Revisit on the thermodynamic stability of Hořava-Lifshitz black hole

NASA Astrophysics Data System (ADS)

Meng, Xudong; Wang, Ruihong

We study the thermodynamic properties of the black hole derived in Hořava-Lifshitz (HL) gravity without the detailed-balance condition. The parameter Ξ = 𝜖2 in the HL black hole plays the same role as that of the electric charge in the Reissner-Nordström-anti-de Sitter (RN-AdS) black hole. By analogy, we treat the parameter Ξ as the thermodynamic variable and obtain the first law of thermodynamics for the HL black hole. Although the HL black hole and the RN-AdS black hole have the similar mass and temperature, due to their very different entropy, the two black holes have very different thermodynamic properties. By calculating the heat capacity and the free energy, we analyze the thermodynamic stability of the HL black hole.

Taraxinic acid, a hydrolysate of sesquiterpene lactone glycoside from the Taraxacum coreanum NAKAI, induces the differentiation of human acute promyelocytic leukemia HL-60 cells.

PubMed

Choi, Jung-Hye; Shin, Kyung-Min; Kim, Na-Young; Hong, Jung-Pyo; Lee, Yong Sup; Kim, Hyoung Ja; Park, Hee-Juhn; Lee, Kyung-Tae

2002-11-01

The present work was performed to elucidate the active moiety of a sesquiterpene lactone, taraxinic acid-1'-O-beta-D-glucopyranoside (1). from Taraxacum coreanum NAKAI on the cytotoxicity of various cancer cells. Based on enzymatic hydrolysis and MTT assay, the active moiety should be attributed to the aglycone taraxinic acid (1a). rather than the glycoside (1). Taraxinic acid exhibited potent antiproliferative activity against human leukemia-derived HL-60. In addition, this compound was found to be a potent inducer of HL-60 cell differentiation as assessed by a nitroblue tetrazolium reduction test, esterase activity assay, phagocytic activity assay, morphology change, and expression of CD 14 and CD 66 b surface antigens. These results suggest that taraxinic acid induces the differentiation of human leukemia cells to monocyte/macrophage lineage. Moreover, the expression level of c-myc was down-regulated during taraxinic acid-dependent HL-60 cell differentiation, whereas p21(CIP1) and p27(KIP1) were up-regulated. Taken together, our results suggest that taraxinic acid may have potential as a therapeutic agent in human leukemia.

Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion.

PubMed

Boedeker, J C; Doolittle, M H; White, A L

2001-11-01

Combined lipase deficiency (cld) is a recessively inherited disorder in mice associated with a deficiency of LPL and hepatic lipase (HL) activity. LPL is synthesized in cld tissues but is retained in the endoplasmic reticulum (ER), whereas mouse HL (mHL) is secreted but inactive. In this study we investigated the effect of cld on the secretion of human HL (hHL) protein mass and activity. Differentiated liver cell lines were derived from cld mice and their normal heterozygous (het) littermates by transformation of hepatocytes with SV40 large T antigen. After transient transfection with lipase expression constructs, secretion of hLPL activity from cld cells was only 12% of that from het cells. In contrast, the rate of secretion of hHL activity and protein mass per unit of expressed hHL mRNA was identical for the two cell lines. An intermediate effect was observed for mHL, with a 46% reduction in secretion of activity from cld cells. The ER glucosidase inhibitor, castanospermine, decreased secretion of both hLPL and hHL from het cells by approximately 70%, but by only approximately 45% from cld cells. This is consistent with data suggesting that cld may result from a reduced concentration of the ER chaperone calnexin. In conclusion, our results demonstrate a differential effect of cld on hLPL, mHL, and hHL secretion, suggesting differential requirements for activation and exit of the enzymes from the ER.

Metabolite profiling and transcript analysis reveal specificities in the response of a berry derived cell culture to abiotic stresses

PubMed Central

Ayenew, Biruk; Degu, Asfaw; Manela, Neta; Perl, Avichai; Shamir, Michal O.; Fait, Aaron

2015-01-01

As climate changes, there is a need to understand the expected effects on viticulture. In nature, stresses exist in a combined manner, hampering the elucidation of the effect of individual cues on grape berry metabolism. Cell suspension culture originated from pea-size Gamy Red grape berry was used to harness metabolic response to high light (HL; 2500 μmol m-2s-1), high temperature (HT; 40°C) and their combination in comparison to 25°C and 100 μmol m-2s-1 under controlled condition. When LC–MS and GC–MS based metabolite profiling was implemented and integrated with targeted RT-qPCR transcript analysis specific responses were observed to the different cues. HL enhanced polyphenol metabolism while HT and its combination with HL induced amino acid and organic acid metabolism with additional effect on polyphenols. The trend of increment in TCA cycle genes like ATCs, ACo1, and IDH in the combined treatment might support the observed increment in organic acids, GABA shunt, and their derivatives. The apparent phenylalanine reduction with polyphenol increment under HL suggests enhanced fueling of the precursor toward the downstream phenylpropanoid pathway. In the polyphenol metabolism, a differential pattern of expression of flavonoid 3′,5′ hydroxylase and flavonoid 3′ hydroxylase was observed under high light (HL) and combined cues which were accompanied by characteristic metabolite profiles. HT decreased glycosylated cyanidin and peonidin forms while the combined cues increased acetylated and coumarylated peonidin forms. Transcription factors regulating anthocyanin metabolism and their methylation, MYB, OMT, UFGT, and DFR, were expressed differentially among the treatments, overall in agreement with the metabolite profiles. Taken together these data provide insights into the coordination of central and secondary metabolism in relation to multiple abiotic stresses. PMID:26442042

"It's Very Complicated" Exploring Heritage Language Identity with Heritage Language Teachers in a Teacher Preparation Program

ERIC Educational Resources Information Center

Cho, Hyesun

2014-01-01

Despite the proliferation of research in heritage language (HL) education, pedagogically based research that examines teacher education practice for promoting critical reflection of HL teachers is sparse. This article describes how preservice teachers working in community-based HL schools changed their views of HL identity during their…

Working with the HL7 metamodel in a Model Driven Engineering context.

PubMed

Martínez-García, A; García-García, J A; Escalona, M J; Parra-Calderón, C L

2015-10-01

HL7 (Health Level 7) International is an organization that defines health information standards. Most HL7 domain information models have been designed according to a proprietary graphic language whose domain models are based on the HL7 metamodel. Many researchers have considered using HL7 in the MDE (Model-Driven Engineering) context. A limitation has been identified: all MDE tools support UML (Unified Modeling Language), which is a standard model language, but most do not support the HL7 proprietary model language. We want to support software engineers without HL7 experience, thus real-world problems would be modeled by them by defining system requirements in UML that are compliant with HL7 domain models transparently. The objective of the present research is to connect HL7 with software analysis using a generic model-based approach. This paper introduces a first approach to an HL7 MDE solution that considers the MIF (Model Interchange Format) metamodel proposed by HL7 by making use of a plug-in developed in the EA (Enterprise Architect) tool. Copyright © 2015 Elsevier Inc. All rights reserved.

Results of a feasibility study using the Newton-Raphson digital computer program to identify lifting body derivatives from flight data

NASA Technical Reports Server (NTRS)

Sim, A. G.

1973-01-01

A brief study was made to assess the applicability of the Newton-Raphson digital computer program as a routine technique for extracting aerodynamic derivatives from flight tests of lifting body types of vehicles. Lateral-direction flight data from flight tests of the HL-10 lifting body reserch vehicle were utilized. The results in general, show the computer program to be a reliable and expedient means for extracting derivatives for this class of vehicles as a standard procedure. This result was true even when stability augmentation was used. As a result of the study, a credible set of HL-10 lateral-directional derivatives was obtained from flight data. These derivatives are compared with results from wind-tunnel tests.

Applications of several spectral techniques to characterize coordination compounds derived from 2,6-diacetylpyridine derivative

NASA Astrophysics Data System (ADS)

Chandra, Sulekh; Sharma, Amit Kumar

2009-09-01

The coordination compounds of Cr III, Mn II and Co II metal ions derived from quinquedentate 2,6-diacetylpyridine derivative have been synthesized and characterized by using the various physicochemical studies like stoichiometric, molar conductivity and magnetic, and spectral techniques like IR, NMR, mass, UV and EPR. The general stoichiometries of the complexes are found to be [Cr(H 2L)X] and [M(HL)X], where M = Mn(II) and Co(II); H 2L = dideprotonated ligand, HL = monodeprotonated ligand and X = NO 3-, Cl - and OAc -. The studies reveal that the complexes possess monomeric compositions with six coordinated octahedral geometry (Cr III and Mn II complexes) and six coordinated tetragonal geometry (Co II complexes).

HMG CoA Lyase (HL): Mutation detection and development of a bacterial expression system for screening the activity of mutant alleles from HL-deficient patients

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

Robert, M.F.; Ashmarina, L.; Poitier, E.

1994-09-01

HL catalyzes the last step of ketogenesis, and autosomal recessive HL deficiency in humans can cause episodes of hypoglycemia and coma. Structurally, HL is a dimer of identical 325-residue peptides which requires a reducing environment to maintain activity. We cloned the human and mouse HL cDNAs and genes and have performed mutation analysis on cells from 30 HL-deficient probands. Using SSCP and also genomic Southern analysis we have identified putative mutations on 53/60 alleles of these patients (88%). To date, we have found 20 mutations: 3 large deletions, 4 termination mutations, 5 frameshift mutations, and 8 missense mutations which wemore » suspect to be pathogenic based on evolutionary conservation and/or our previous studies on purified HL protein. We have also identified 3 polymorphic variants. In order to directly test the activity of the missense mutations, we established a pGEX-based system, using a glutathione S transferase (GST)-HL fusion protein. Expressed wild-type GST-HL was insoluble. We previously located a reactive Cys at the C-terminus of chicken HL which is conserved in human HL. We produced a mutant HL peptide, C323S, which replaced Cys323 with Ser. Purified C323S is soluble and has similar kinetics to wild-type HL. C323S-containing GST-HL is soluble and enzymatically active. We are cloning and expressing the 8 missense mutations.« less

Towards Positional Isolation of Three Quantitative Trait Loci Conferring Resistance to Powdery Mildew in Two Spanish Barley Landraces

PubMed Central

Silvar, Cristina; Perovic, Dragan; Nussbaumer, Thomas; Spannagl, Manuel; Usadel, Björn; Casas, Ana; Igartua, Ernesto; Ordon, Frank

2013-01-01

Three quantitative trait loci (QTL) conferring broad spectrum resistance to powdery mildew, caused by the fungus Blumeria graminis f. sp. hordei, were previously identified on chromosomes 7HS, 7HL and 6HL in the Spanish barley landrace-derived lines SBCC097 and SBCC145. In the present work, a genome-wide putative linear gene index of barley (Genome Zipper) and the first draft of the physical, genetic and functional sequence of the barley genome were used to go one step further in the shortening and explicit demarcation on the barley genome of these regions conferring resistance to powdery mildew as well as in the identification of candidate genes. First, a comparative analysis of the target regions to the barley Genome Zippers of chromosomes 7H and 6H allowed the development of 25 new gene-based molecular markers, which slightly better delimit the QTL intervals. These new markers provided the framework for anchoring of genetic and physical maps, figuring out the outline of the barley genome at the target regions in SBCC097 and SBCC145. The outermost flanking markers of QTLs on 7HS, 7HL and 6HL defined a physical area of 4 Mb, 3.7 Mb and 3.2 Mb, respectively. In total, 21, 10 and 16 genes on 7HS, 7HL and 6HL, respectively, could be interpreted as potential candidates to explain the resistance to powdery mildew, as they encode proteins of related functions with respect to the known pathogen defense-related processes. The majority of these were annotated as belonging to the NBS-LRR class or protein kinase family. PMID:23826271

Total synthesis of natural derivatives and artificial analogs of 13-oxyingenol and their biological evaluation.

PubMed

Ohyoshi, Takayuki; Tamura, Yuki; Hayakawa, Ichiro; Hirai, Go; Miyazawa, Yamato; Funakubo, Shota; Sodeoka, Mikiko; Kigoshi, Hideo

2016-12-28

We have established an efficient synthetic methodology for the 13-oxyingenol natural derivative (13-oxyingenol-13-dodecanoate-20-hexanoate), featuring a ring-closing olefin metathesis reaction for the "direct" construction of a highly strained inside-outside framework and a Mislow-Evans-type [2,3]-sigmatropic rearrangement for the stereoselective introduction of the hydroxy group at C5. We also synthesized artificial analogs of 13-oxyingenol and ingenol by using our synthetic strategy. In vitro activation assays of protein kinase C (PKC) α and δ revealed that the dodecanoyl group at O13 on 13-oxyingenol analogs had a significant role in PKCδ activation. The PKCα- or PKCδ-activating 13-oxyingenol and ingenol analogs induced both distinct morphological changes and increases of CD11b expression in HL-60 cells, which would be typical signs of HL-60 cell differentiation to macrophage-like cells, as expected by previous reports. Intriguingly, however, similar differentiation phenotypes were observed with the use of 13-oxyingenol natural derivatives and 13-oxyingenol-13-dodecanoate showing a remarkably less potent PKCα or PKCδ activation ability, which the PKC inhibitor Gö6983 diminished. This indicated the involvement of other PKC isozymes or related kinase activities. 13-Oxyingenol analogs, which induced HL-60 cell differentiation, also induced HL-60 cell death, similar to the action of a phorbol ester, a strong PKC activator.

[HL7 standard--features, principles, and methodology].

PubMed

Koncar, Miroslav

2005-01-01

The mission of HL7 Inc. non-profit organization is to provide standards for the exchange, management and integration of data that support clinical patient care, and the management, delivery and evaluation of healthcare services. As the standards developed by HL7 Inc. represent the world's most influential standardization efforts in the field of medical informatics, the HL7 family of standards has been recognized by the technical and scientific community as the foundation for the next generation healthcare information systems. Versions 1 and 2 of HL7 standard have solved many issues, but also demonstrated the size and complexity of health information sharing problem. As the solution complete new methodology has been adopted that is encompassed in the HL7 Version 3 recommendations. This approach standardizes Reference Information Model (RIM), which is the source of all derived domain models and message structures. Message design is now defined in detail, enabling interoperability between loosely coupled systems that are.designed by different vendors and deployed in various environments. At the start of the Primary Healthcare Information System project in the Republic of Croatia in 2002, the decision was to go directly to Version 3. The target scope of work includes clinical, financial and administrative data management in the domain of healthcare processes. By using HL7v3 standardized methodology we were able to completely map the Croatian primary healthcare domain to HL7v3 artefacts. Further refinement processes that are planned for the future will provide semantic interoperability and detailed description of all elements in HL7 messages. Our HL7 Business Component is in constant process of studying different legacy applications, making solid foundation for their integration to HL7-enabled communication environment.

The Influence of Parental Health Literacy Status on Reach, Attendance, Retention, and Outcomes in a Family-Based Childhood Obesity Treatment Program, Virginia, 2013-2015.

PubMed

Zoellner, Jamie M; Hill, Jennie; You, Wen; Brock, Donna; Frisard, Madlyn; Alexander, Ramine; Silva, Fabiana; Price, Bryan; Marshall, Ruby; Estabrooks, Paul A

2017-09-28

Few interventions have evaluated the influence of parent health literacy (HL) status on weight-related child outcomes. This study explores how parent HL affects the reach, attendance, and retention of and outcomes in a 3-month multicomponent family-based program to treat childhood obesity (iChoose). This pre-post, quasiexperimental trial occurred in the Dan River Region, a federally designated medically underserved area. iChoose research protocol and intervention strategies were designed using an HL universal precautions approach. We used validated measures, standardized data collection techniques, and generalized linear mixed-effect parametric models to determine the moderation effect of parent HL on outcomes. No significant difference in HL scores were found between parents who enrolled their child in the study and those who did not. Of 94 enrolled parents, 34% were low HL, 49% had an annual household income of less than $25,000, and 39% had a high school education or less. Of 101 enrolled children, 60% were black, and the mean age was 9.8 (standard deviation, 1.3) years. Children of parents with both low and high HL attended and were retained at similar rates. Likewise, parent HL status did not significantly influence improvements in effectiveness outcomes (eg, child body mass index [BMI] z scores, parent BMI, diet and physical activity behaviors, quality of life), with the exception of child video game/computer screen time; low HL decreased and high HL increased screen time (coefficient = 0.52, standard error, 0.11, P < .001). By incorporating design features that attended to the HL needs of parents, children of parents with low HL engaged in and benefited from a family-based childhood obesity treatment program similar to children of parents with high HL.

Simplifying HL7 Version 3 messages.

PubMed

Worden, Robert; Scott, Philip

2011-01-01

HL7 Version 3 offers a semantically robust method for healthcare interoperability but has been criticized as overly complex to implement. This paper reviews initiatives to simplify HL7 Version 3 messaging and presents a novel approach based on semantic mapping. Based on user-defined definitions, precise transforms between simple and full messages are automatically generated. Systems can be interfaced with the simple messages and achieve interoperability with full Version 3 messages through the transforms. This reduces the costs of HL7 interfacing and will encourage better uptake of HL7 Version 3 and CDA.

Novel thiourea derivative and its complexes: Synthesis, characterization, DFT computations, thermal and electrochemical behavior, antioxidant and antitumor activities

NASA Astrophysics Data System (ADS)

Yeşilkaynak, Tuncay; Muslu, Harun; Özpınar, Celal; Emen, Fatih Mehmet; Demirdöğen, Ruken Esra; Külcü, Nevzat

2017-08-01

A novel thiourea derivative, N-((2-chloropyridin-3-yl)carbamothioyl) thiophene-2-carboxamide,C11H8ClN3OS2 (HL) and its Co(II), Ni(II) and Cu(II) complexes (ML2 type) were prepared and characterized by elemental analysis, FT-IR,1H NMR and HR-MS methods. The crystal structure of HL was also investigated by single crystal X-ray diffraction study. The HL crystallizes in the orthorhombic crystal system with P 21 21 21 space group, Z = 4, a = 3.8875(3) Å, b = 14.6442(13) Å, c = 21.8950(19) Å. The [ML2] complex structures were optimized by using B97D/TZVP level. Molecular orbitals of HL ligand were calculated at the same level. Thermal and electrochemical behaviors of the complexes were investigated. Anticancer and antioxidant activities of the complexes were also investigated. Antioxidant activities were determined by using DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2‧-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) assays. Anticancer activities were studied via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in MCF-7 (Michigan Cancer Foundation-7) breast cancer cells.

Population-based study of Hodgkin's lymphoma in Kuwait.

