual detection method for Cu 2+ quantitation, performed in a lateral flow microfluidic channel. This method appreciably minimizes interferences by incorporating a nonspecific polymer inclusion membrane (PIM) based assay with a "dot-counting" approach to quantification. In this study, hydrophobic polycaprolactone (PCL)-filled glass microfiber (GMF) membranes were used as the base substrate onto which the PIM was evenly dispensed as an array of dots. The devices thus prepared were then selectively exposed to oxygen radicals through a mask to generate a hydrophilic surface path along which the sample was wicked. Using this approach, copper concentrations from 1 to 20 ppm were quantified from 5 μL samples using only visual observation of the assay device.

Automation of a high risk medication regime algorithm in a home health care population.

PubMed

Olson, Catherine H; Dierich, Mary; Westra, Bonnie L

2014-10-01

Create an automated algorithm for predicting elderly patients' medication-related risks for readmission and validate it by comparing results with a manual analysis of the same patient population. Outcome and Assessment Information Set (OASIS) and medication data were reused from a previous, manual study of 911 patients from 15 Medicare-certified home health care agencies. The medication data was converted into standardized drug codes using APIs managed by the National Library of Medicine (NLM), and then integrated in an automated algorithm that calculates patients' high risk medication regime scores (HRMRs). A comparison of the results between algorithm and manual process was conducted to determine how frequently the HRMR scores were derived which are predictive of readmission. HRMR scores are composed of polypharmacy (number of drugs), Potentially Inappropriate Medications (PIM) (drugs risky to the elderly), and Medication Regimen Complexity Index (MRCI) (complex dose forms, instructions or administration). The algorithm produced polypharmacy, PIM, and MRCI scores that matched with 99%, 87% and 99% of the scores, respectively, from the manual analysis. Imperfect match rates resulted from discrepancies in how drugs were classified and coded by the manual analysis vs. the automated algorithm. HRMR rules lack clarity, resulting in clinical judgments for manual coding that were difficult to replicate in the automated analysis. The high comparison rates for the three measures suggest that an automated clinical tool could use patients' medication records to predict their risks of avoidable readmissions. Copyright © 2014 Elsevier Inc. All rights reserved.

Pulmonary vascular clearance of harmful endogenous macromolecules in a porcine model of acute liver failure.

PubMed

Nedredal, Geir I; Elvevold, Kjetil; Chedid, Marcio F; Ytrebø, Lars M; Rose, Christopher F; Sen, Sambit; Smedsrød, Bård; Jalan, Rajiv; Revhaug, Arthur

2016-01-01

Pulmonary complications are common in acute liver failure (ALF). The role of the lungs in the uptake of harmful soluble endogenous macromolecules was evaluated in a porcine model of ALF induced by hepatic devascularization (n = 8) vs. controls (n = 8). In additional experiments, pulmonary uptake was investigated in healthy pigs. Fluorochrome-labeled modified albumin (MA) was applied to investigate the cellular uptake. As compared to controls, the ALF group displayed a 4-fold net increased lung uptake of hyaluronan, and 5-fold net increased uptake of both tissue plasminogen activator and lysosomal enzymes. Anatomical distribution experiments in healthy animals revealed that radiolabeled MA uptake (taken up by the same receptor as hyaluronan) was 53% by the liver, and 24% by the lungs. The lung uptake of LPS was 14% whereas 60% remained in the blood. Both fluorescence and electron microscopy revealed initial uptake of MA by pulmonary endothelial cells (PECs) with later translocation to pulmonary intravascular macrophages (PIMs). Moreover, the presence of PIMs was evident 10 min after injection. Systemic inflammatory markers such as leukopenia and increased serum TNF-α levels were evident after 20 min in the MA and LPS groups. Significant lung uptake of harmful soluble macromolecules compensated for the defect liver scavenger function in the ALF-group. Infusion of MA induced increased TNF-α serum levels and leukopenia, similar to the effect of the known inflammatory mediator LPS. These observations suggest a potential mechanism that may contribute to lung damage secondary to liver disease.

Practice-based learning can improve osteoporosis care.

PubMed

Hess, Brian J; Johnston, Mary M; Iobst, William F; Lipner, Rebecca S

2013-10-01

To examine physician engagement in practice-based learning using a self-evaluation module to assess and improve their care of individuals with or at risk of osteoporosis. Retrospective cohort study. Internal medicine and subspecialty clinics. Eight hundred fifty U.S. physicians with time-limited certification in general internal medicine or a subspecialty. Performance rates on 23 process measures and seven practice system domain scores were obtained from the American Board of Internal Medicine (ABIM) Osteoporosis Practice Improvement Module (PIM), an Internet-based self-assessment module that physicians use to improve performance on one targeted measure. Physicians remeasured performance on their targeted measures by conducting another medical chart review. Variability in performance on measures was found, with observed differences between general internists, geriatricians, and rheumatologists. Some practice system elements were modestly associated with measure performance; the largest association was between providing patient-centered self-care support and documentation of calcium intake and vitamin D estimation and counseling (correlation coefficients from 0.20 to 0.28, Ps < .002). For all practice types, the most commonly selected measure targeted for improvement was documentation of vitamin D level (38% of physicians). On average, physicians reported significant and large increases in performance on measures targeted for improvement. Gaps exist in the quality of osteoporosis care, and physicians can apply practice-based learning using the ABIM PIM to take action to improve the quality of care. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

49 CFR 633.11 - Covered projects.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF TRANSPORTATION PROJECT MANAGEMENT OVERSIGHT Project Management Oversight Services § 633.11 Covered projects. The Administrator may contract for project management oversight services when the... 49 Transportation 7 2010-10-01 2010-10-01 false Covered projects. 633.11 Section 633.11...