PubMed

Alshemmari, S; Sajnani, K P; Refaat, S; Albassami, A

2011-01-01

Hodgkin lymphoma (HL) comprises about 25% of all malignant nodal lymphomas worldwide. Incidence of HL has been increasing in many countries around the world, in the western countries in particular. Cancer incidence variations in different ethnic groups in the same country can lead to some important information about the search of etiological factors. Some researchers found an association between ethnicity and increased risk of HL. In this study, we evaluated the epidemiologic and clinical characteristics of patients with HL and the HL subtypes in Kuwait who were diagnosed between 1998 and 2006 and we analyzed the changes in the incidence of HL over time based on age, sex, and ethnicity. The Kuwait Cancer Control Center is a tertiary referral hospital and the only cancer hospital in the entire state of Kuwait. We identified 293 patients who were newly diagnosed with HL by histopathology between January 1, 1998, and December 31, 2006, at the Kuwait Cancer Control Center. Incidence data were crossvalidated with the population-based Cancer Registry of Kuwait. Clinical data were obtained by reviewing the patients' medical records. The median age at diagnosis was 39 years (range, 10-85 years) for patients with cHL and 36 years (range, 14-51 years) for patients with NLPHL. The age-adjusted incidence rate was 2.1 cases (range, 1.2-2.9) per 100,000 people per year in the period between 1998 and 2006. NLPHL and cHL were predominant in men with a male to female ratio of 2:1. However, the mean annual percentage change in HL incidence among Kuwaiti patients and non-Kuwaiti patients per year showed unexplained higher percentage in females both Kuwaiti and non-Kuwaiti. cHL comprised 92.5% of all HL cases and NLPHL comprised 7.5%. Nodular sclerosis was the predominant histologic subtype of cHL (58.9%), whereas mixed cellularity was the second most frequent histologic subtype of cHL, (25.9%). Although the incidence of HL was slightly lower in Kuwait than the worldwide incidence; it was similar to Asian descent population. Incidence of HL varied in the same country among different ethnic subgroups. The mean annual percentage change increased in Kuwaiti and non-Kuwaiti females.

Relationship between structure and antiproliferative activity of polymethoxyflavones towards HL60 cells.

PubMed

Kawaii, Satoru; Ikuina, Tomoyasu; Hikima, Takeshi; Tokiwano, Tetsuo; Yoshizawa, Yuko

2012-12-01

As part of our continuing investigation of polymethoxyflavone (PMF) derivatives as potential anticancer substances, a series of PMF derivatives was synthesized. The synthesized compounds were evaluated for cytotoxicity against the promyelocytic leukemic HL60 cell line, and structure-activity relationship correlations were investigated along with previously isolated PMFs from the peel of king orange (Citrus nobilis). 7,3'-Dimethoxyflavone demonstrated the most potent activity among the synthetic PMFs. Consideration of correlation between the methoxylation pattern and antiproliferative activity revealed the importance of the 3'-methoxyl group and the higher degree of methoxylation on the A-ring moiety of PMFs.

The Ling 6(HL) test: typical pediatric performance data and clinical use evaluation.

PubMed

Glista, Danielle; Scollie, Susan; Moodie, Sheila; Easwar, Vijayalakshmi

2014-01-01

The Ling 6(HL) test offers a calibrated version of naturally produced speech sounds in dB HL for evaluation of detection thresholds. Aided performance has been previously characterized in adults. The purpose of this work was to evaluate and refine the Ling 6(HL) test for use in pediatric hearing aid outcome measurement. This work is presented across two studies incorporating an integrated knowledge translation approach in the characterization of normative and typical performance, and in the evaluation of clinical feasibility, utility, acceptability, and implementation. A total of 57 children, 28 normally hearing and 29 with binaural sensorineural hearing loss, were included in Study 1. Children wore their own hearing aids fitted using Desired Sensation Level v5.0. Nine clinicians from The Network of Pediatric Audiologists participated in Study 2. A CD-based test format was used in the collection of unaided and aided detection thresholds in laboratory and clinical settings; thresholds were measured clinically as part of routine clinical care. Confidence intervals were derived to characterize normal performance and typical aided performance according to hearing loss severity. Unaided-aided performance was analyzed using a repeated-measures analysis of variance. The audiologists completed an online questionnaire evaluating the quality, feasibility/executability, utility/comparative value/relative advantage, acceptability/applicability, and interpretability, in addition to recommendation and general comments sections. Ling 6(HL) thresholds were reliably measured with children 3-18 yr old. Normative and typical performance ranges were translated into a scoring tool for use in pediatric outcome measurement. In general, questionnaire respondents generally agreed that the Ling 6(HL) test was a high-quality outcome evaluation tool that can be implemented successfully in clinical settings. By actively collaborating with pediatric audiologists and using an integrated knowledge translation framework, this work supported the creation of an evidence-based clinical tool that has the potential to be implemented in, and useful to, clinical practice. More research is needed to characterize performance in alternative listening conditions to facilitate use with infants, for example. Future efforts focused on monitoring the use of the Ling 6(HL) test in daily clinical practice may help describe whether clinical use has been maintained across time and if any additional adaptations are necessary to facilitate clinical uptake. American Academy of Audiology.

Flight-determined derivatives and dynamic characteristics for the HL-10 lifting body vehicle at subsonic and transonic Mach numbers

NASA Technical Reports Server (NTRS)

Strutz, L. W.

1972-01-01

The HL-10 lifting body stability and control derivatives were determined by using an analog-matching technique and compared with derivatives obtained from wind-tunnel results. The flight derivatives were determined as a function of angle of attack for a subsonic configuration at Mach 0.7 and for a transonic configuration at Mach 0.7, 0.9, and 1.2. At an angle of attack of 14 deg, data were obtained for a Mach number range from 0.6 to 1.4. The flight and wind-tunnel derivatives were in general agreement, with the possible exception of the longitudinal and lateral damping derivatives. Some differences were noted between the vehicle dynamic response characteristics calculated from flight-determined derivatives and those predicted by the wind-tunnel results. However, the only difference the pilots noted between the response of the vehicle in flight and the response of a simulator programed with wind-tunnel-predicted data was that the damping generally was higher in the flight vehicle.

Libraries of 2β-(N-substituted piperazino)-5α-androstane-3α, 17β-diols: chemical synthesis and cytotoxic effects on human leukemia HL-60 cells and on normal lymphocytes.

PubMed

Roy, Jenny; Maltais, René; Jegham, Hajer; Poirier, Donald

2011-05-01

Libraries of steroid derivatives with two levels of molecular diversity were prepared to optimize the antiproliferative activity on leukemia HL-60 cells by first varying the amino acid (AA) at R(1) (libraries A, B, C, and D: with 45, 45, 20, and 20 members, respectively) and, subsequently, the capping group at R(2) (library E: 168 members). The screening of these aminosteroids revealed interesting structure-activity relationships. In library A, the compounds bearing a tetrahydroisoquinolone residue as the first element of diversity showed potent cytotoxicity, principally when isovaleric or cyclohexyl acetic acid was used as a capping group (>40% of cell growth inhibition at 1 μM). In library B, the phenylalanine (Phe) derivatives bearing a cyano group induced a higher growth inhibition than the other Phe derivatives. The screening of library C indicated the increase of hydrophobicity of proline (Pro) seems to preserve the cytotoxic effect achieved by the lead compound. However, the synthesis of structural Pro variants (library D) clearly shows weaker activities when compared to L-Pro building blocks. Finally, by incorporating some of the most active AA of libraries A-D in library E, we observed that the amide coupling functionality gave stronger cytotoxic activity compared to the corresponding sulfonamides or benzylamines. Six of the most active amide derivatives (E-37P, E-41P, E-42P, E-46P, E-48F, and E-12T) were selected and IC(50) determined on HL-60 cells as well as on normal human lymphocytes. Among this series of new anticancer agents, good to high selectivity indices (SI = IC(50) (lymphocytes)/IC(50) (HL-60 cells) = 5 - 55) were obtained.

Hollow latex particles functionalized with chitosan for the removal of formaldehyde from indoor air.

PubMed

Nuasaen, Sukanya; Opaprakasit, Pakorn; Tangboriboonrat, Pramuan

2014-01-30

Chitosan and polyethyleneimine (PEI) functionalized hollow latex (HL) particles were conveniently fabricated by coating poly(methyl methacrylate-co-divinyl benzene-co-acrylic acid) (P(MMA/DVB/AA)) HL particles with 5 wt% chitosan or 14 wt% PEI. The materials were used as formaldehyde adsorbent, where their adsorbent activity was examined by Fourier Transform Infrared (FTIR) spectroscopy. The nucleophilic addition of amines to carbonyls generated a carbinolamine intermediate with a characteristic band at 1,020 cm(-1) and Schiff base product at 1650 cm(-1), whose intensity increased with prolonged formaldehyde exposure times. The major products observed in HL-chitosan were carbinolamine and Schiff base, whereas a small amount of Schiff base was obtained in HL-PEI particles, confirming a chemical bond formation without re-emission of formaldehyde. Compared to HL-PEI, HL-chitosan possesses higher formaldehyde adsorption efficiency. Besides providing opacity and whiteness, the multilayer HL-chitosan particles can effectively remove indoor air pollutants, i.e., formaldehyde gas, and, hence, would be useful in special coating applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mutations That Alter the Bacterial Cell Envelope Increase Lipid Production

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

Lemmer, Kimberly C.; Zhang, Weiping; Langer, Samantha J.

ABSTRACT Lipids from microbes offer a promising source of renewable alternatives to petroleum-derived compounds. In particular, oleaginous microbes are of interest because they accumulate a large fraction of their biomass as lipids. In this study, we analyzed genetic changes that alter lipid accumulation inRhodobacter sphaeroides. By screening anR. sphaeroidesTn5mutant library for insertions that increased fatty acid content, we identified 10 high-lipid (HL) mutants for further characterization. These HL mutants exhibited increased sensitivity to drugs that target the bacterial cell envelope and changes in shape, and some had the ability to secrete lipids, with two HL mutants accumulating ~60% of their totalmore » lipids extracellularly. When one of the highest-lipid-secreting strains was grown in a fed-batch bioreactor, its lipid content was comparable to that of oleaginous microbes, with the majority of the lipids secreted into the medium. Based on the properties of these HL mutants, we conclude that alterations of the cell envelope are a previously unreported approach to increase microbial lipid production. We also propose that this approach may be combined with knowledge about biosynthetic pathways, in this or other microbes, to increase production of lipids and other chemicals. IMPORTANCEThis paper reports on experiments to understand how to increase microbial lipid production. Microbial lipids are often cited as one renewable replacement for petroleum-based fuels and chemicals, but strategies to increase the yield of these compounds are needed to achieve this goal. While lipid biosynthesis is often well understood, increasing yields of these compounds to industrially relevant levels is a challenge, especially since genetic, synthetic biology, or engineering approaches are not feasible in many microbes. We show that altering the bacterial cell envelope can be used to increase microbial lipid production. We also find that the utility of some of these alterations can be enhanced by growing cells in bioreactor configurations that can be used industrially. We propose that our findings can inform current and future efforts to increase production of microbial lipids, other fuels, or chemicals that are currently derived from petroleum.« less

Mutations That Alter the Bacterial Cell Envelope Increase Lipid Production

DOE PAGES

Lemmer, Kimberly C.; Zhang, Weiping; Langer, Samantha J.; ...

2017-05-23

ABSTRACT Lipids from microbes offer a promising source of renewable alternatives to petroleum-derived compounds. In particular, oleaginous microbes are of interest because they accumulate a large fraction of their biomass as lipids. In this study, we analyzed genetic changes that alter lipid accumulation inRhodobacter sphaeroides. By screening anR. sphaeroidesTn5mutant library for insertions that increased fatty acid content, we identified 10 high-lipid (HL) mutants for further characterization. These HL mutants exhibited increased sensitivity to drugs that target the bacterial cell envelope and changes in shape, and some had the ability to secrete lipids, with two HL mutants accumulating ~60% of their totalmore » lipids extracellularly. When one of the highest-lipid-secreting strains was grown in a fed-batch bioreactor, its lipid content was comparable to that of oleaginous microbes, with the majority of the lipids secreted into the medium. Based on the properties of these HL mutants, we conclude that alterations of the cell envelope are a previously unreported approach to increase microbial lipid production. We also propose that this approach may be combined with knowledge about biosynthetic pathways, in this or other microbes, to increase production of lipids and other chemicals. IMPORTANCEThis paper reports on experiments to understand how to increase microbial lipid production. Microbial lipids are often cited as one renewable replacement for petroleum-based fuels and chemicals, but strategies to increase the yield of these compounds are needed to achieve this goal. While lipid biosynthesis is often well understood, increasing yields of these compounds to industrially relevant levels is a challenge, especially since genetic, synthetic biology, or engineering approaches are not feasible in many microbes. We show that altering the bacterial cell envelope can be used to increase microbial lipid production. We also find that the utility of some of these alterations can be enhanced by growing cells in bioreactor configurations that can be used industrially. We propose that our findings can inform current and future efforts to increase production of microbial lipids, other fuels, or chemicals that are currently derived from petroleum.« less

Mutations That Alter the Bacterial Cell Envelope Increase Lipid Production.

PubMed

Lemmer, Kimberly C; Zhang, Weiping; Langer, Samantha J; Dohnalkova, Alice C; Hu, Dehong; Lemke, Rachelle A; Piotrowski, Jeff S; Orr, Galya; Noguera, Daniel R; Donohue, Timothy J

2017-05-23

Lipids from microbes offer a promising source of renewable alternatives to petroleum-derived compounds. In particular, oleaginous microbes are of interest because they accumulate a large fraction of their biomass as lipids. In this study, we analyzed genetic changes that alter lipid accumulation in Rhodobacter sphaeroides By screening an R. sphaeroides Tn 5 mutant library for insertions that increased fatty acid content, we identified 10 high-lipid (HL) mutants for further characterization. These HL mutants exhibited increased sensitivity to drugs that target the bacterial cell envelope and changes in shape, and some had the ability to secrete lipids, with two HL mutants accumulating ~60% of their total lipids extracellularly. When one of the highest-lipid-secreting strains was grown in a fed-batch bioreactor, its lipid content was comparable to that of oleaginous microbes, with the majority of the lipids secreted into the medium. Based on the properties of these HL mutants, we conclude that alterations of the cell envelope are a previously unreported approach to increase microbial lipid production. We also propose that this approach may be combined with knowledge about biosynthetic pathways, in this or other microbes, to increase production of lipids and other chemicals. IMPORTANCE This paper reports on experiments to understand how to increase microbial lipid production. Microbial lipids are often cited as one renewable replacement for petroleum-based fuels and chemicals, but strategies to increase the yield of these compounds are needed to achieve this goal. While lipid biosynthesis is often well understood, increasing yields of these compounds to industrially relevant levels is a challenge, especially since genetic, synthetic biology, or engineering approaches are not feasible in many microbes. We show that altering the bacterial cell envelope can be used to increase microbial lipid production. We also find that the utility of some of these alterations can be enhanced by growing cells in bioreactor configurations that can be used industrially. We propose that our findings can inform current and future efforts to increase production of microbial lipids, other fuels, or chemicals that are currently derived from petroleum. Copyright © 2017 Lemmer et al.

Phenotypic responses to interspecies competition and commensalism in a naturally-derived microbial co-culture.

PubMed

Khan, Nymul; Maezato, Yukari; McClure, Ryan S; Brislawn, Colin J; Mobberley, Jennifer M; Isern, Nancy; Chrisler, William B; Markillie, Lye Meng; Barney, Brett M; Song, Hyun-Seob; Nelson, William C; Bernstein, Hans C

2018-01-10

The fundamental question of whether different microbial species will co-exist or compete in a given environment depends on context, composition and environmental constraints. Model microbial systems can yield some general principles related to this question. In this study we employed a naturally occurring co-culture composed of heterotrophic bacteria, Halomonas sp. HL-48 and Marinobacter sp. HL-58, to ask two fundamental scientific questions: 1) how do the phenotypes of two naturally co-existing species respond to partnership as compared to axenic growth? and 2) how do growth and molecular phenotypes of these species change with respect to competitive and commensal interactions? We hypothesized - and confirmed - that co-cultivation under glucose as the sole carbon source would result in competitive interactions. Similarly, when glucose was swapped with xylose, the interactions became commensal because Marinobacter HL-58 was supported by metabolites derived from Halomonas HL-48. Each species responded to partnership by changing both its growth and molecular phenotype as assayed via batch growth kinetics and global transcriptomics. These phenotypic responses depended on nutrient availability and so the environment ultimately controlled how they responded to each other. This simplified model community revealed that microbial interactions are context-specific and different environmental conditions dictate how interspecies partnerships will unfold.

Phenotypic responses to interspecies competition and commensalism in a naturally-derived microbial co-culture

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

Khan, Nymul; Maezato, Yukari; McClure, Ryan S.

The fundamental question of whether different microbial species will co-exist or compete in a given environment depends on context, composition and environmental constraints. Model microbial systems can yield some general principles related to this question. In this study we employed a naturally occurring co-culture composed of heterotrophic bacteria, Halomonas sp. HL-48 and Marinobacter sp. HL-58, to ask two fundamental scientific questions: 1) how do the phenotypes of two naturally co-existing species respond to partnership as compared to axenic growth? and 2) how do growth and molecular phenotypes of these species change with respect to competitive and commensal interactions? We hypothesizedmore » – and confirmed – that co-cultivation under glucose as the sole carbon source would result in a competitive interactions. Similarly, when glucose was swapped with xylose, the interactions became commensal because Marinobacter HL-58 was supported by metabolites derived from Halomonas HL-48. Each species responded to partnership by changing both its growth and molecular phenotype as assayed via batch growth kinetics and global transcriptomics. These phenotypic responses depended nutrient availability and so the environment ultimately controlled how they responded to each other. This simplified model community revealed that microbial interactions are context-specific and different environmental conditions dictate how interspecies partnerships will unfold.« less

Chemical synthesis, NMR analysis and evaluation on a cancer xenograft model (HL-60) of the aminosteroid derivative RM-133.

PubMed

Maltais, René; Hospital, Audrey; Delhomme, Audrey; Roy, Jenny; Poirier, Donald

2014-04-01

The aminosteroid derivative RM-133 has been reported to be a promising pro-apoptotic agent showing activity on various cancer cell lines. Following the development of solid-phase synthesis that generated a series of libraries of aminosteroid derivatives, we now report the development of a convenient liquid phase chemical synthesis of RM-133, the most promising candidate, in order to obtain sufficient quantities to proceed with the first preclinical assays. A simple and convergent six-step synthesis was designed and allowed the preparation of a gram-quantity scale of RM-133. This aminosteroid derivative was also fully characterized by NMR experiments which revealed an interesting mixture of conformers. Finally, the in vivo potency of RM-133 was evaluated on a xenograft model in nude mice with HL-60 tumors, which has resulted in the blocking of tumor progression by 57%. Copyright © 2014 Elsevier Inc. All rights reserved.

In vitro anticancer property of a novel thalidomide analogue through inhibition of NF-kappaB activation in HL-60 cells.

PubMed

Li, Min; Sun, Wan; Yang, Ya-ping; Xu, Bo; Yi, Wen-yuan; Ma, Yan-xia; Li, Zhong-jun; Cui, Jing-rong

2009-01-01

To investigate the anticancer property and possible mechanism of action of a novel sugar-substituted thalidomide derivative (STA-35) on HL-60 cells in vitro. TNF-alpha-induced NF-kappaB activation was determined using a reporter gene assay. The MTT assay was used to measure cytotoxicity of the compound. The appearance of apoptotic Sub-G1 cells was detected by flow cytometry analysis. PARP cleavage and protein expression of NF-kappaB p65 and its inhibitor IkappaB were viewed by Western blotting. TA-35 (1-20 micromol/L) suppressed TNF-alpha-induced NF-kappaB activation in transfected cells (HEK293/pNiFty-SEAP) in a dose- (1-20 micromol/L) and time-dependent (0-48 h) manner. It was also shown that STA-35 exerted a dose-dependent inhibitory effect on HL-60 cell proliferation with an IC(50) value of 9.05 micromol/L. In addition, STA-35 induced apoptosis in HL-60 cells, as indicated by the appearance of a Sub-G1 peak in the cell cycle distribution, as well as poly ADP-ribose polymerase (PARP) cleavage. Subsequently, both NF-kappaB p65 and its inhibitor IkappaB gradually accumulated in cytoplasmic extracts in a dose- and time-dependent manner, indicating the blockage of NF-kappaB translocation induced by TNF-alpha from the cytoplasm to the nucleus. A novel sugar-substituted thalidomide derivative, STA-35, is potent toward HL-60 cells in vitro and induces apoptosis by the suppression of NF-kappaB activation.

Maternal intake of cashew nuts accelerates reflex maturation and facilitates memory in the offspring.

PubMed

de Melo, Marília Ferreira Frazão Tavares; Pereira, Diego Elias; Sousa, Morgana Moura; Medeiros, Dilian Maise Ferreira; Lemos, Leanderson Tulio Marques; Madruga, Marta Suely; Santos, Nayane Medeiros; de Oliveira, Maria Elieidy Gomes; de Menezes, Camila Carolina; Soares, Juliana Késsia Barbosa

2017-10-01

Essential fatty acids, being indispensable during the stages of pregnancy, lactation and infancy influence the transmission of nerve impulses and brain function, and cashew nuts are a good source of these fatty acids. The objective of this study was to evaluate the effects of cashew nut consumption on reflex development, memory and profile of fatty acids of rat offspring treated during pregnancy and lactation. The animals were divided into three groups: Control (CONT), treated with 7% lipid derived from soybean oil; Normolipidic (NL) treated with 7% lipids derived from cashew nuts; and Hyperlipidic (HL) treated with 20% lipids derived from cashew nuts. Reflex ontogeny, Open-field habituation test and the Object Recognition Test (ORT) were assessed. The profile of fatty acids in the brain was carried out when the animals were zero, 21 and 60days old. Accelerated reflex maturation was observed in animals treated with cashew nuts (p<0.05). NL presented better memory in the Open-field habituation test; the NL and HL showed improvement of short-term memory in the ORT, but long term damage in HL (p<0.05). The results of the lipid profile of the brain at the end of the experiment showed an increase in levels of saturated fatty acids and less Docosahexaenoic acid (DHA) in animals of the HL. The data showed that maternal consumption of cashew nuts can accelerate reflex maturation and facilitate memory in offspring when offered in adequate quantities. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Derivation and Validation of the Surgical Site Infections Risk Model Using Health Administrative Data.

PubMed

van Walraven, Carl; Jackson, Timothy D; Daneman, Nick

2016-04-01

OBJECTIVE Surgical site infections (SSIs) are common hospital-acquired infections. Tracking SSIs is important to monitor their incidence, and this process requires primary data collection. In this study, we derived and validated a method using health administrative data to predict the probability that a person who had surgery would develop an SSI within 30 days. METHODS All patients enrolled in the National Surgical Quality Improvement Program (NSQIP) from 2 sites were linked to population-based administrative datasets in Ontario, Canada. We derived a multivariate model, stratified by surgical specialty, to determine the independent association of SSI status with patient and hospitalization covariates as well as physician claim codes. This SSI risk model was validated in 2 cohorts. RESULTS The derivation cohort included 5,359 patients with a 30-day SSI incidence of 6.0% (n=118). The SSI risk model predicted the probability that a person had an SSI based on 7 covariates: index hospitalization diagnostic score; physician claims score; emergency visit diagnostic score; operation duration; surgical service; and potential SSI codes. More than 90% of patients had predicted SSI risks lower than 10%. In the derivation group, model discrimination and calibration was excellent (C statistic, 0.912; Hosmer-Lemeshow [H-L] statistic, P=.47). In the 2 validation groups, performance decreased slightly (C statistics, 0.853 and 0.812; H-L statistics, 26.4 [P=.0009] and 8.0 [P=.42]), but low-risk patients were accurately identified. CONCLUSION Health administrative data can effectively identify postoperative patients with a very low risk of surgical site infection within 30 days of their procedure. Records of higher-risk patients can be reviewed to confirm SSI status.

Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients.

PubMed

Gimbrone, Nicholas T; Sarcar, Bhaswati; Gordian, Edna R; Rivera, Jason I; Lopez, Christian; Yoder, Sean J; Teer, Jamie K; Welsh, Eric A; Chiappori, Alberto A; Schabath, Matthew B; Reuther, Gary W; Dutil, Julie; Garcia, Miosotis; Ventosilla-Villanueva, Ronald; Vera-Valdivia, Luis; Yabar-Berrocal, Alejandro; Motta-Guerrero, Rodrigo; Santiago-Cardona, Pedro G; Muñoz-Antonia, Teresita; Cress, W Douglas

2017-12-01

To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from H/L patients. This retrospective observational study examined lung cancer tumor samples from 163 H/L patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, serine/threonine kinase 11 gene [STK11], and tumor protein p53 gene [TP53]) and ancestry analysis. Mutation frequencies in this H/L cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients and correlated with ancestry, sex, smoking status, and tumor histologic type. Of the adenocarcinomas in the H/L cohort (n = 120), 31% had EGFR mutations, versus 17% in the NHW control group (p < 0.001). KRAS (20% versus 38% [p = 0.002]) and STK11 (8% versus 16% [p = 0.065]) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% versus 40% [p = 0.355]) in H/L and NHW patients, respectively. Within the Hispanic cohort, ancestry influenced the rate of TP53 mutations (p = 0.009) and may have influenced the rate of EGFR, KRAS, and STK11 mutations. Driver mutations in H/L patients with lung adenocarcinoma differ in frequency from those in NHW patients associated with their indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the H/L population. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In vitro cytotoxic activity evaluation of phenytoin derivatives against human leukemia cells.

PubMed

Śladowska, Katarzyna; Handzlik, Jadwiga; Kieć-Kononowicz, Katarzyna; Mazur, Lidia

2016-09-01

Hydantoin derivatives, including phenytoin (5,5-diphenylhydantoin), have recently gained attention as they possess a variety of important biochemical and pharmacological properties. Nevertheless, available information on anticancer activity of hydantoin derivatives is still scarce. Here, we evaluated possible antileukemic potential of four phenytoin analogs, namely: methyl 2-(2,4-dioxo-5,5-diphenylimidazolidin-3-yl)propanoate (1), methyl 2-(1-(3-bromopropyl)-2,4-dioxo-5,5-diphenylimidazolidin-3-yl)propanoate (2), 1-(3-bromopropyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione (3) and 1-(3-bromobutyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione (4). The experiments were performed on human acute histiocytic lymphoma U937 cells and human promyelocytic leukemia HL-60 cells. The present study was conducted using spectrophotometric 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay and the electronic Beckman-Coulter method. We observed temporary changes in the leukemia cell viability, volume and count. The effects of the four 5,5-diphenylhydantoin derivatives on U937 and HL-60 cells depended on the agent tested and its concentration, the time intervals after the compound application, and the leukemia cell line used. HL-60 cells were more sensitive than U937 cells to the action of the phenytoin analogs (1-4). The antileukemic activities of the three bromoalkyl diphenylhydantoin derivatives (2, 3, and 4) were stronger than that of the compound 1 [methyl 2-(2,4-dioxo-5,5-diphenylimidazolidin-3-yl) propanoate], with no bromoalkyl substituent. The structural modifications of 5,5-diphenylhydantoin are responsible for such varied antileukemic potential of its four derivatives.

Improved viability and activity of neutrophils differentiated from HL-60 cells by co-culture with adipose tissue-derived mesenchymal stem cells.

PubMed

Park, Yoon Shin; Lim, Goh-Woon; Cho, Kyung-Ah; Woo, So-Youn; Shin, Meeyoung; Yoo, Eun-Sun; Chan Ra, Jeong; Ryu, Kyung-Ha

2012-06-22

Neutropenia is a principal complication of cancer treatment. We investigated the supportive effect of adipose tissue-derived mesenchymal stem cells (AD-MSCs) on the viability and function of neutrophils. Neutrophils were derived from HL-60 cells by dimethylformamide stimulation and cultured with or without AD-MSCs under serum-starved conditions to evaluate neutrophil survival, proliferation, and function. Serum starvation resulted in the apoptosis of neutrophils and decreased cell survival. The co-culture of neutrophils and AD-MSCs resulted in cell survival and inhibited neutrophil apoptosis under serum-starved conditions. The survival rate of neutrophils was prolonged up to 72 h, and the expression levels of interferon (IFN)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, and transforming growth factor (TGF)-β in AD-MSCs were increased after co-culture with neutrophils. AD-MSCs promoted the viability of neutrophils by inhibiting apoptosis as well as enhancing respiratory burst, which could potentially be mediated by the increased expression of IFN-α, G-CSF, and TGF-β. Thus, we conclude that the use of AD-MSCs may be a promising cell-based therapy for increasing immunity by accelerating neutrophil function. Copyright © 2012 Elsevier Inc. All rights reserved.

Synthesis, characterization and anticancer studies of Ni(II), Pd(II) and Pt(II) complexes with Schiff base derived from N-methylhydrazinecarbothioamide and 2-hydroxy-5-methoxy-3-nitrobenzaldehyde

NASA Astrophysics Data System (ADS)

Arafath, Md. Azharul; Adam, Farook; Razali, Mohd. R.; Ahmed Hassan, Loiy E.; Ahamed, Mohamed B. Khadeer; Majid, Amin Malik S. A.

2017-02-01

A carbothioamide NSO tridentate Schiff base ligand (HL) and its square planar complexes Na[NiLOAc], Na[PdLOAc] and [PtLdmso] have been synthesized and characterized on the basis of melting point, elemental analysis, FT-IR, 1H NMR, 13C NMR, UV-Vis spectra. The structure of HL was elucidated with X-ray diffraction analysis. In the present study, the synthesized compounds were evaluated for their anticancer properties against three human cancer cell lines breast cancer (MCF-7), cervical (Hela), and colon (HCT-116). In addition, the cytotoxicity of the synthesized compounds was tested on a normal human cell line (human endothelial cell line EA.hy926). Among the tested compounds, the complex [NiLOAc] excelled in halting proliferation of the cervical and colon cancer cells with median inhibitory concentration (IC50) values of 28.33 and 34.4 μM, respectively. The complex, [PdLOAc] demonstrated selective cytotoxicity against breast cancer line MCF-7 with IC50 = 47.5 μM, while HL showed inhibitory effect against colon cancer cell line (HCT-116) with IC50 = 55.66 μM. The complex, [PtLdmso] showed mild activity against breast cancer (MCF-7) and cervical cancer (Hela) cells with IC50 = 64.44 and 68.3 μM, respectively, whereas, it displayed insignificant cytotoxicity against human endothelial cells (EA.hy926) with IC50 > 200 μM. Cancer cells treated with [NiLOAc] showed apoptotic features such as membrane blebbing and DNA condensation. Thus, the findings of the present study demonstrated that the series of metal complexes of HL could form the new lead for development of cancer chemotherapies to treat human cervical, breast and colon malignancies.

Rhenium(I) tricarbonyl compounds of bioactive thiosemicarbazones: Synthesis, characterization and activity against Trypanosoma cruzi.

PubMed

Rodríguez Arce, Esteban; Machado, Ignacio; Rodríguez, Belén; Lapier, Michel; Zúñiga, María Carolina; Maya, Juan Diego; Olea Azar, Claudio; Otero, Lucía; Gambino, Dinorah

2017-05-01

American Trypanosomiasis is a chronic infection discovered and described in 1909 by the Brazilian scientist Carlos Chagas. It is caused by the protozoan parasite Trypanosoma cruzi. Although it affects about 10million people in Latin America, the current chemotherapy is still inadequate. The discovery of new drugs is urgently needed. Our group is focused on the development of prospective metal-based drugs mainly based on bioactive ligands and pharmacologically interesting metal ions. In this work three new rhenium(I) tricarbonyl compounds fac-[Re I (CO) 3 Br(HL)] where HL=5-nitrofuryl containing thiosemicarbazones were synthesized and fully characterized in solution and in the solid state. The in vitro evaluation of the compounds on T. cruzi trypomastigotes (Dm28c strain) showed that the Re(I) compounds are 8 to 15 times more active than the reference drug Nifurtimox and show a 4 to 17 fold increase in activity in respect to the free (HL) ligands. Obtained compounds also show good selectivity indexes (IC 50 endothelial cells Ea.hy926 /IC 50 T. cruzi (Dm28c tripomastigotes) ). 1 H NMR and MS studies, performed with time, showed that the fac-[Re(CO) 3 Br(HL)] species convert into the dimers [Re 2 (CO) 6 (L) 2 ] in solution. Crystal structure of [Re I 2 (CO) 6 (L2) 2 ], the product of complexes' dimerization, was solved. Related to the mechanism of action, the studied compounds do not generate radical oxygen species in the parasite (as 5-nitrofuryl derived thiosemicarbazones do) probably due to the unfavorable nitro reduction potential of the generated dimeric species. On the contrary, the compounds produce a decrease of the oxygen consumption rate of the parasites, maybe inhibiting their mitochondrial respiration. Copyright © 2017 Elsevier Inc. All rights reserved.

Personalized-detailed clinical model for data interoperability among clinical standards.

PubMed

Khan, Wajahat Ali; Hussain, Maqbool; Afzal, Muhammad; Amin, Muhammad Bilal; Saleem, Muhammad Aamir; Lee, Sungyoung

2013-08-01

Data interoperability among health information exchange (HIE) systems is a major concern for healthcare practitioners to enable provisioning of telemedicine-related services. Heterogeneity exists in these systems not only at the data level but also among different heterogeneous healthcare standards with which these are compliant. The relationship between healthcare organization data and different heterogeneous standards is necessary to achieve the goal of data level interoperability. We propose a personalized-detailed clinical model (P-DCM) approach for the generation of customized mappings that creates the necessary linkage between organization-conformed healthcare standards concepts and clinical model concepts to ensure data interoperability among HIE systems. We consider electronic health record (EHR) standards, openEHR, and HL7 CDA instances transformation using P-DCM. P-DCM concepts associated with openEHR and HL7 CDA help in transformation of instances among these standards. We investigated two datasets: (1) data of 100 diabetic patients, including 50 each of type 1 and type 2, from a local hospital in Korea and (2) data of a single Alzheimer's disease patient. P-DCMs were created for both scenarios, which provided the basis for deriving instances for HL7 CDA and openEHR standards. For proof of concept, we present case studies of encounter information for type 2 diabetes mellitus patients and monitoring of daily routine activities of an Alzheimer's disease patient. These reflect P-DCM-based customized mappings generation with openEHR and HL7 CDA standards. Customized mappings are generated based on the relationship of P-DCM concepts with CDA and openEHR concepts. The objective of this work is to achieve semantic data interoperability among heterogeneous standards. This would lead to effective utilization of resources and allow timely information exchange among healthcare systems.

Personalized-Detailed Clinical Model for Data Interoperability Among Clinical Standards

PubMed Central

Khan, Wajahat Ali; Hussain, Maqbool; Afzal, Muhammad; Amin, Muhammad Bilal; Saleem, Muhammad Aamir

2013-01-01

Abstract Objective: Data interoperability among health information exchange (HIE) systems is a major concern for healthcare practitioners to enable provisioning of telemedicine-related services. Heterogeneity exists in these systems not only at the data level but also among different heterogeneous healthcare standards with which these are compliant. The relationship between healthcare organization data and different heterogeneous standards is necessary to achieve the goal of data level interoperability. We propose a personalized-detailed clinical model (P-DCM) approach for the generation of customized mappings that creates the necessary linkage between organization-conformed healthcare standards concepts and clinical model concepts to ensure data interoperability among HIE systems. Materials and Methods: We consider electronic health record (EHR) standards, openEHR, and HL7 CDA instances transformation using P-DCM. P-DCM concepts associated with openEHR and HL7 CDA help in transformation of instances among these standards. We investigated two datasets: (1) data of 100 diabetic patients, including 50 each of type 1 and type 2, from a local hospital in Korea and (2) data of a single Alzheimer's disease patient. P-DCMs were created for both scenarios, which provided the basis for deriving instances for HL7 CDA and openEHR standards. Results: For proof of concept, we present case studies of encounter information for type 2 diabetes mellitus patients and monitoring of daily routine activities of an Alzheimer's disease patient. These reflect P-DCM-based customized mappings generation with openEHR and HL7 CDA standards. Customized mappings are generated based on the relationship of P-DCM concepts with CDA and openEHR concepts. Conclusions: The objective of this work is to achieve semantic data interoperability among heterogeneous standards. This would lead to effective utilization of resources and allow timely information exchange among healthcare systems. PMID:23875730

3-Hydroxy-3-methylglutaryl CoA lyase (HL): Mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients

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

Wang, S.P.; Robert, M.F.; Mitchell, G.A.

1996-04-01

3-hydroxy-3-methylglutaryl CoA lyase (HL, EC 4.1.3.4) catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetic acid and acetyl CoA, the final reaction of both ketogenesis and leucine catabolism. Autosomal-recessive HL deficiency in humans results in episodes of hypoketotic hypoglycemia and coma. Using a mouse HL cDNA as a probe, we isolated a clone containing the full-length mouse HL gene that spans about 15 kb of mouse chromosome 4 and contains nine exons. The promoter region of the mouse HL gene contains elements characteristic of a housekeeping gene: a CpG island containing multiple Sp1 binding sites surrounds exon 1, and neither amore » TATA nor a CAAT box are present. We identified multiple transcription start sites in the mouse HL gene, 35 to 9 bases upstream of the translation start codon. We also isolated two human HL genomic clones that include HL exons 2 to 9 within 18 kb. The mouse and human HL genes (HGMW-approved symbol HMGCL) are highly homologous, with identical locations of intron-exon junctions. By genomic Southern blot analysis and exonic PCR, was found 2 of 33 HL-deficient probands to be homozygous for large deletions in the HL gene. 26 refs., 4 figs., 2 tabs.« less

[Primary study on fluro [ 19F] berberine derivative for human hepatocellular carcinoma targetting in vitro].

PubMed

Zhang, Tong; Wu, Xiaoai; Cai, Huawei; Liang, Meng; Fan, Chengzhong

2017-04-01

[ 18 F]HX-01, a Fluorine-18 labeled berberine derivative, is a potential positron emission tomography (PET) tumor imaging agent, while [ 19 F]HX-01 is a nonradioactive reference substance with different energy state and has the same physical and chemical properties. In order to collect data for further study of [ 18 F]HX-01 PET imaging of hepatocellular carcinoma in vivo , this study compared the uptake of [ 19 F]HX-01 by human hepatocellular carcinoma and normal hepatocytes in vitro . The target compound, [ 19 F]HX-01, was synthesized in one step using berberrubine and 3-fluoropropyl 4-methylbenzenesulfonate. Cellular uptake and localization of [ 19 F]HX-01 were performed by a fluorescence microscope in human hepatocellular carcinoma HepG2, SMMC-7721 and human normal hepatocyte HL-7702. Cellular proliferation inhibition and cell cytotoxicity assay of the [ 19 F]HX-01 were conducted using cell counting kit-8 (CCK-8) on HepG2, SMMC-7721 and HL-7702 cells. Fluorescent microscopy showed that the combining ability of [ 19 F]HX-01 to the carcinoma SMMC-7721 and HepG2 was higher than that to the normal HL-7702. Cellular proliferation inhibition assay demonstrated that [ 19 F]HX-01 leaded to a dose-dependent inhibition on SMMC-7721, HepG2, and HL-7702 proliferation. Cell cytotoxicity assay presented that the cytotoxicity of [ 19 F]HX-01 to SMMC-7721 and HepG2 was obviously higher than that to HL-7702. This in vitro study showed that [ 19 F]HX-01 had a higher selectivity on human hepatocellular carcinoma cells (SMMC-7721, HepG2) but has less toxicity to normal hepatocytes (HL-7702). This could set up the idea that the radioactive reference substance [ 18 F]HX-01 may be worthy of further development as a potential molecular probe targeting human hepatocellular carcinoma using PET.