49 CFR 633.11 - Covered projects.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF TRANSPORTATION PROJECT MANAGEMENT OVERSIGHT Project Management Oversight Services § 633.11 Covered projects. The Administrator may contract for project management oversight services when the... 49 Transportation 7 2012-10-01 2012-10-01 false Covered projects. 633.11 Section 633.11...

49 CFR 633.11 - Covered projects.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF TRANSPORTATION PROJECT MANAGEMENT OVERSIGHT Project Management Oversight Services § 633.11 Covered projects. The Administrator may contract for project management oversight services when the... 49 Transportation 7 2013-10-01 2013-10-01 false Covered projects. 633.11 Section 633.11...

49 CFR 633.11 - Covered projects.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF TRANSPORTATION PROJECT MANAGEMENT OVERSIGHT Project Management Oversight Services § 633.11 Covered projects. The Administrator may contract for project management oversight services when the... 49 Transportation 7 2014-10-01 2014-10-01 false Covered projects. 633.11 Section 633.11...

49 CFR 633.11 - Covered projects.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF TRANSPORTATION PROJECT MANAGEMENT OVERSIGHT Project Management Oversight Services § 633.11 Covered projects. The Administrator may contract for project management oversight services when the... 49 Transportation 7 2011-10-01 2011-10-01 false Covered projects. 633.11 Section 633.11...

SAMS Acceleration Measurements on Mir From January to May 1997 (NASA Increment 4)

NASA Technical Reports Server (NTRS)

DeLombard, Richard

1998-01-01

During NASA Increment 4 (January to May 1997), about 5 gigabytes of acceleration data were collected by the Space Acceleration Measurements System (SAMS) onboard the Russian Space Station, Mir. The data were recorded on 28 optical disks which were returned to Earth on STS-84. During this increment, SAMS data were collected in the Priroda module to support the Mir Structural Dynamics Experiment (MiSDE), the Binary Colloidal Alloy Tests (BCAT), Angular Liquid Bridge (ALB), Candle Flames in Microgravity (CFM), Diffusion Controlled Apparatus Module (DCAM), Enhanced Dynamic Load Sensors (EDLS), Forced Flow Flame Spreading Test (FFFT), Liquid Metal Diffusion (LMD), Protein Crystal Growth in Dewar (PCG/Dewar), Queen's University Experiments in Liquid Diffusion (QUELD), and Technical Evaluation of MIM (TEM). This report points out some of the salient features of the microgravity environment to which these experiments were exposed. Also documented are mission events of interest such as the docked phase of STS-84 operations, a Progress engine burn, Soyuz vehicle docking and undocking, and Progress vehicle docking. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. The analyses included herein complement those presented in previous summary reports prepared by the Principal Investigator Microgravity Services (PIMS) group.

Service learning at dementia care programs: an orientation and training program.

PubMed

Lambert-Shute, Jennifer J; Jarrott, Shannon E; Fruhauf, Christine A

2004-01-01

The present paper describes a project that addresses the unique challenge service-learners face at dementia care programs. The project was conducted in conjunction with two courses on aging that offer students a service-learning (S-L) option at a university adult day service (ADS) program that accepts service-learners from these courses. The intervention consisted of two elements: (a) an orientation and follow- up sessions in which students learned about the causes of dementia, the behavioral characteristics exhibited by persons with dementia, and the best methods of interacting effectively with cognitively impaired persons; and (b) a structured scrapbook project for service-learners to exercise their new knowledge and skills. The authors designed the project to increase students' comfort in the dementia care setting and to facilitate students' knowledge of the elderly. The following sections describe the project and its procedures, benefits, and challenges. Recommendations for continuing the project and for adapting the project to other dementia sites are provided.

25 CFR 173.12 - Services from project.

Code of Federal Regulations, 2010 CFR

2010-04-01

... or any other type of service to the permittee, the cost of connecting the project facilities shall be... approved, at a rate to be approved by the Secretary which will reasonably reimburse the project for the... 25 Indians 1 2010-04-01 2010-04-01 false Services from project. 173.12 Section 173.12 Indians...

Alabama 622 Project Services to Deaf-Blind Children. Final Report.

ERIC Educational Resources Information Center

Graham, Terry; Bosarge, Zackie

This report describes activities and accomplishments of a 3-year federally supported project to improve services to children (ages 0-21) with deaf-blindness in Alabama. The project utilized a service delivery model based on provision of state, regional, local, and individual technical assistance to service providers and families through three…

42 CFR 59.208 - Use of project funds.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Use of project funds. 59.208 Section 59.208 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS GRANTS FOR FAMILY PLANNING SERVICES Grants for Family Planning Service Training § 59.208 Use of project funds. (a) Any funds granted...

42 CFR 59.208 - Use of project funds.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Use of project funds. 59.208 Section 59.208 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS GRANTS FOR FAMILY PLANNING SERVICES Grants for Family Planning Service Training § 59.208 Use of project funds. (a) Any funds granted...

42 CFR 59.208 - Use of project funds.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Use of project funds. 59.208 Section 59.208 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS GRANTS FOR FAMILY PLANNING SERVICES Grants for Family Planning Service Training § 59.208 Use of project funds. (a) Any funds granted...

42 CFR 59.208 - Use of project funds.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Use of project funds. 59.208 Section 59.208 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS GRANTS FOR FAMILY PLANNING SERVICES Grants for Family Planning Service Training § 59.208 Use of project funds. (a) Any funds granted...