Health Literacy among Youth in Guatemala City.

PubMed

Hoffman, Steven; Marsiglia, Flavio F; Nevarez, Lucinda; Porta, Maria

2017-01-02

Health literacy (HL) is recognized as an important health construct that is correlated with various health-related outcomes, but outside of the United States there is limited HL research available, particularly among youth. This study looked at the HL and harmful health behavior (i.e., substance use) of 210 youth across 10 schools in Guatemala City. Based on results from the Newest Vital Sign (NVS) HL assessment, fewer than one third of youth sampled had adequate HL. Training/education to improve adolescent HL is needed in Guatemala City, and the unique skillset of social workers could be an idea method of reaching at-risk youth.

Bridging the Gap between HL7 CDA and HL7 FHIR: A JSON Based Mapping.

PubMed

Rinner, Christoph; Duftschmid, Georg

2016-01-01

The Austrian electronic health record (EHR) system ELGA went live in December 2016. It is a document oriented EHR system and is based on the HL7 Clinical Document Architecture (CDA). The HL7 Fast Healthcare Interoperability Resources (FHIR) is a relatively new standard that combines the advantages of HL7 messages and CDA Documents. In order to offer easier access to information stored in ELGA we present a method based on adapted FHIR resources to map CDA documents to FHIR resources. A proof-of-concept tool using Java, the open-source FHIR framework HAPI-FHIR and publicly available FHIR servers was created to evaluate the presented mapping. In contrast to other approaches the close resemblance of the mapping file to the FHIR specification allows existing FHIR infrastructure to be reused. In order to reduce information overload and facilitate the access to CDA documents, FHIR could offer a standardized way to query CDA data on a fine granular base in Austria.

Applicability of Hydrologic Landscapes for Model Calibration ...

EPA Pesticide Factsheets

The Pacific Northwest Hydrologic Landscapes (PNW HL) at the assessment unit scale has provided a solid conceptual classification framework to relate and transfer hydrologically meaningful information between watersheds without access to streamflow time series. A collection of techniques were applied to the HL assessment unit composition in watersheds across the Pacific Northwest to aggregate the hydrologic behavior of the Hydrologic Landscapes from the assessment unit scale to the watershed scale. This non-trivial solution both emphasizes HL classifications within the watershed that provide that majority of moisture surplus/deficit and considers the relative position (upstream vs. downstream) of these HL classifications. A clustering algorithm was applied to the HL-based characterization of assessment units within 185 watersheds to help organize watersheds into nine classes hypothesized to have similar hydrologic behavior. The HL-based classes were used to organize and describe hydrologic behavior information about watershed classes and both predictions and validations were independently performed with regard to the general magnitude of six hydroclimatic signature values. A second cluster analysis was then performed using the independently calculated signature values as similarity metrics, and it was found that the six signature clusters showed substantial overlap in watershed class membership to those in the HL-based classes. One hypothesis set forward from thi

Oxidative DNA damage induced by a hydroperoxide derivative of cyclophosphamide.

PubMed

Murata, Mariko; Suzuki, Toshinari; Midorikawa, Kaoru; Oikawa, Shinji; Kawanishi, Shosuke

2004-09-15

Interstrand DNA cross-linking has been considered to be the primary action mechanism of cyclophosphamide (CP) and its hydroperoxide derivative, 4-hydroperoxycyclophosphamide (4-HC). To clarify the mechanism of anti-tumor effects by 4-HC, we investigated DNA damage in a human leukemia cell line, HL-60, and its H(2)O(2)-resistant clone HP100. Apoptosis DNA ladder formation was detected in HL-60 cells treated with 4-HC, whereas it was not observed in HP100 cells. 4-HC significantly increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, a marker of oxidative DNA damage, in HL-60 cells. On the other hand, CP did not significantly induce 8-oxodG formation and apoptosis in HL-60 cells under the same conditions as did 4-HC. Using (32)P-labeled DNA fragments from the human p53 tumor suppressor gene, 4-HC was found to cause Cu(II)-mediated oxidative DNA damage, but CP did not. Catalase inhibited 4-HC-induced DNA damage, including 8-oxodG formation, suggesting the involvement of H(2)O(2). The generation of H(2)O(2) during 4-HC degradation was ascertained by procedures using scopoletin and potassium iodide. We conclude that, in addition to DNA cross-linking, oxidative DNA damage through H(2)O(2) generation may participate in the anti-tumor effects of 4-HC.

Palladium(II) complexes with N-heteroaromatic bidentate hydrazone ligands: the effect of the chelate ring size and lipophilicity on in vitro cytotoxic activity.

PubMed

Filipović, Nenad; Grubišić, Sonja; Jovanović, Maja; Dulović, Marija; Marković, Ivanka; Klisurić, Olivera; Marinković, Aleksandar; Mitić, Dragana; Anđelković, Katarina; Todorović, Tamara

2014-09-01

Novel Pd(II) complex with N-heteroaromatic Schiff base ligand, derived from 8-quinolinecarboxaldehyde (q8a) and ethyl hydrazinoacetate (haOEt), was synthesized and characterized by analytical and spectroscopy methods. The structure of novel complex, as well as structures of its quinoline and pyridine analogues, was optimized by density functional theory calculations, and theoretical data show good agreement with experimental results. A cytotoxic action of the complexes was evaluated on cultures of human promyelocytic leukemia (HL-60), human glioma (U251), rat glioma (C6), and mouse fibrosarcoma (L929) cell lines. Among investigated compounds, only complexes with quinoline-based ligands reduce the cell numbers in a dose-dependent manner in investigated cell lines. The observed cytotoxic effect of two isomeric quinoline-based complexes is predominantly mediated through the induction of apoptotic cell death in HL-60 cell line. The cytotoxicity of most efficient novel Pd(II) complex is comparable to the activity of cisplatin, in all cell lines investigated. © 2014 John Wiley & Sons A/S.

Differentiation-inducing effects of small fruit juices on HL-60 leukemic cells.

PubMed

Yoshizawa, Y; Kawaii, S; Urashima, M; Fukase, T; Sato, T; Murofushi, N; Nishimura, H

2000-08-01

Epidemiological studies indicate that high intakes of fruits and vegetables are associated with a reduced risk of cancer, and several plant-derived drugs have been developed in medical oncology. Since only a small part of the flora has been tested for any kind of bioactivity, we chose small fruits as sources of differentiation-inducing activity against HL-60 leukemic cells. We have prepared juices from various small fruits that grow mainly in the northern part of Japan. Screening of 43 samples indicated that juices of Actinidia polygama Maxim., Rosa rugosa Thunb., Vaccinium smallii A. Gray, and Sorbus sambucifolia Roem. strongly induced differentiation of HL-60 cells to monocyte/macrophage characteristics in a concentration-dependent manner as indicated by histochemical and biochemical examinations.

Childhood vision impairment, hearing loss and co-occurring autism spectrum disorder

PubMed Central

Kancherla, Vijaya; Van Naarden Braun, Kim; Yeargin-Allsopp, Marshalyn

2015-01-01

Background Limited population-based data on prevalence of childhood vision impairment (VI) and hearing loss (HL), and their co-occurrence with autism spectrum disorder (ASD) exists. Objective To examine prevalence and characteristics of VI, HL and co-occurring ASD among 8-year-olds in metropolitan Atlanta 2000–2008. Methods We used data from the population-based Metropolitan Atlanta Developmental Disabilities Surveillance Program. Prevalence, birth and parental characteristics, presence and severity of other co-occurring developmental disabilities, and age of earliest identification of ASD, were examined for children with VI and HL, by co-occurring ASD. Results VI and HL prevalences were 1.2 and 1.3 per 1000 8-year-olds, respectively. Approximately 6–7% of children with VI or HL had co-occurring ASD. Children with VI or HL with co-occurring ASD differed from those without co-occurring ASD by select birth characteristics and the presence of other co-occurring DDs. The median age of earliest known ASD diagnosis was significantly later among children with VI and ASD compared to children with ASD without VI (79 vs. 56 months). Children with HL and ASD were first evaluated by a community provider significantly earlier than those with ASD without HL (40 vs. 50 months). Conclusions The frequency of co-occurring ASD with VI and HL is higher than the population prevalence of ASD. The significant delays in diagnosis of ASD in children with VI and lack of earlier diagnosis of ASD among children with HL despite earlier evaluation highlight the importance of developing screening tools for early identification of ASD among children with VI and HL. PMID:24060256

Applying a Particle-only Model to the HL Tau Disk

NASA Astrophysics Data System (ADS)

Tabeshian, Maryam; Wiegert, Paul A.

2018-04-01

Observations have revealed rich structures in protoplanetary disks, offering clues about their embedded planets. Due to the complexities introduced by the abundance of gas in these disks, modeling their structure in detail is computationally intensive, requiring complex hydrodynamic codes and substantial computing power. It would be advantageous if computationally simpler models could provide some preliminary information on these disks. Here we apply a particle-only model (that we developed for gas-poor debris disks) to the gas-rich disk, HL Tauri, to address the question of whether such simple models can inform the study of these systems. Assuming three potentially embedded planets, we match HL Tau’s radial profile fairly well and derive best-fit planetary masses and orbital radii (0.40, 0.02, 0.21 Jupiter masses for the planets orbiting a 0.55 M ⊙ star at 11.22, 29.67, 64.23 au). Our derived parameters are comparable to those estimated by others, except for the mass of the second planet. Our simulations also reproduce some narrower gaps seen in the ALMA image away from the orbits of the planets. The nature of these gaps is debated but, based on our simulations, we argue they could result from planet–disk interactions via mean-motion resonances, and need not contain planets. Our results suggest that a simple particle-only model can be used as a first step to understanding dynamical structures in gas disks, particularly those formed by planets, and determine some parameters of their hidden planets, serving as useful initial inputs to hydrodynamic models which are needed to investigate disk and planet properties more thoroughly.

The evolving role of targeted drugs in the treatment of Hodgkin lymphoma.

PubMed

Eichenauer, Dennis A; Engert, Andreas

2017-09-01

Hodgkin lymphoma (HL) is a B-cell-derived malignancy mostly affecting young adults. More than 80% of patients are cured after stage-adapted first-line treatment with chemotherapy and/or radiotherapy. About 50% of patients with disease recurrence achieve long-term remission with second-line treatment consisting of high-dose chemotherapy and autologous stem cell transplantation. However, HL treatment is often associated with acute toxicity and in part life-threatening late effects. Implementing targeted drugs may reduce toxicity and potentially further optimize efficacy. In recent years, the CD30-directed antibody-drug conjugate brentuximab vedotin (BV) and anti-PD-1 antibodies, nivolumab and pembrolizumab, underwent extensive evaluation in HL. They have exhibited encouraging single agent activity and a favorable toxicity profile in patients with multiple relapses. Therefore, they are currently under investigation in different additional indications. Areas covered: This article gives an overview over clinical trials evaluating targeted drugs either as single agent or as part of combination therapies in HL patients. Expert commentary: A multitude of targeted drugs are investigated in HL. Promising data have particularly emerged from studies with BV and anti-PD-1 antibodies. However, mature data needed for final conclusions are still pending.

Stability of singularity-free cosmological solutions in Hořava-Lifshitz gravity

NASA Astrophysics Data System (ADS)

Misonoh, Yosuke; Fukushima, Mitsuhiro; Miyashita, Shoichiro

2017-02-01

We study the stability of singularity-free cosmological solutions with a positive cosmological constant based on the projectable Hořava-Lifshitz (HL) theory. In the HL theory, the isotropic and homogeneous cosmological solutions with bounce can be realized if the spatial curvature is nonzero. By performing a perturbation analysis around nonflat Friedmann-Lemaître-Robertson-Walker (FLRW) spacetime, we derive a quadratic action and discuss the stability, i.e., ghost and tachyon-free conditions. Although the squared effective mass of scalar perturbation must be negative in the infrared regime, we can avoid tachyon instability by considering strong Hubble friction. Additionally, we estimate the backreaction from the perturbations on the background geometry, especially against an anisotropic perturbation in closed FLRW spacetime. It turns out that certain types of bouncing solution may be spoiled even if all perturbation modes are stable.

Low-dose chest computed tomography for lung cancer screening among Hodgkin lymphoma survivors: a cost-effectiveness analysis.

PubMed

Wattson, Daniel A; Hunink, M G Myriam; DiPiro, Pamela J; Das, Prajnan; Hodgson, David C; Mauch, Peter M; Ng, Andrea K

2014-10-01

Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs. LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening may be cost effective for all smokers but possibly not for nonsmokers despite a small life expectancy benefit. Copyright © 2014 Elsevier Inc. All rights reserved.

Dibenzoyl and isoflavonoid glycosides from Sophora flavescens: inhibition of the cytotoxic effect of D-galactosamine on human hepatocyte HL-7702.

PubMed

Shen, Yi; Feng, Zi-Ming; Jiang, Jian-Shuang; Yang, Ya-Nan; Zhang, Pei-Cheng

2013-12-27

Twelve new dibenzoyl derivatives sophodibenzoside A-L (1-12) and five new isoflavone glycosides (13-17) have been isolated from the roots of Sophora flavescens together with eight known compounds (18-25). Notably, the use of acetic acid-d4 was required to enable identification of the dibenzoyl glycoside structures. Compounds 1, 2, 13, 14, and 19 exhibited weak inhibition of the cytotoxic effect of d-galactosamine on the human hepatic cell line HL-7702.

Antibodies and antibody-drug conjugates in the treatment of Hodgkin lymphoma.

PubMed

Eichenauer, Dennis A; Engert, Andreas

2014-07-01

Hodgkin lymphoma (HL) is a B cell-derived lymphoid malignancy most often affecting young adults. More than 80% of HL patients achieve long-term remission after appropriate first-line treatment consisting of multiagent chemotherapy and/or radiotherapy (RT). In addition, approximately 50% of patients with disease recurrence remain relapse-free after salvage therapy with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). However, patients with multiple relapses are mostly in a palliative situation, and novel drugs for this patient group are needed. Furthermore, novel less toxic but equally effective first-line and second-line approaches are required as therapy-related late sequelae represent a relevant cause of morbidity and mortality in HL survivors. Several antibodies and antibody-drug conjugates (ADC) targeting CD30 and CD20 have recently been evaluated in HL. Excellent response rates in heavily pretreated patients were observed with the ADC brentuximab vedotin directed against CD30. Thus, ongoing trials investigate brentuximab vedotin in different additional indications. One example is the first-line treatment of advanced HL where the drug is currently being evaluated in combination with variants of the first-line protocols ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). Anti-CD20 antibodies given either as single agent or in combination with conventional chemotherapy have also been investigated and still undergo investigation in prospective studies including HL patients. This article reviews the available data on treatment approaches including antibodies and ADC in HL patients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Syntheses of cytotoxic novel arctigenin derivatives bearing halogen and alkyl groups on aromatic rings.

PubMed

Yamauchi, Satoshi; Wukirsari, Tuti; Ochi, Yoshiaki; Nishiwaki, Hisashi; Nishi, Kosuke; Sugahara, Takuya; Akiyama, Koichi; Kishida, Taro

2017-09-01

The new lignano-9,9'-lactones (α,β-dibenzyl-γ-butyrolactone lignans), which showed the higher cytotoxicity than arctigenin, were synthesized. The well-known cytotoxic arctigenin showed activity against HL-60 cells (EC 50 =12μM), however, it was inactive against HeLa cells (EC 50 >100μM). The synthesized (3,4-dichloro, 2'-butoxy)-derivative 55 and (3,4-dichloro, 4'-butyl)-derivative 66 bearing the lignano-9,9'-lactone structures showed the EC 50 values of 10μM and 9.4μM against HL-60 cells, respectively. Against HeLa cells, the EC 50 value of the derivative 66 was 27μM. By comparing the activities with the corresponding 9,9'-epoxy structure (tetrahydrofuran compounds), the importance of the lactone structure of 55 and 66 for the higher activities was shown. The substituents on the aromatic ring of the lignano-9,9'-lactones affected the cytotoxicity level, observing more than 10-fold difference. Copyright © 2017. Published by Elsevier Ltd.

An Improved Extrapolation Scheme for Truncated CT Data Using 2D Fourier-Based Helgason-Ludwig Consistency Conditions.

PubMed

Xia, Yan; Berger, Martin; Bauer, Sebastian; Hu, Shiyang; Aichert, Andre; Maier, Andreas

2017-01-01

We improve data extrapolation for truncated computed tomography (CT) projections by using Helgason-Ludwig (HL) consistency conditions that mathematically describe the overlap of information between projections. First, we theoretically derive a 2D Fourier representation of the HL consistency conditions from their original formulation (projection moment theorem), for both parallel-beam and fan-beam imaging geometry. The derivation result indicates that there is a zero energy region forming a double-wedge shape in 2D Fourier domain. This observation is also referred to as the Fourier property of a sinogram in the previous literature. The major benefit of this representation is that the consistency conditions can be efficiently evaluated via 2D fast Fourier transform (FFT). Then, we suggest a method that extrapolates the truncated projections with data from a uniform ellipse of which the parameters are determined by optimizing these consistency conditions. The forward projection of the optimized ellipse can be used to complete the truncation data. The proposed algorithm is evaluated using simulated data and reprojections of clinical data. Results show that the root mean square error (RMSE) is reduced substantially, compared to a state-of-the-art extrapolation method.

An Improved Extrapolation Scheme for Truncated CT Data Using 2D Fourier-Based Helgason-Ludwig Consistency Conditions

PubMed Central

Berger, Martin; Bauer, Sebastian; Hu, Shiyang; Aichert, Andre

2017-01-01

We improve data extrapolation for truncated computed tomography (CT) projections by using Helgason-Ludwig (HL) consistency conditions that mathematically describe the overlap of information between projections. First, we theoretically derive a 2D Fourier representation of the HL consistency conditions from their original formulation (projection moment theorem), for both parallel-beam and fan-beam imaging geometry. The derivation result indicates that there is a zero energy region forming a double-wedge shape in 2D Fourier domain. This observation is also referred to as the Fourier property of a sinogram in the previous literature. The major benefit of this representation is that the consistency conditions can be efficiently evaluated via 2D fast Fourier transform (FFT). Then, we suggest a method that extrapolates the truncated projections with data from a uniform ellipse of which the parameters are determined by optimizing these consistency conditions. The forward projection of the optimized ellipse can be used to complete the truncation data. The proposed algorithm is evaluated using simulated data and reprojections of clinical data. Results show that the root mean square error (RMSE) is reduced substantially, compared to a state-of-the-art extrapolation method. PMID:28808441

Transfected Babesia bovis Expressing a Tick GST as a Live Vector Vaccine

PubMed Central

Oldiges, Daiane P.; Laughery, Jacob M.; Tagliari, Nelson Junior; Leite Filho, Ronaldo Viana; Davis, William C.; da Silva Vaz, Itabajara; Termignoni, Carlos; Knowles, Donald P.; Suarez, Carlos E.

2016-01-01

The Rhipicephalus microplus tick is a notorious blood-feeding ectoparasite of livestock, especially cattle, responsible for massive losses in animal production. It is the main vector for transmission of pathogenic bacteria and parasites, including Babesia bovis, an intraerythrocytic apicomplexan protozoan parasite responsible for bovine Babesiosis. This study describes the development and testing of a live B. bovis vaccine expressing the protective tick antigen glutathione-S-transferase from Haemaphysalis longicornis (HlGST). The B. bovis S74-T3B parasites were electroporated with a plasmid containing the bidirectional Ef-1α (elongation factor 1 alpha) promoter of B. bovis controlling expression of two independent genes, the selectable marker GFP-BSD (green fluorescent protein–blasticidin deaminase), and HlGST fused to the MSA-1 (merozoite surface antigen 1) signal peptide from B. bovis. Electroporation followed by blasticidin selection resulted in the emergence of a mixed B. bovis transfected line (termed HlGST) in in vitro cultures, containing parasites with distinct patterns of insertion of both exogenous genes, either in or outside the Ef-1α locus. A B. bovis clonal line termed HlGST-Cln expressing intracellular GFP and HlGST in the surface of merozoites was then derived from the mixed parasite line HlGST using a fluorescent activated cell sorter. Two independent calf immunization trials were performed via intravenous inoculation of the HlGST-Cln and a previously described control consisting of an irrelevant transfected clonal line of B. bovis designated GFP-Cln. The control GFP-Cln line contains a copy of the GFP-BSD gene inserted into the Ef-1α locus of B. bovis in an identical fashion as the HIGST-Cln parasites. All animals inoculated with the HlGST-Cln and GFP-Cln transfected parasites developed mild babesiosis. Tick egg fertility and fully engorged female tick weight was reduced significantly in R. microplus feeding on HlGST-Cln-immunized calves. Collectively, these data show the efficacy of a transfected HlGST-Cln B. bovis parasite to induce detectable anti-glutathione-S-transferase antibodies and a reduction in tick size and fecundity of R. microplus feeding in experimentally inoculated animals. PMID:27911903

Synthesis, characterization and biological activity of some transition metals with Schiff base derived from 2-thiophene carboxaldehyde and aminobenzoic acid.

PubMed

Mohamed, Gehad G; Omar, M M; Hindy, Ahmed M M

2005-12-01

Metal complexes of Schiff base derived from 2-thiophene carboxaldehyde and 2-aminobenzoic acid (HL) are reported and characterized based on elemental analyses, IR, 1H NMR, solid reflectance, magnetic moment, molar conductance and thermal analysis (TGA). The ligand dissociation as well as the metal-ligand stability constants were calculated pH metrically at 25 degrees C and ionic strength mu=0.1 (1M NaCl). The complexes are found to have the formulae [M(HL)2](X)n.yH2O (where M=Fe(III) (X=Cl, n=3, y=3), Co(II) (X=Cl, n=2, y=1.5), Ni(II) (X=Cl, n=2, y=1) and UO2(II) (X=NO3, n=2, y=0)) and [M(L)2] (where M=Cu(II) (X=Cl) and Zn(II) (X=AcO)). The molar conductance data reveal that Fe(III) and Co(II), Ni(II) and UO2(II) chelates are ionic in nature and are of the type 3:1 and 2:1 electrolytes, respectively, while Cu(II) and Zn(II) complexes are non-electrolytes. IR spectra show that HL is coordinated to the metal ions in a terdentate manner with ONS donor sites of the carboxylate O, azomethine N and thiophene S. From the magnetic and solid reflectance spectra, it is found that the geometrical structure of these complexes are octahedral. The thermal behaviour of these chelates shows that the hydrated complexes losses water molecules of hydration in the first step followed immediately by decomposition of the anions and ligand molecules in the subsequent steps. The activation thermodynamic parameters, such as, E*, DeltaH*, DeltaS* and DeltaG* are calculated from the DrTG curves using Coats-Redfern method. The synthesized ligands, in comparison to their metal complexes also were screened for their antibacterial activity against bacterial species, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus pyogones and Fungi (Candida). The activity data show that the metal complexes to be more potent/antibacterial than the parent Schiff base ligand against one or more bacterial species.

Synthesis, characterization and biological activity of some transition metals with Schiff base derived from 2-thiophene carboxaldehyde and aminobenzoic acid

NASA Astrophysics Data System (ADS)

Mohamed, Gehad G.; Omar, M. M.; Hindy, Ahmed M. M.

2005-12-01

Metal complexes of Schiff base derived from 2-thiophene carboxaldehyde and 2-aminobenzoic acid (HL) are reported and characterized based on elemental analyses, IR, 1H NMR, solid reflectance, magnetic moment, molar conductance and thermal analysis (TGA). The ligand dissociation as well as the metal-ligand stability constants were calculated pH metrically at 25 °C and ionic strength μ = 0.1 (1 M NaCl). The complexes are found to have the formulae [M(HL) 2](X) n· yH 2O (where M = Fe(III) (X = Cl, n = 3, y = 3), Co(II) (X = Cl, n = 2, y = 1.5), Ni(II) (X = Cl, n = 2, y = 1) and UO 2(II) (X = NO 3, n = 2, y = 0)) and [M(L) 2] (where M = Cu(II) (X = Cl) and Zn(II) (X = AcO)). The molar conductance data reveal that Fe(III) and Co(II), Ni(II) and UO 2(II) chelates are ionic in nature and are of the type 3:1 and 2:1 electrolytes, respectively, while Cu(II) and Zn(II) complexes are non-electrolytes. IR spectra show that HL is coordinated to the metal ions in a terdentate manner with ONS donor sites of the carboxylate O, azomethine N and thiophene S. From the magnetic and solid reflectance spectra, it is found that the geometrical structure of these complexes are octahedral. The thermal behaviour of these chelates shows that the hydrated complexes losses water molecules of hydration in the first step followed immediately by decomposition of the anions and ligand molecules in the subsequent steps. The activation thermodynamic parameters, such as, E*, Δ H*, Δ S* and Δ G* are calculated from the DrTG curves using Coats-Redfern method. The synthesized ligands, in comparison to their metal complexes also were screened for their antibacterial activity against bacterial species, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus pyogones and Fungi (Candida). The activity data show that the metal complexes to be more potent/antibacterial than the parent Schiff base ligand against one or more bacterial species.

An HL7-CDA wrapper for facilitating semantic interoperability to rule-based Clinical Decision Support Systems.

PubMed

Sáez, Carlos; Bresó, Adrián; Vicente, Javier; Robles, Montserrat; García-Gómez, Juan Miguel

2013-03-01

The success of Clinical Decision Support Systems (CDSS) greatly depends on its capability of being integrated in Health Information Systems (HIS). Several proposals have been published up to date to permit CDSS gathering patient data from HIS. Some base the CDSS data input on the HL7 reference model, however, they are tailored to specific CDSS or clinical guidelines technologies, or do not focus on standardizing the CDSS resultant knowledge. We propose a solution for facilitating semantic interoperability to rule-based CDSS focusing on standardized input and output documents conforming an HL7-CDA wrapper. We define the HL7-CDA restrictions in a HL7-CDA implementation guide. Patient data and rule inference results are mapped respectively to and from the CDSS by means of a binding method based on an XML binding file. As an independent clinical document, the results of a CDSS can present clinical and legal validity. The proposed solution is being applied in a CDSS for providing patient-specific recommendations for the care management of outpatients with diabetes mellitus. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Dietary Pattern and Risk of Hodgkin Lymphoma in a Population-Based Case-Control Study

PubMed Central

Epstein, Mara M.; Chang, Ellen T.; Zhang, Yawei; Fung, Teresa T.; Batista, Julie L.; Ambinder, Richard F.; Zheng, Tongzhang; Mueller, Nancy E.; Birmann, Brenda M.

2015-01-01

Classic Hodgkin lymphoma (cHL) has few known modifiable risk factors, and the relationship between diet and cHL risk is unclear. We performed the first investigation of an association between dietary pattern and cHL risk in 435 cHL cases and 563 population-based controls from Massachusetts and Connecticut (1997–2000) who completed baseline diet questionnaires. We identified 4 major dietary patterns (“vegetable,” “high meat,” “fruit/low-fat dairy,” “desserts/sweets”) using principal components analysis. We computed multivariable odds ratios and 95% confidence intervals for associations of dietary pattern score (quartiles) with younger-adult (age <50 years), older-adult (age ≥50 years), and overall cHL risk. Secondary analyses examined associations by histological subtype and tumor Epstein-Barr virus (EBV) status. A diet high in desserts/sweets was associated with younger-adult (odds ratio(quartile 4 vs. quartile 1) = 1.60, 95% confidence interval: 1.05, 2.45; Ptrend = 0.008) and EBV-negative, younger-adult (odds ratio = 2.11, 95% confidence interval: 1.31, 3.41; Ptrend = 0.007) cHL risk. A high meat diet was associated with older-adult (odds ratio = 3.34, 95% confidence interval: 1.02, 10.91; Ptrend = 0.04) and EBV-negative, older-adult (odds ratio = 4.64, 95% confidence interval: 1.03, 20.86; Ptrend = 0.04) cHL risk. Other dietary patterns were not clearly associated with cHL. We report the first evidence for a role of dietary pattern in cHL etiology. Diets featuring high intake of meat or desserts and sweets may increase cHL risk. PMID:26182945

Dietary pattern and risk of hodgkin lymphoma in a population-based case-control study.

PubMed

Epstein, Mara M; Chang, Ellen T; Zhang, Yawei; Fung, Teresa T; Batista, Julie L; Ambinder, Richard F; Zheng, Tongzhang; Mueller, Nancy E; Birmann, Brenda M

2015-09-01

Classic Hodgkin lymphoma (cHL) has few known modifiable risk factors, and the relationship between diet and cHL risk is unclear. We performed the first investigation of an association between dietary pattern and cHL risk in 435 cHL cases and 563 population-based controls from Massachusetts and Connecticut (1997-2000) who completed baseline diet questionnaires. We identified 4 major dietary patterns ("vegetable," "high meat," "fruit/low-fat dairy," "desserts/sweets") using principal components analysis. We computed multivariable odds ratios and 95% confidence intervals for associations of dietary pattern score (quartiles) with younger-adult (age <50 years), older-adult (age ≥50 years), and overall cHL risk. Secondary analyses examined associations by histological subtype and tumor Epstein-Barr virus (EBV) status. A diet high in desserts/sweets was associated with younger-adult (odds ratio(quartile 4 vs. quartile 1) = 1.60, 95% confidence interval: 1.05, 2.45; Ptrend = 0.008) and EBV-negative, younger-adult (odds ratio = 2.11, 95% confidence interval: 1.31, 3.41; Ptrend = 0.007) cHL risk. A high meat diet was associated with older-adult (odds ratio = 3.34, 95% confidence interval: 1.02, 10.91; Ptrend = 0.04) and EBV-negative, older-adult (odds ratio = 4.64, 95% confidence interval: 1.03, 20.86; Ptrend = 0.04) cHL risk. Other dietary patterns were not clearly associated with cHL. We report the first evidence for a role of dietary pattern in cHL etiology. Diets featuring high intake of meat or desserts and sweets may increase cHL risk. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Complexation of uranium(VI) with glutarimidoxioxime: thermodynamic and computational studies.

PubMed

Endrizzi, Francesco; Melchior, Andrea; Tolazzi, Marilena; Rao, Linfeng

2015-08-21

The complex formation between a cyclic ligand glutarimidoxioxime (denoted as HL(III) in this paper) and UO2(2+) is studied by potentiometry and microcalorimetry. Glutarimidoxioxime (HL(III)), together with glutarimidedioxime (H2L(I)) and glutardiamidoxime (H2L(II)), belongs to a family of amidoxime derivatives with prospective applications as binding agents for the recovery of uranium from seawater. An optimized procedure of synthesis that leads to the preparation of glutarimidoxioxime in the absence of other amidoxime byproducts is described in this paper. Speciation models based on the thermodynamic results from this study indicate that, compared with H2L(I) and H2L(II), HL(III) forms a much weaker complex with UO2(2+), UO2(L(III))(+), and cannot effectively compete with the hydrolysis equilibria of UO2(2+) under neutral or alkaline conditions. DFT computations, taking into account the solvation by including discrete hydration water molecules and bulk solvent effects, were performed to evaluate the structures and energies of the possible isomers of UO2(L(III))(+). Differing from the tridentate or η(2)-coordination modes previously found in the U(vi) complexes with amidoxime-related ligands, a bidentate mode, involving the oxygen of the oxime group and the nitrogen of the imino group, is found to be the most probable mode in UO2(L(III))(+). The bidentate coordination mode seems to be stabilized by the formation of a hydrogen bond between the carbonyl group of HL(III) and a water molecule in the hydration sphere of UO2(2+).

LMP1 and Dynamic Progressive Telomere Dysfunction: A Major Culprit in EBV-Associated Hodgkin's Lymphoma.

PubMed

Knecht, Hans; Mai, Sabine

2017-06-27

Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is expressed in germinal-center-derived, mononuclear Hodgkin (H) and multinuclear, diagnostic Reed-Sternberg (RS) cells in classical EBV-positive Hodgkin's lymphoma (cHL). LMP1 expression in EBV-negative H-cell lines results in a significantly increased number of RS cells. In a conditional, germinal-center-derived B-cell in vitro system, LMP1 reversibly down-regulates the shelterin proteins, telomeric repeat binding factor (TRF)1, TRF2, and protection of telomeres (POT)1. This down-regulation is associated with progressive 3D shelterin disruption, resulting in telomere dysfunction, progression of complex chromosomal rearrangements, and multinuclearity. TRF2 appears to be the key player. Thus, we hypothesize that the 3D interaction of telomeres and TRF2 is disrupted in H cells, and directly associated with the formation of H and RS cells. Using quantitative 3D co-immuno-TRF2-telomere fluorescent in situ hybridization (3D TRF2/Telo-Q-FISH) applied to monolayers of primary H and RS cells, we demonstrate TRF2-telomere dysfunction in EBV-positive cHL. However, in EBV-negative cHL a second molecular mechanism characterized by massive up-regulation of TRF2, but attrition of telomere signals, is also identified. These facts point towards a shelterin-related pathogenesis of cHL, where two molecularly disparate mechanisms converge at the level of 3D Telomere-TRF2 interactions, leading to the formation of RS cells.

Implementing a DICOM-HL7 interface application

NASA Astrophysics Data System (ADS)

Fritz, Steven L.; Munjal, Sunita; Connors, James; Csipo, Deszu

1995-05-01

The DICOM standard, in addition to resolving certain problems with the ACR-NEMA 2.0 standard regarding network support and the clinical data dictionary, added new capabilities, in the form of study content notification and patient, study and results management services, intended to assist in interfacing between PACS and HIS or RIS systems. We have defined and implemented a mechanism that allows a DICOM application entity (AE) to interrogate an HL7 based RIS using DICOM services. The implementation involved development of a DICOM- HL7 gateway which converted between DICOM and HL7 messages to achieve the desired retrieval capability. This mechanism, based on the DICOM query/retrieve service, was used to interface a DeJarnette Research film digitizer to an IDXrad RIS at the University of Maryland Medical Systems hospital in Baltimore, Maryland. A C++ class library was developed for both DICOM and HL7 massaging, with several constructors used to convert between the two standards.

Development of an HL7 interface engine, based on tree structure and streaming algorithm, for large-size messages which include image data.

PubMed

Um, Ki Sung; Kwak, Yun Sik; Cho, Hune; Kim, Il Kon

2005-11-01

A basic assumption of Health Level Seven (HL7) protocol is 'No limitation of message length'. However, most existing commercial HL7 interface engines do limit message length because they use the string array method, which is run in the main memory for the HL7 message parsing process. Specifically, messages with image and multi-media data create a long string array and thus cause the computer system to raise critical and fatal problem. Consequently, HL7 messages cannot handle the image and multi-media data necessary in modern medical records. This study aims to solve this problem with the 'streaming algorithm' method. This new method for HL7 message parsing applies the character-stream object which process character by character between the main memory and hard disk device with the consequence that the processing load on main memory could be alleviated. The main functions of this new engine are generating, parsing, validating, browsing, sending, and receiving HL7 messages. Also, the engine can parse and generate XML-formatted HL7 messages. This new HL7 engine successfully exchanged HL7 messages with 10 megabyte size images and discharge summary information between two university hospitals.

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

Takahashi, Sanemichi Z.; Inutsuka, Shu-ichiro, E-mail: sanemichi@astr.tohoku.ac.jp, E-mail: inutsuka@nagoya-u.jp

Recent ALMA observation has revealed multiple ring structures formed in a protoplanetary disk around HL Tau. Prior to the ALMA observation of HL Tau, theoretical analysis of secular gravitational instability (GI) described a possible formation of multiple ring structures with separations of 13 au around a radius of 100 au in protoplanetary disks under certain conditions. In this article, we reanalyze the viability of secular GI by adopting the physical values inferred from the observations. We derive the radial distributions of the most unstable wavelength and the growth timescale of secular GI and verify that secular GI can form themore » ring structures observed in HL Tau. When a turbulent viscosity coefficient α remains small in the inner region of the disk, secular GI grows in the whole disk. Thus, the formation of planetary mass objects should occur first in the inner region as a result of gravitational fragmentation after the nonlinear growth of secular GI. In this case, the resulting objects are expected to create gaps at r  ∼ 10 au and ∼30 au. As a result, all ring structures in HL Tau can be created by secular GI. If this scenario is realized in HL Tau, the outer region corresponds to the earlier growth phase of the most unstable mode of secular GI, and the inner region corresponds to the outcome of the nonlinear growth of secular GI. Therefore, this interpretation suggests that we are possibly witnessing both the beginning and the end of planet formation in HL Tau.« less

NLS-RARα promotes proliferation and inhibits differentiation in HL-60 cells.

PubMed

Hu, Xiu-Xiu; Zhong, Liang; Zhang, Xi; Gao, Yuan-Mei; Liu, Bei-Zhong

2014-01-01

A unique mRNA produced in leukemic cells from a t(15;17) acute promyelocytic leukemia (APL) patient encodes a fusion protein between the retinoic acid receptor α (RARα) and a myeloid gene product called PML. Studies have reported that neutrophil elastase (NE) cleaves bcr-1-derived PML-RARα in early myeloid cells, leaving only the nuclear localization signal (NLS) of PML attached to RARα. The resultant NLS-RARα fusion protein mainly localizes to, and functions within, the cell nucleus. It is speculated that NLS-RARα may act in different ways from the wild-type RARα, but its biological characteristics have not been reported. This study takes two approaches. Firstly, the NLS-RARα was silenced with pNLS-RARα-shRNA. The mRNA and protein expression of NLS-RARα were detected by RT-PCR and Western blot respectively. Cell proliferation in vitro was assessed by MTT assay. Flow cytometry (FCM) was used to detect the differentiation of cells. Secondly, the NLS-RARα was over-expressed by preparation of recombinant adenovirus HL-60/pAd-NLS-RARα. The assays of mRNA and protein expression of NLS-RARα, and cell proliferation, were as above. By contrast, cell differentiation was stimulated by all trans retinoic acid (ATRA) (2.5µmol/L) at 24h after virus infection of pAd-NLS-RARα, and then detected by CD11b labeling two days later. The transcription and translation of C-MYC was detected in HL-60/pAd-NLS-RARα cells which treated by ATRA. Our results showed that compared to the control groups, the expression of NLS-RARα was significantly reduced in the HL-60/pNLS-RARα-shRNA cells, and increased dramatically in the HL-60/pAd-NLS-RARα cells. The proliferation was remarkably inhibited in the HL-60/pNLS-RARα-shRNA cells in a time-dependent manner, but markedly promoted in the HL-60/pAd-NLS-RARα cells. FCM outcome revealed the differentiation increased in HL-60/pNLS-RARα-shRNA cells, and decreased in the HL-60/pAd-NLS-RARα cells treated with 2.5µmol/L ATRA. The expression of C-MYC increased strikingly in HL-60/pAd-NLS-RARα cells treated with 2.5µmol/L ATRA. Down-regulation of NLS-RARα expression inhibited the proliferation and induced the differentiation of HL-60 cells. On the contrary, over-expression of NLS-RARα promoted proliferation and reduced the ATRA-induced differentiation of HL-60 cells.

The importance and impact of patients' health literacy on low back pain management: a systematic review of literature.

PubMed

Edward, Jean; Carreon, Leah Yacat; Williams, Mark V; Glassman, Steven; Li, Jing

2018-02-01

Health literacy (HL) and the overall ability of patients to seek, understand, and apply health information play an important role in the management of chronic pain conditions. Awareness of how patients' HL skills influence their pain experience and how their ability to understand the treatment regimen and to manage chronic pain may allow physicians to adjust clinical treatment accordingly. Despite the prevalence and the substantial economic impact of chronic low back pain (LBP), little is known about the relationship between HL and the treatment and management of this common disease entity. The purpose of this systematic review of published research was to examine the importance and the implications of HL in the treatment and management of LBP. A literature search was performed in Web of Science, PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsychInfo using medical subject heading (MeSH) terms related to LBP, HL, and patient education, which yielded only three studies that directly addressed HL among patients suffering from LBP. We identified only a limited number of studies that focused specifically on HL in the LBP population that were included in this review. The majority of studies excluded from this review focused on patient levels of educational attainment and patient education programs without addressing patients' HL levels and their impact on adherence to educational programs, self-care management, and rehabilitation, among other factors. The three studies that are critically reviewed in this review either use a direct measure of HL or make an effort to address HL in their programs. All three studies emphasize the importance of considering the HL of patients in the treatment and management of LBP. Building on these studies and the narrative review of other relevant literature, we identified significant gaps in current research addressing HL in the treatment and management of LBP. We developed recommendations for future research based on an assessment of strengths and limitations of available evidence-based studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Two isomorphous Co(ii) coordination polymers based on new α,α-disubstituted derivatives of zoledronic acid: synthesis, structures and properties.

PubMed

Rojek, Tomasz; Goldeman, Waldemar; Slepokura, Katarzyna; Duczmal, Marek; Wojciechowska, Agnieszka; Matczak-Jon, Ewa

2017-05-30

Two novel α,α-disubstituted derivatives of zoledronic acid, namely 1-hydroxy-2-(1H-imidazol-1-yl)-2-methylpropylidene-1,1-diphosphonic acid (H 4 L1) and 1-hydroxy-2-[1-(1H-imidazol-1-yl)cyclopropyl]ethylidene-1,1-diphosphonic acid (H 4 L2) were synthesized and structurally characterized by single-crystal X-ray diffraction. The reaction of cobalt acetate with H 4 L1 and H 4 L2 carried out under hydrothermal conditions afforded two isomorphous Co 3 (HL1) 2 (H 2 O) 6 ·6H 2 O (1a) and Co 3 (HL2) 2 (H 2 O) 6 ·6H 2 O (2a) complexes. Both compounds are characterized by means of X-ray crystallography, IR and NIR-Vis-UV spectroscopic methods. Furthermore, their magnetic properties and thermal stabilities are reported. The crystals of 1a and 2a feature infinite 1D polymeric chains built from alternately arranged dinuclear [Co2(HL1/HL2)(H 2 O) 2 ] 2 units and {Co1O 6 } octahedra running along the [1[combining macron]10] crystallographic direction. In both compounds, crystallographically distinct Co1 and Co2 atoms are six-coordinated. As is reflected in T values (T - index of tetragonality), the coordination environment of Co1 generates a slightly elongated octahedron (T = 0.94), whereas a slightly compressed octahedron (T = 1.06 for 1a and 1.05 for 2a) is formed around Co2. An assumption that the d-d type absorption is mainly attributed to the inversion related Co2 centers, whose population is two times higher than that of Co1, afforded a good correlation between calculated transition energies and experimental NIR-Vis-UV spectra. The magnetic susceptibility measurements analyzed in terms of a spin-3/2 Heisenberg trimer chain revealed that Co1Co2 interactions within the trimer are antiferromagnetic whereas Co2Co2 intertrimer interactions are ferromagnetic.

Studies on the apoptotic activity of natural and synthetic retinoids: discovery of a new class of synthetic terphenyls that potently support cell growth and inhibit apoptosis in neuronal and HL-60 cells.

PubMed

Simoni, Daniele; Giannini, Giuseppe; Roberti, Marinella; Rondanin, Riccardo; Baruchello, Riccardo; Rossi, Marcello; Grisolia, Giuseppina; Invidiata, Francesco Paolo; Aiello, Stefania; Marino, Silvia; Cavallini, Sabrina; Siniscalchi, Anna; Gebbia, Nicola; Crosta, Lucia; Grimaudo, Stefania; Abbadessa, Vincenzo; Di Cristina, Antonietta; Tolomeo, Manlio

2005-06-30

New terphenyl derivatives have been synthesized and tested for their effect on cell survival in serum-free cultures. These compounds protected HL60 cells from death and supported their growth with an activity higher than that of the natural 14-hydroxy-retro-retinol. Terphenyls 26 and 28 also possess antiapoptotic activity on neuronal cells, proving them as possible candidates for the treatment of neurodegenerative and ischemic diseases.

Characterization of plasma current quench during disruptions at HL-2A

NASA Astrophysics Data System (ADS)

Zhu, Jinxia; Zhang, Yipo; Dong, Yunbo; HL-2A Team

2017-05-01

The most essential assumptions of physics for the evaluation of electromagnetic forces on the plasma-facing components due to a disruption-induced eddy current are characteristics of plasma current quenches including the current quench rate or its waveforms. The characteristics of plasma current quenches at HL-2A have been analyzed during spontaneous disruptions. Both linear decay and exponential decay are found in the disruptions with the fastest current quenches. However, there are two stages of current quench in the slow current quench case. The first stage with an exponential decay and the second stage followed by a rapid linear decay. The faster current quench rate corresponds to the faster movement of plasma displacement. The parameter regimes on the current quench time and the current quench rates have been obtained from disruption statistics at HL-2A. There exists no remarkable difference for distributions obtained between the limiter and the divertor configuration. This data from HL-2A provides basic data of the derivation of design criteria for a large-sized machine during the current decay phase of the disruptions.

Three Korean Heritage Language Teachers' Identities, Their Identification of Their Students, and Their Instructional Practices

ERIC Educational Resources Information Center

Kim, Jung-In; Kim, Miseon

2016-01-01

This study examined the instructional focuses and practices of three Korean heritage language (HL) teachers in community-based HL schools related not only to their constructed identities as HL teachers, but also to their students. Constant-comparative analyses of interviews and classroom observations across the three teacher cases showed that each…

Integrating Genomic Resources with Electronic Health Records using the HL7 Infobutton Standard

PubMed Central

Overby, Casey Lynnette; Del Fiol, Guilherme; Rubinstein, Wendy S.; Maglott, Donna R.; Nelson, Tristan H.; Milosavljevic, Aleksandar; Martin, Christa L.; Goehringer, Scott R.; Freimuth, Robert R.; Williams, Marc S.

2016-01-01

Summary Background The Clinical Genome Resource (ClinGen) Electronic Health Record (EHR) Workgroup aims to integrate ClinGen resources with EHRs. A promising option to enable this integration is through the Health Level Seven (HL7) Infobutton Standard. EHR systems that are certified according to the US Meaningful Use program provide HL7-compliant infobutton capabilities, which can be leveraged to support clinical decision-making in genomics. Objectives To integrate genomic knowledge resources using the HL7 infobutton standard. Two tactics to achieve this objective were: (1) creating an HL7-compliant search interface for ClinGen, and (2) proposing guidance for genomic resources on achieving HL7 Infobutton standard accessibility and compliance. Methods We built a search interface utilizing OpenInfobutton, an open source reference implementation of the HL7 Infobutton standard. ClinGen resources were assessed for readiness towards HL7 compliance. Finally, based upon our experiences we provide recommendations for publishers seeking to achieve HL7 compliance. Results Eight genomic resources and two sub-resources were integrated with the ClinGen search engine via OpenInfobutton and the HL7 infobutton standard. Resources we assessed have varying levels of readiness towards HL7-compliance. Furthermore, we found that adoption of standard terminologies used by EHR systems is the main gap to achieve compliance. Conclusion Genomic resources can be integrated with EHR systems via the HL7 Infobutton standard using OpenInfobutton. Full compliance of genomic resources with the Infobutton standard would further enhance interoperability with EHR systems. PMID:27579472

Low-Dose Chest Computed Tomography for Lung Cancer Screening Among Hodgkin Lymphoma Survivors: A Cost-Effectiveness Analysis

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

Wattson, Daniel A., E-mail: dwattson@partners.org; Hunink, M.G. Myriam; DiPiro, Pamela J.

2014-10-01

Purpose: Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Methods and Materials: Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs.more » LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Results: Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. Conclusions: HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening may be cost effective for all smokers but possibly not for nonsmokers despite a small life expectancy benefit.« less

Purpurogemutantin and Purpurogemutantidin, New Drimenyl Cyclohexenone Derivatives Produced by a Mutant Obtained by Diethyl Sulfate Mutagenesis of a Marine-Derived Penicillium purpurogenum G59

PubMed Central

Fang, Shi-Ming; Cui, Cheng-Bin; Li, Chang-Wei; Wu, Chang-Jing; Zhang, Zhi-Jun; Li, Li; Huang, Xiao-Jun; Ye, Wen-Cai

2012-01-01

Two new drimenyl cyclohexenone derivatives, named purpurogemutantin (1) and purpurogemutantidin (2), and the known macrophorin A (3) were isolated from a bioactive mutant BD-1-6 obtained by random diethyl sulfate (DES) mutagenesis of a marine-derived Penicillium purpurogenum G59. Structures and absolute configurations of 1 and 2 were determined by extensive spectroscopic methods, especially 2D NMR and electronic circular dichroism (ECD) analysis. Possible biosynthetic pathways for 1–3 were also proposed and discussed. Compounds 1 and 2 significantly inhibited human cancer K562, HL-60, HeLa, BGC-823 and MCF-7 cells, and compound 3 also inhibited the K562 and HL-60 cells. Both bioassay and chemical analysis (HPLC, LC-ESIMS) demonstrated that the parent strain G59 did not produce 1–3, and that DES-induced mutation(s) in the mutant BD-1-6 activated some silent biosynthetic pathways in the parent strain G59, including one set for 1–3 production. PMID:22822371

A case study: planning a statewide information resource for health professionals: an evidence-based approach.

PubMed

Aspinall, Erinn E; Chew, Katherine; Watson, Linda; Parker, Mary

2009-10-01

What is the best approach for implementing a statewide electronic health library (eHL) to serve all health professionals in Minnesota? The research took place at the University of Minnesota Health Sciences Libraries. In January 2008, the authors began planning a statewide eHL for health professionals following the five-step process for evidence-based librarianship: formulating the question, finding the best evidence, appraising the evidence, assessing costs and benefits, and evaluating the effectiveness of resulting actions. The authors identified best practices for developing a statewide eHL for health professionals relating to audience or population served, information resources, technology and access, funding model, and implementation and sustainability. They were compared to the mission of the eHL project to drive strategic directions by developing recommendations. EBL can guide the planning process for a statewide eHL, but findings must be tailored to the local environment to address information needs and ensure long-term sustainability.

A case study: planning a statewide information resource for health professionals: an evidence-based approach

PubMed Central

Chew, Katherine; Watson, Linda; Parker, Mary

2009-01-01

Question: What is the best approach for implementing a statewide electronic health library (eHL) to serve all health professionals in Minnesota? Setting: The research took place at the University of Minnesota Health Sciences Libraries. Methods: In January 2008, the authors began planning a statewide eHL for health professionals following the five-step process for evidence-based librarianship: formulating the question, finding the best evidence, appraising the evidence, assessing costs and benefits, and evaluating the effectiveness of resulting actions. Main Results: The authors identified best practices for developing a statewide eHL for health professionals relating to audience or population served, information resources, technology and access, funding model, and implementation and sustainability. They were compared to the mission of the eHL project to drive strategic directions by developing recommendations. Conclusion: EBL can guide the planning process for a statewide eHL, but findings must be tailored to the local environment to address information needs and ensure long-term sustainability. PMID:19851487

Hierarchical Recognition Scheme for Human Facial Expression Recognition Systems

PubMed Central

Siddiqi, Muhammad Hameed; Lee, Sungyoung; Lee, Young-Koo; Khan, Adil Mehmood; Truc, Phan Tran Ho

2013-01-01

Over the last decade, human facial expressions recognition (FER) has emerged as an important research area. Several factors make FER a challenging research problem. These include varying light conditions in training and test images; need for automatic and accurate face detection before feature extraction; and high similarity among different expressions that makes it difficult to distinguish these expressions with a high accuracy. This work implements a hierarchical linear discriminant analysis-based facial expressions recognition (HL-FER) system to tackle these problems. Unlike the previous systems, the HL-FER uses a pre-processing step to eliminate light effects, incorporates a new automatic face detection scheme, employs methods to extract both global and local features, and utilizes a HL-FER to overcome the problem of high similarity among different expressions. Unlike most of the previous works that were evaluated using a single dataset, the performance of the HL-FER is assessed using three publicly available datasets under three different experimental settings: n-fold cross validation based on subjects for each dataset separately; n-fold cross validation rule based on datasets; and, finally, a last set of experiments to assess the effectiveness of each module of the HL-FER separately. Weighted average recognition accuracy of 98.7% across three different datasets, using three classifiers, indicates the success of employing the HL-FER for human FER. PMID:24316568

Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma.

PubMed

Liu, W Robert; Shipp, Margaret A

2017-11-23

Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number-dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor-positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade. © 2017 by The American Society of Hematology.

An injury mortality prediction based on the anatomic injury scale

PubMed Central

Wang, Muding; Wu, Dan; Qiu, Wusi; Wang, Weimi; Zeng, Yunji; Shen, Yi

2017-01-01

Abstract To determine whether the injury mortality prediction (IMP) statistically outperforms the trauma mortality prediction model (TMPM) as a predictor of mortality. The TMPM is currently the best trauma score method, which is based on the anatomic injury. Its ability of mortality prediction is superior to the injury severity score (ISS) and to the new injury severity score (NISS). However, despite its statistical significance, the predictive power of TMPM needs to be further improved. Retrospective cohort study is based on the data of 1,148,359 injured patients in the National Trauma Data Bank hospitalized from 2010 to 2011. Sixty percent of the data was used to derive an empiric measure of severity of different Abbreviated Injury Scale predot codes by taking the weighted average death probabilities of trauma patients. Twenty percent of the data was used to create computing method of the IMP model. The remaining 20% of the data was used to evaluate the statistical performance of IMP and then be compared with the TMPM and the single worst injury by examining area under the receiver operating characteristic curve (ROC), the Hosmer–Lemeshow (HL) statistic, and the Akaike information criterion. IMP exhibits significantly both better discrimination (ROC-IMP, 0.903 [0.899–0.907] and ROC-TMPM, 0.890 [0.886–0.895]) and calibration (HL-IMP, 9.9 [4.4–14.7] and HL-TMPM, 197 [143–248]) compared with TMPM. All models show slight changes after the extension of age, gender, and mechanism of injury, but the extended IMP still dominated TMPM in every performance. The IMP has slight improvement in discrimination and calibration compared with the TMPM and can accurately predict mortality. Therefore, we consider it as a new feasible scoring method in trauma research. PMID:28858124

Syntheses and structure characterization of ten acid-base hybrid crystals based on N-containing aromatic brønsted bases and mineral acids

NASA Astrophysics Data System (ADS)

Lin, Zhihao; Jin, Shouwen; Li, Xiaoliang; Xiao, Xiao; Hu, Kaikai; Guo, Ming; Chi, Xinchen; Liu, Hui; Wang, Daqi

2017-10-01

Cocrystallization of the aromatic brønsted bases with a series of mineral acids gave a total of ten hybrid salts with the compositions: (2-methylquinoline)2: (hydrochloride acid): 3H2O [(HL1)+. (L1)·· (Cl-) · (H2O)3] (1), (6-bromobenzo[d]thiazol-2-amine): (hydrochloride acid) [(HL2)+. (Cl-)] (2), (6-bromobenzo[d]thiazol-2-amine): (nitric acid) [(HL2)+. (NO3-)] (3), (6-bromobenzo[d]thiazol-2-amine): (sulfuric acid) [(HL2)+ · (HSO4)-] (4), (6-bromobenzo[d]thiazol-2-amine): (phosphoric acid) [(HL2)+ · (H2PO4)-] (5), (5,7-dimethyl-1,8-naphthyridine-2-amine): (hydrochloride acid): 3H2O [(HL3)+ · (Cl-) (H2O)3] (6), (5,7-dimethyl-1,8-naphthyridine-2-amine): (hydrobromic acid): CH3OH [(HL3)+ · (Br)- · CH3OH] (7), (5,7-dimethyl-1,8-naphthyridine-2-amine): (sulfuric acid): H2O [(HL3)+ · (HSO4)- · H2O] (8), (2-aminophenol): (phosphoric acid) [(HL4)+ · (H2PO4)-] (9), and (2-amino-4-chlorophenol): (phosphoric acid) [(HL5)+ · (H2PO4)-] (10). The ten salts have been characterized by X-ray diffraction analysis, IR, and elemental analysis, and the melting points of all the salts were also reported. And their structural and supramolecular aspects are fully analyzed. The result reveals that among the ten investigated crystals the ring N of the heterocycle or the NH2 in the aminophenol are protonated when the acids are deprotonated, and the crystal packing is interpreted in terms of the strong charge-assisted classical hydrogen bonds between the NH+/NH3+ and deprotonated acidic groups. Further analysis of the crystal packing of the salts indicated that a different family of additional CHsbnd O, CHsbnd Cl, CH3sbnd N, CH3sbnd O, CHsbnd Br, CH3sbnd Br, Brsbnd Cl, Clsbnd S, Osbnd S, Osbnd O, Brsbnd S, Hsbnd H, and π-π associations contribute to the stabilization and expansion of the total high-dimensional frameworks. For the coexistence of the various weak nonbonding interactions these structures adopted homo or hetero supramolecular synthons or both. Some classical supramolecular synthons, such as R22(8), R42(8), R43(10) and R44(12), usually observed in the organic solids, were again shown to be involved in constructing most of these H-bonding networks.

Thiourea derivatives as chelating agents for bioconjugation of rhenium and technetium.

PubMed

Gomez, J D Castillo; Hagenbach, A; Gerling-Driessen, U I M; Koksch, B; Beindorff, N; Brenner, W; Abram, U

2017-10-31

Potential tetradentate thiocarbamoylbenzamidine derivatives H 4 L have been synthesized from the corresponding benzimidoyl chlorides and triglycine. They are suitable chelating agents for the oxidotechnetium(v) and oxidorhenium(v) cores and form stable, neutral [MO(HL)] complexes with an equatorial SN 3 coordination sphere and an additional, uncoordinated carboxylic group, which can be used for bioconjugation. Representatives of the rhenium and 99 Tc products have been isolated and analyzed with spectroscopic methods and X-ray diffraction. Bioconjugates of these complexes with angiotensin-II have been synthesized and structurally characterized. Analogous 99m Tc complexes have been produced and tested in vitro and in vivo. The experiments confirm a considerable stability for the [ 99m Tc(HL)] product as well as for its bioconjugate and recommend this class of compounds for further bioconjugation studies towards clinical applications.

Synthesis and characterization of two dehydroacetic acid derivatives and molybdenum(V) complexes: an NMR and crystallographic study

NASA Astrophysics Data System (ADS)

Cindrić, Marina; Vrdoljak, Višnja; Kajfež Novak, Tanja; Ćurić, Manda; Brbot-Šaranović, Ana; Kamenar, Boris

2004-09-01

Two enaminones ethyl 4-(4-hydroxy-6-methyl-2 H-pyran-2-on-3-yl)-2-(tryptamino)-4-oxo-2-butenoate ( HL1) and 3-(1-tryptaminoetylidene)-6-methyl-2 H-pyran-2,4(3H)-dione ( HL2) have been prepared by the reactions of tryptamine with 2-hydroxy-4-(4-hydroxy)-6-methyl)-2 Hbb-pyrane-2-on-3-yl)-4-oxo-2-butenoate (ehmpb) or with dehydroacetic acid (dha). The NMR spectroscopy confirmed that both tautomeric forms of HL1: endo-enol (tautomer A with hydroxyl group at position 4) and exo-enol form (tautomer B with hydroxyl group at position 7) are present in the DMSO- d6 solution. The molecular and crystal structure as well as the NMR data of HL2 showed that the condensation of dha and tryptamine occurs at acetyl-carbonyl and not at the pyrone-carbonyl group. Also new dinuclear [Mo 2O 4(L 1) 2(CH 3OH) 2] ( 1) and hexanuclear molybdenum(V) complexes (C 10H 12NH)[Mo 6O 12(OCH 3) 4(acac) 3] ( 2) have been prepared by the reactions of [Mo 2O 3(acac) 4] (acac=acetilacetonate ion) with HL1 or with tryptamine. All compounds have been characterized also by means of elemental analyses, IR spectroscopy as well as by thermal analyses.

Spectroscopic, structural, electrochemical and computational studies of some new 2-thienyl-containing β-diketonate complexes of cobalt(II), nickel(II) and copper(II)

NASA Astrophysics Data System (ADS)

Ahumada, Guillermo; Fuentealba, Mauricio; Roisnel, Thierry; Kahlal, Samia; Córdova, Ricardo; Carrillo, David; Saillard, Jean-Yves; Hamon, Jean-René; Manzur, Carolina

2017-12-01

In this work, we present the synthesis of the unsymmetrical β-diketone 1-(2-thienyl)-3-(4-fluorophenyl)-propane-1,3-dione (HL) and its corresponding Co(II), Ni(II) and Cu(II) bis(β-diketonato) complexes 1-3, respectively. The four new compounds were isolated in good yields (65-70%), and characterized by mass spectrometry, elemental analysis, FT-IR and UV-Vis spectroscopy and, in the case of HL, by 1H, 13C and 19F NMR spectroscopy. In addition, the molecular identities and the geometries of the β-diketone HL and complex 3 were confirmed by X-ray diffraction analysis. The dicarbonyl derivative HL does exist as the diketo tautomeric form in DMSO solution and as its keto-enol tautomer in the solid-state with the sbnd OH group adjacent to the 4-fluorophenyl unit. The keto-enol isomer was computed to be more stable by 8.2 kcal/mol in free energy at room temperature. In 3, the Cu(II) center adopts a perfect square-planar geometry. Two reduction processes were observed in the cyclovoltammogram of 3 at -1.30 and -1.80 V vs. Fc/Fc+, with copper deposit on the surface of the electrode. DFT and TD-DFT calculations on HL and complex 3 allow rationalizing their stability, bonding and properties.

Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

PubMed

Moccia, Alden A; Hitz, Felicitas; Hoskins, Paul; Klasa, Richard; Power, Maryse M; Savage, Kerry J; Shenkier, Tamara; Shepherd, John D; Slack, Graham W; Song, Kevin W; Gascoyne, Randy D; Connors, Joseph M; Sehn, Laurie H

2017-02-01

The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

Experiements with an inactivated hepatitis leptospirosis vaccine in vaccination programmes for dogs.

PubMed

Wilson, J H; Hermann-Dekkers, W M; Leemans-Dessy, S; Meijer, J W

1977-06-25

A fluid adjuvanted vaccine consisting of inactivated hepatitis virus (iH) and leptospirae antigens (L) was developed. The vaccine (Kavak iHL; Duphar) was tested in several vaccination programmes both alone and in combination with freeze dried measles (M) or distemper (D) vaccines. The results demonstrate that this new vaccine is also effective in pups with maternally derived antibodies, although a second vaccination at 14 weeks of age is recommended to boost the first vaccination. For the booster vaccination either the iHL-vaccine or the liver attenuated hepatitis vaccine (H) can be used.

Antibody titers against EBNA1 and EBNA2 in relation to Hodgkin lymphoma and history of infectious mononucleosis

PubMed Central

Mueller, Nancy E.; Lennette, Evelyne T.; Dupnik, Kathryn; Birmann, Brenda M.

2013-01-01

A role for Epstein Barr virus (EBV) in Hodgkin lymphoma (HL) pathogenesis is supported by the detection of EBV genome in about one-third of HL cases, but is not well defined. We previously reported that an elevated pre-diagnosis antibody titer against EBV nuclear antigens (EBNA) was the strongest serologic predictor of subsequent HL. For the present analysis, we measured antibody levels against EBNA components EBNA1 and EBNA2 and computed their titer ratio (anti-EBNA1:2) in serum samples from HL cases and healthy siblings. We undertook this analysis to examine whether titer patterns atypical of well-resolved EBV infection, such as an anti-EBNA1:2 ratio ≤1.0, simply reflect history of infectious mononucleosis (IM), an HL risk factor, or independently predict HL risk. Participants were selected from a previous population-based case-control study according to their history of IM. We identified 55 EBV-seropositive persons with a history of IM (IM+; 33 HL cases, 22 siblings) and frequency-matched a comparison series of 173 IM history-negative, EBV-seropositive subjects on HL status, gender, age, and year of blood draw (IM−; 105 cases, 58 siblings). In multivariate logistic regression models, an anti-EBNA1:2 ratio ≤1.0 was significantly more prevalent in HL cases than siblings (odds ratio, 95% confidence interval=2.43, 1.05–5.65); similar associations were apparent within the IM+ and IM− groups. EBNA antibodies were not significantly associated with IM history in HL cases or siblings. These associations suggest that chronic or more severe EBV infection is a risk factor for HL, independent of IM history. PMID:21805472

Disparities in survival after Hodgkin lymphoma: a population-based study

PubMed Central

Keegan, Theresa H.M.; Clarke, Christina A.; Chang, Ellen T.; Shema, Sarah J.; Glaser, Sally L.

2009-01-01

Survival after Hodgkin lymphoma (HL) is generally favorable, but may vary by patient demographic characteristics. The authors examined HL survival according to race/ethnicity and neighborhood socioeconomic status (SES), determined from residential census block group at diagnosis. For 12,492 classical HL patients ≥15 years diagnosed in California during 1988-2006 and followed through 2007, we determined risk of overall and HL-specific death using Cox proportional hazards regression; analyses were stratified by age and Ann Arbor stage. Irrespective of disease stage, patients with lower neighborhood SES had worse overall and HL-specific survival than patients with higher SES. Patients with the lowest quintile of neighborhood SES had a 64% (patients aged 15-44 years) and 36% (≥45 years) increased risk of HL-death compared to patients with the highest quintile of SES; SES results were similar for overall survival. Even after adjustment for neighborhood SES, blacks and Hispanics had increased risks of HL-death 74% and 43% (15-44 years) and 40% and 17% (≥45 years), respectively, higher than white patients. The racial/ethnic differences in survival were evident for all stages of disease. These data provide evidence for substantial, and probably remediable, racial/ethnic and neighborhood SES disparities in HL outcomes. PMID:19557531

Retinoic Acid Therapy Resistance Progresses from Unilineage to Bilineage in HL-60 Leukemic Blasts

PubMed Central

Jensen, Holly A.; Bunaciu, Rodica P.; Ibabao, Christopher N.; Myers, Rebecca; Varner, Jeffrey D.; Yen, Andrew

2014-01-01

Emergent resistance can be progressive and driven by global signaling aberrations. All-trans retinoic acid (RA) is the standard therapeutic agent for acute promyelocytic leukemia, but 10–20% of patients are not responsive, and initially responsive patients relapse and develop retinoic acid resistance. The patient-derived, lineage-bipotent acute myeloblastic leukemia (FAB M2) HL-60 cell line is a potent tool for characterizing differentiation-induction therapy responsiveness and resistance in t(15;17)-negative cells. Wild-type (WT) HL-60 cells undergo RA-induced granulocytic differentiation, or monocytic differentiation in response to 1,25-dihydroxyvitamin D3 (D3). Two sequentially emergent RA-resistant HL-60 cell lines, R38+ and R38-, distinguishable by RA-inducible CD38 expression, do not arrest in G1/G0 and fail to upregulate CD11b and the myeloid-associated signaling factors Vav1, c-Cbl, Lyn, Fgr, and c-Raf after RA treatment. Here, we show that the R38+ and R38- HL-60 cell lines display a progressive reduced response to D3-induced differentiation therapy. Exploiting the biphasic dynamic of induced HL-60 differentiation, we examined if resistance-related defects occurred during the first 24 h (the early or “precommitment” phase) or subsequently (the late or “lineage-commitment” phase). HL-60 were treated with RA or D3 for 24 h, washed and retreated with either the same, different, or no differentiation agent. Using flow cytometry, D3 was able to induce CD38, CD11b and CD14 expression, and G1/G0 arrest when present during the lineage-commitment stage in R38+ cells, and to a lesser degree in R38- cells. Clustering analysis of cytometry and quantified Western blot data indicated that WT, R38+ and R38- HL-60 cells exhibited decreasing correlation between phenotypic markers and signaling factor expression. Thus differentiation induction therapy resistance can develop in stages, with initial partial RA resistance and moderate vitamin D3 responsiveness (unilineage maturation block), followed by bilineage maturation block and progressive signaling defects, notably the reduced expression of Vav1, Fgr, and c-Raf. PMID:24922062

Lactation persistency as a component trait of the selection index and increase in reliability by using single nucleotide polymorphism in net merit defined as the first five lactation milk yields and herd life.

PubMed

Togashi, K; Hagiya, K; Osawa, T; Nakanishi, T; Yamazaki, T; Nagamine, Y; Lin, C Y; Matsumoto, S; Aihara, M; Hayasaka, K

2012-08-01

We first sought to clarify the effects of discounted rate, survival rate, and lactation persistency as a component trait of the selection index on net merit, defined as the first five lactation milks and herd life (HL) weighted by 1 and 0.389 (currently used in Japan), respectively, in units of genetic standard deviation. Survival rate increased the relative economic importance of later lactation traits and the first five lactation milk yields during the first 120 months from the start of the breeding scheme. In contrast, reliabilities of the estimated breeding value (EBV) in later lactation traits are lower than those of earlier lactation traits. We then sought to clarify the effects of applying single nucleotide polymorphism (SNP) on net merit to improve the reliability of EBV of later lactation traits to maximize their increased economic importance due to increase in survival rate. Net merit, selection accuracy, and HL increased by adding lactation persistency to the selection index whose component traits were only milk yields. Lactation persistency of the second and (especially) third parities contributed to increasing HL while maintaining the first five lactation milk yields compared with the selection index whose only component traits were milk yields. A selection index comprising the first three lactation milk yields and persistency accounted for 99.4% of net merit derived from a selection index whose components were identical to those for net merit. We consider that the selection index comprising the first three lactation milk yields and persistency is a practical method for increasing lifetime milk yield in the absence of data regarding HL. Applying SNP to the second- and third-lactation traits and HL increased net merit and HL by maximizing the increased economic importance of later lactation traits, reducing the effect of first-lactation milk yield on HL (genetic correlation (rG) = -0.006), and by augmenting the effects of the second- and third-lactation milk yields on HL (rG = 0.118 and 0.257, respectively).

2-Cys peroxiredoxin is required in successful blood-feeding, reproduction, and antioxidant response in the hard tick Haemaphysalis longicornis.

PubMed

Kusakisako, Kodai; Galay, Remil Linggatong; Umemiya-Shirafuji, Rika; Hernandez, Emmanuel Pacia; Maeda, Hiroki; Talactac, Melbourne Rio; Tsuji, Naotoshi; Mochizuki, Masami; Fujisaki, Kozo; Tanaka, Tetsuya

2016-08-19

Ticks are obligate hematophagous arthropods that feed on vertebrate blood that contains iron. Ticks also concentrate host blood with iron; this concentration of the blood leads to high levels of iron in ticks. The host-derived iron reacts with oxygen in the tick body and this may generate high levels of reactive oxygen species, including hydrogen peroxide (H2O2). High levels of H2O2 cause oxidative stress in organisms and therefore, antioxidant responses are necessary to regulate H2O2. Here, we focused on peroxiredoxin (Prx), an H2O2-scavenging enzyme in the hard tick Haemaphysalis longicornis. The mRNA and protein expression profiles of 2-Cys peroxiredoxin (HlPrx2) in H. longicornis were investigated in whole ticks and internal organs, and developmental stages, using real-time PCR and Western blot analysis during blood-feeding. The localization of HlPrx2 proteins in tick tissues was also observed by immunostaining. Moreover, knockdown experiments of HlPrx2 were performed using RNA interference to evaluate its function in ticks. Real-time PCR showed that HlPrx2 gene expression in whole ticks and internal organs was significantly upregulated by blood-feeding. However, protein expression, except in the midgut, was constant throughout blood-feeding. Knockdown of the HlPrx2 gene caused significant differences in the engorged body weight, egg weight and hatching rate for larvae as compared to the control group. Finally, detection of H2O2 after knockdown of HlPrxs in ticks showed that the concentration of H2O2 significantly increased before and after blood-feeding. Therefore, HlPrx2 can be considered important for successful blood-feeding and reproduction through the regulation of H2O2 concentrations in ticks before and after blood-feeding. This study contributes to the search for a candidate target for tick control and further understanding of the tick's oxidative stress coping mechanism during blood-feeding.

Effect of reverse photoperiod on in vitro regeneration and piperine production in Piper nigrum L.

PubMed

Ahmad, Nisar; Abbasi, Bilal Haider; Fazal, Hina; Khan, Mubarak Ali; Afridi, Muhammad Siddique

2014-01-01

In this study, a novel approach for in vitro regeneration of Piper nigrum L. has been applied in order to increase healthy biomass, phytochemicals and piperine production via reverse photoperiod (16hD/8hL). Leaf portions of the seed-derived plants were placed on an MS-medium fortified with different PGRs. Under 16hD/8hL, thidiazuron (TDZ; 4.0 mg L⁻¹) and BA (1.5 mg L⁻¹) was found to be the most effective (<90%) in callus induction. Two concentrations (1.5, 2.0 mg L⁻¹) of the IBA produced>80% shoots from callus cultures. Healthy shoots were transferred to rooting medium and higher percentage of rooting (<90%) was observed on IBA (1.5 mg L⁻¹). These in vitro tissues were subjected to amino acid analysis, spectrophotometry, and HPLC. ARG, SER, THR, and TYR were the most abundant components out of 17 amino acids. Higher amino acid production was observed under normal photoperiod (16hL/8hD) than under reverse photoperiod (16hD/8hL). The highest total phenolic content (TPC; 9.91 mg/g-DW) and flavonoid content (7.38 mg/g-DW) were observed in callus cultures incubated under 16hL/8hD than other tissues incubated under 16hD/8hL photoperiod. Higher DPPH and PoMo activities were observed in tissues incubated under 16hL/8hD photoperiod, while ABTS and Fe²⁺ chelating activities were found higher in tissues incubated under reverse photoperiod. Significant quantities of piperine content were observed in all tissues except callus cultures. These results suggest that reverse photoperiod is a promising approach for callus induction, phytochemicals and piperine production for commercial applications. Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Crystal structures of seven molecular salts derived from benzylamine and organic acidic components

NASA Astrophysics Data System (ADS)

Wen, Xianhong; Jin, Xiunan; Lv, Chengcai; Jin, Shouwen; Zheng, Xiuqing; Liu, Bin; Wang, Daqi; Guo, Ming; Xu, Weiqiang

2017-07-01

Cocrystallization of the commonly available organic amine, benzylamine, with a series of organic acids gave a total of seven molecular salts with the compositions: (benzylamine): (p-toluenesulfonic acid) (1) [(HL)+ · (tsa-)], (benzylamine): (o-nitrobenzoic acid) (2) [(HL+) · (onba)-], (benzylamine): (3,4-methylenedioxybenzoic acid) (3) [(HL+) · (mdba-)], (benzylamine): (mandelic acid) (4) [(HL+) · (mda-)], (benzylamine): (5-bromosalicylic acid)2(5) [(HL+) · (bsac-) · (Hbsac)], (benzylamine): (m-phthalic acid) (6) [(HL+) · (Hmpta-)], and (benzylamine)2: (trimesic acid) (7) [(HL+)2 · (Htma2-)]. The seven salts have been characterised by X-ray diffraction technique, IR, and elemental analysis, and the melting points of all the salts were also reported. And their structural and supramolecular aspects are fully analyzed. The result reveals that among the seven investigated crystals the NH2 groups in the benzylamine moieties are protonated when the organic acids are deprotonated, and the crystal packing is interpreted in terms of the strong charge-assisted Nsbnd H⋯O hydrogen bond formation between the ammonium and the deprotonated acidic groups. Except the Nsbnd H⋯O hydrogen bond, the Osbnd H⋯O hydrogen bonds (charge assisted or neutral) were also found at the salts 4-7. Further analysis of the crystal packing of the salts indicated that a different family of additional CHsbnd O/CH2sbnd O, CHsbnd π/CH2sbnd π, Osbnd O, and Osbnd Cπ associations contribute to the stabilization and expansion of the total high-dimensional (2D-3D) framework structures. For the coexistence of the various weak nonbonding interactions these structures adopted homo or hetero supramolecular synthons or both. Some classical supramolecular synthons, such as R42(8), R43(10) and R44(12), usually observed in organic solids of organic acids with amine, were again shown to be involved in constructing most of these hydrogen bonding networks.

A turn-on fluorescent chemosensor for Zn2+ ion: X-ray structure and application in cell imaging study

NASA Astrophysics Data System (ADS)

Ghosh, Koushik; Dey, Sudipto; Halder, Shibashis; Bhattacharjee, Aradhita; Rizzoli, Corrado; Roy, Partha

2016-08-01

The selective fluorescence zinc(II) sensing properties of a Schiff-base compound, 2-methoxy-6-(2-morpholinoethyliminomethyl)phenol (HL) have been explored. The emission intensity of HL in the presence of one equivalent of Zn2+ ion increases by about 25 times. Several other metal ions, except Cd2+ and Ni2+, have not been able to increase the emission intensity of HL significantly. The quantum yield and life-time of HL have also been increased in the presence of Zn2+ ions. The enhancement in fluorescence intensity of HL is mainly due to the restriction of ESIPT, CHEF and PET on complex formation. HL forms a complex with Zn2+ in 1:1 ratio as evidenced by Job's plot analysis and X-ray single crystal structure determination. Some theoretical calculations have been performed to get a better view on the nature of the observed electronic transitions. The probe has been applied for imaging of DLD-1, human colorectal adenocarcinoma cell.

Health literacy predicts change in physical activity self-efficacy among sedentary Latinas.

PubMed

Dominick, Gregory M; Dunsiger, Shira I; Pekmezi, Dorothy W; Marcus, Bess H

2013-06-01

Health literacy (HL) is associated with preventive health behaviors. Self-efficacy is a predictor of health behavior, including physical activity (PA); however, causal pathways between HL and self-efficacy for PA are unknown, especially among Latinas who are at risk for chronic disease. To explore this potential relationship, secondary analyses were conducted on data [Shortened Test of Functional Health Literacy in Adults (STOFHLA), PA self-efficacy, and socio-demographics] from a 6-month, randomized controlled trial of a print-based PA intervention (n = 89 Spanish-speaking Latinas). Linear regression models revealed associations between HL and baseline self-efficacy in addition to changes in self-efficacy at 6-months. After controlling for significant covariates, higher HL scores were associated with lower baseline PA self-efficacy. Regardless of treatment assignment, higher HL scores at baseline predicted greater changes in PA self-efficacy at 6-months. HL may contribute to Latinas' improved PA self-efficacy, though further research is warranted.

The X-15/HL-20 operations support comparison

NASA Technical Reports Server (NTRS)

Morris, W. Douglas

1993-01-01

During the 1960's, the United States X-15 rocket-plane research program successfully demonstrated the ability to support a reusable vehicle operating in a near-space environment. The similarity of the proposed HL-20 lifting body concept in general size, weight, and subsystem composition to that of the X-15 provided an opportunity for a comparison of the predicted support manpower and turnaround times with those experienced in the X-15 program. Information was drawn from both reports and discussions with X-15 program personnel to develop comparative operations and support data. Based on the assumption of comparability between the two systems, the predicted staffing levels, skill mix, and refurbishment times of an operational HL-20 appear to be similar to those experienced by the X-15 for ground support. However, safety, environmental, and support requirements have changed such that the HL-20 will face a different operating environment than existed at Edwards during the 1950's and 1960's. Today's operational standards may impose additional requirements on the HL-20 that will add to the maintenance and support burden estimate based on the X-15 analogy.

Simultaneous IUE and Ground Based Observations of SS Cygni and HL Canis Majoris

NASA Astrophysics Data System (ADS)

Mansperger, C. S.; Kaitchuck, R. H.; Garnavich, P.; Dinshaw, N.

1993-05-01

SS Cyg and HL CMa were observed by IUE for three consecutive nights in November of 1992. During the first two nights, simultaneous photometric ground based observations of SS Cyg were made at the Ball State University Observatory. SS Cyg and HL CMa were observed simultaneously with the 90-inch telescope at the Steward Observatory on the last two nights of this run. These spectroscopic observations covered the wavelength range of 4100 Angstroms to 5000 Angstroms, while the spectra taken with the short wavelength camera on IUE resulted in wavelength coverage from 1150 Angstroms to 1980 Angstroms. SS Cyg is a U Gem type dwarf nova with an orbital period of 6.6 hours. Good simultaneous UV and optical orbital coverage was obtained for this system. HL CMa is a Z Cam type dwarf nova with an outburst period of 18 days. The AAVSO reports that this system was in outburst 4 days after the observing run. Therefore, HL CMa may have been in a preoutburst state during these observations. The C IV and H \\beta emission lines appeared to have weakened during this time.

Highly selective and sensitive turn-on fluorescent sensor for detection of Al3+ based on quinoline-base Schiff base

NASA Astrophysics Data System (ADS)

Wang, Yang; Ma, Zhong-Ying; Zhang, De-Long; Deng, Jia-Li; Chen, Xiong; Xie, Cheng-Zhi; Qiao, Xin; Li, Qing-Zhong; Xu, Jing-Yuan

2018-04-01

A new aluminum ion fluorescent probe (4-(diethylamino)-2-hydroxybenzylidene)isoquinoline-1-carbohydrazide (HL1) has been conveniently synthesized and characterized. HL1 exhibited a highly selective and pronounced enhancement for Al3+ in the fluorescence emission over other common cations by forming a 2:1 complex, with a recognition mechanism based on excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT). The strong fluorescent emission can be observed even at ppm level concentration of the probe in the presence of Al3+ with 41 fold intensity enhancement at 545 nm. HL1 displays good linear relationship with Al3+ in the low concentration and the limit of detection is 8.08 × 10-8 mol/L. Similar molecules with different substituents on salicylaldehyde phenyl ring were synthesized for studying the structure-activity relationship. Density-functional theory (DFT) calculations are in agreement with the proposed mechanism. It is confirmed that HL1 could be used to detect Al3+ ions in real sample by fluorescence spectrometry and Al3+ ions in cells by bioimaging.

Simultaneous Semi-Distributed Model Calibration Guided by ...

EPA Pesticide Factsheets

Modelling approaches to transfer hydrologically-relevant information from locations with streamflow measurements to locations without such measurements continues to be an active field of research for hydrologists. The Pacific Northwest Hydrologic Landscapes (PNW HL) provide a solid conceptual classification framework based on our understanding of dominant processes. A Hydrologic Landscape code (5 letter descriptor based on physical and climatic properties) describes each assessment unit area, and these units average area 60km2. The core function of these HL codes is to relate and transfer hydrologically meaningful information between watersheds without the need for streamflow time series. We present a novel approach based on the HL framework to answer the question “How can we calibrate models across separate watersheds simultaneously, guided by our understanding of dominant processes?“. We should be able to apply the same parameterizations to assessment units of common HL codes if 1) the Hydrologic Landscapes contain hydrologic information transferable between watersheds at a sub-watershed-scale and 2) we use a conceptual hydrologic model and parameters that reflect the hydrologic behavior of a watershed. In this study, This work specifically tests the ability or inability to use HL-codes to inform and share model parameters across watersheds in the Pacific Northwest. EPA’s Western Ecology Division has published and is refining a framework for defining la

HL7 and DICOM based integration of radiology departments with healthcare enterprise information systems.

PubMed

Blazona, Bojan; Koncar, Miroslav

2007-12-01

Integration based on open standards, in order to achieve communication and information interoperability, is one of the key aspects of modern health care information systems. However, this requirement represents one of the major challenges for the Information and Communication Technology (ICT) solutions, as systems today use diverse technologies, proprietary protocols and communication standards which are often not interoperable. One of the main producers of clinical information in healthcare settings represent Radiology Information Systems (RIS) that communicate using widely adopted DICOM (Digital Imaging and COmmunications in Medicine) standard, but in very few cases can efficiently integrate information of interest with other systems. In this context we identified HL7 standard as the world's leading medical ICT standard that is envisioned to provide the umbrella for medical data semantic interoperability, which amongst other things represents the cornerstone for the Croatia's National Integrated Healthcare Information System (IHCIS). The aim was to explore the ability to integrate and exchange RIS originated data with Hospital Information Systems based on HL7's CDA (Clinical Document Architecture) standard. We explored the ability of HL7 CDA specifications and methodology to address the need of RIS integration HL7 based healthcare information systems. We introduced the use of WADO service interconnection to IHCIS and finally CDA rendering in widely used Internet explorers. The outcome of our pilot work proves our original assumption of HL7 standard being able to adopt radiology data into the integrated healthcare systems. Uniform DICOM to CDA translation scripts and business processes within IHCIS is desired and cost effective regarding to use of supporting IHCIS services aligned to SOA.

Ranolazine inhibits shear sensitivity of endogenous Na+ current and spontaneous action potentials in HL-1 cells

PubMed Central

Strege, Peter; Beyder, Arthur; Bernard, Cheryl; Crespo-Diaz, Ruben; Behfar, Atta; Terzic, Andre; Ackerman, Michael; Farrugia, Gianrico

2012-01-01

NaV1.5 is a mechanosensitive voltage-gated Na+ channel encoded by the gene SCN5A, expressed in cardiac myocytes and required for phase 0 of the cardiac action potential (AP). In the cardiomyocyte, ranolazine inhibits depolarizing Na+ current and delayed rectifier (IKr) currents. Recently, ranolazine was also shown to be an inhibitor of NaV1.5 mechanosensitivity. Stretch also accelerates the firing frequency of the SA node, and fluid shear stress increases the beating rate of cultured cardiomyocytes in vitro. However, no cultured cell platform exists currently for examination of spontaneous electrical activity in response to mechanical stimulation. In the present study, flow of solution over atrial myocyte-derived HL-1 cultured cells was used to study shear stress mechanosensitivity of Na+ current and spontaneous, endogenous rhythmic action potentials. In voltage-clamped HL-1 cells, bath flow increased peak Na+ current by 14 ± 5%. In current-clamped cells, bath flow increased the frequency and decay rate of AP by 27 ± 12% and 18 ± 4%, respectively. Ranolazine blocked both responses to shear stress. This study suggests that cultured HL-1 cells are a viable in vitro model for detailed study of the effects of mechanical stimulation on spontaneous cardiac action potentials. Inhibition of the frequency and decay rate of action potentials in HL-1 cells are potential mechanisms behind the antiarrhythmic effect of ranolazine. PMID:23018927

2-(3-Methoxyphenyl)-5-methyl-1,8-naphthyridin-4(1H)-one (HKL-1) induces G2/M arrest and mitotic catastrophe in human leukemia HL-60 cells

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

Hsu, Mei-Hua; Liu, Chin-Yu; Lin, Chiao-Min

2012-03-01

2-(3-Methoxyphenyl)-5-methyl-1,8-naphthyridin-4(1H)-one (HKL-1), a 2-phenyl-1,8-naphthyridin-4-one (2-PN) derivative, was synthesized and evaluated as an effective antimitotic agent in our laboratory. However, the molecular mechanisms are uncertain. In this study, HKL-1 was demonstrated to induce multipolar spindles, sustain mitotic arrest and generate multinucleated cells, all of which indicate mitotic catastrophe, in human leukemia HL-60 cells. Western blotting showed that HKL-1 induces mitotic catastrophe in HL-60 cells through regulating mitotic phase-specific kinases (down-regulating CDK1, cyclin B1, CENP-E, and aurora B) and regulating the expression of Bcl-2 family proteins (down-regulating Bcl-2 and up-regulating Bax and Bak), followed by caspase-9/-3 cleavage. These findings suggest that HKL-1more » appears to exert its cytotoxicity toward HL-60 cells in culture by inducing mitotic catastrophe. Highlights: ► HKL-1 is a potential antimitotic agent against HL-60 cells. ► HKL-1 induces spindle disruption and sustained resulted in mitotic catastrophe. ► CENP-E and aurora B protein expressions significantly reduced. ► Bcl-2 family protein expressions altered and caspase-9/-3 activation. ► HKL-1 is an attractive candidate for possible use as a novel antimitotic agent.« less

Molecular cloning of the tomato Hairless gene implicates actin dynamics in trichome-mediated defense and mechanical properties of stem tissue.

PubMed

Kang, Jin-Ho; Campos, Marcelo L; Zemelis-Durfee, Starla; Al-Haddad, Jameel M; Jones, A Daniel; Telewski, Frank W; Brandizzi, Federica; Howe, Gregg A

2016-10-01

Trichomes are epidermal structures that provide a first line of defense against arthropod herbivores. The recessive hairless (hl) mutation in tomato (Solanum lycopersicum L.) causes severe distortion of trichomes on all aerial tissues, impairs the accumulation of sesquiterpene and polyphenolic compounds in glandular trichomes, and compromises resistance to the specialist herbivore Manduca sexta Here, we demonstrate that the tomato Hl gene encodes a subunit (SRA1) of the highly conserved WAVE regulatory complex that controls nucleation of actin filaments in a wide range of eukaryotic cells. The tomato SRA1 gene spans a 42-kb region containing both Solyc11g013280 and Solyc11g013290 The hl mutation corresponds to a complex 3-kb deletion that removes the last exon of the gene. Expression of a wild-type SRA1 cDNA in the hl mutant background restored normal trichome development, accumulation of glandular trichome-derived metabolites, and resistance to insect herbivory. These findings establish a role for SRA1 in the development of tomato trichomes and also implicate the actin-cytoskeleton network in cytosolic control of specialized metabolism for plant defense. We also show that the brittleness of hl mutant stems is associated with altered mechanical and cell morphological properties of stem tissue, and demonstrate that this defect is directly linked to the mutation in SRA1. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Generic quality of life in persons with hearing loss: a systematic literature review.

PubMed

Nordvik, Øyvind; Laugen Heggdal, Peder O; Brännström, Jonas; Vassbotn, Flemming; Aarstad, Anne Kari; Aarstad, Hans Jørgen

2018-01-01

To the best of our knowledge, no empirically based consensus has been reached as to if, and to what extent, persons with hearing loss (HL) have reduced generic Quality of life (QoL). There seems to be limited knowledge regarding to what extent a hearing aid (HA) would improve QoL. The main aim of the present study was to review studies about the relationship between HL and QoL. A supporting aim was to study the association between distress and HL. Literature databases (Cinahl, Pub Med and Web of Science) were searched to identify relevant journal articles published in the period from January 2000 to March 17, 2016. We performed a primary search pertaining to the relationship between HL, HA and QoL (search number one) followed by a supporting search pertaining to the relationship between distress/mood/anxiety and HL (search number two). After checking for duplications and screening the titles of the papers, we read the abstracts of the remaining papers. The most relevant papers were read thoroughly, leaving us with the journal articles that met the inclusion criteria. Twenty journal articles were included in the present review: 13 were found in the primary search (HL and QoL), and seven in the supporting search (HL and distress). The literature yields equivocal findings regarding the association between generic QoL and HL. A strong association between distress and HL was shown, where distressed persons tend to have a lowered generic QoL. It is suggested that QoL is lowered among HL patients. Some studies suggest an increased generic QoL following the use of HA, especially during the first few months after initiation of treatment. Other studies suggest that HA use is one of several possible factors that contribute to improve generic QoL. The majority of the studies suggest that HL is associated with reduced generic QoL. Using hearing aids seem to improve general QoL at follow-up within the first year. HL is a risk factor for distress. Further research is needed to explore the relationship between HL and generic QoL, in addition to the importance of influencing variables on this relationship.

An unexpected Schiff base-type Ni(II) complex: Synthesis, crystal structures, fluorescence, electrochemical property and SOD-like activities

NASA Astrophysics Data System (ADS)

Chai, Lan-Qin; Zhang, Hong-Song; Huang, Jiao-Jiao; Zhang, Yu-Li

2015-02-01

An unexpected Schiff base-type Ni(II) complex, [Ni(L2)2]ṡCH3OH (HL2 = 1-(2-{[(E)-3, 5-dibromo-2-hydroxybenzylidene]amino}phenyl)ethanone oxime), has been synthesized via complexation of Ni(II) acetate tetrahydrate with HL1 (2-(3,5-dibromo-2-hydroxyphenyl)-4-methyl-1,2-dihydroquinazoline 3-oxide) originally. HL1 and its corresponding Ni(II) complex were characterized by IR, 1H NMR spectra, as well as by elemental analysis, UV-Vis and emission spectroscopy, respectively. Crystal structures of the ligand and complex have been determined by single-crystal X-ray diffraction. Each complex links two other molecules into an infinite 1-D chain via intermolecular hydrogen bonding interactions. Moreover, the electrochemical property of the nickle complex was studied by cyclic voltammetry. In addition, SOD-like activities of HL1 and Ni(II) complex were also investigated.

Coordination behavior of ligand based on NNS and NNO donors with ruthenium(III) complexes and their catalytic and DNA interaction studies

NASA Astrophysics Data System (ADS)

Manikandan, R.; Viswnathamurthi, P.

2012-11-01

Reactions of 2-acetylpyridine-thiosemicarbazone HL1, 2-acetylpyridine-4-methyl-thiosemicarbazone HL2, 2-acetylpyridine-4-phenyl-thiosemicarbazone HL3 and 2-acetylpyridine-semicarbazone HL4 with ruthenium(III) precursor complexes were studied and the products were characterized by analytical and spectral (FT-IR, electronic, EPR and EI-MS) methods. The ligands coordinated with the ruthenium(III) ion via pyridine nitrogen, azomethine nitrogen and thiolate sulfur/enolate oxygen. An octahedral geometry has been proposed for all the complexes based on the studies. All the complexes are redox active and display an irreversible and quasireversible metal centered redox processes. Further, the catalytic activity of the new complexes has been investigated for the transfer hydrogenation of ketones in the presence of isopropanol/KOH and the Kumada-Corriu coupling of aryl halides with aryl Grignard reagents. The DNA cleavage efficiency of new complexes has also been tested.

Modulation of cardiomyocyte activity using pulsed laser irradiated gold nanoparticles

PubMed Central

Gentemann, Lara; Kalies, Stefan; Coffee, Michelle; Meyer, Heiko; Ripken, Tammo; Heisterkamp, Alexander; Zweigerdt, Robert; Heinemann, Dag

2016-01-01

Can photothermal gold nanoparticle mediated laser manipulation be applied to induce cardiac contraction? Based on our previous work, we present a novel concept of cell stimulation. A 532 nm picosecond laser was employed to heat gold nanoparticles on cardiomyocytes. This leads to calcium oscillations in the HL-1 cardiomyocyte cell line. As calcium is connected to the contractility, we aimed to alter the contraction rate of native and stem cell derived cardiomyocytes. A contraction rate increase was particularly observed in calcium containing buffer with neonatal rat cardiomyocytes. Consequently, the study provides conceptual ideas for a light based, nanoparticle mediated stimulation system. PMID:28101410

Health literacy in type 2 diabetes patients: a systematic review of systematic reviews.

PubMed

Caruso, Rosario; Magon, Arianna; Baroni, Irene; Dellafiore, Federica; Arrigoni, Cristina; Pittella, Francesco; Ausili, Davide

2018-01-01

Aim To summarize, critically review, and interpret the evidence related to the systematic reviews on health literacy (HL) amongst type 2 diabetes mellitus (T2DM). Methods The methodology for this study consisted of a systematic review of systematic reviews, using the PRISMA statement and flowchart to select studies, and searching on PubMed, CINAHL, Scopus, and Cochrane. The search covered the period between January 2006 and June 2016. Results From the 115 identified record by the queries, only six systematic reviews were included, following a quality evaluation using AMSTAR. The included systematic reviews content was analyzed by the independent work of two authors, using a narrative synthesis approach. The findings of this study (i.e., main themes) are areas of consensus and gaps in knowledge. Areas of consensus are HL definition, HL measurement tools, and the relationship between T2DM patient knowledge (or literacy) and his/her HL. The gaps in knowledge were the assessment of the relations between HL and health outcomes and self-efficacy, the gender differences, the effectiveness of interventions to improve HL, the cost-effectiveness study of interventions to improve HL, and the understanding of the influence of organizational environment on HL. Conclusion This review provides a current state of knowledge to address clinical practice and research proposals. HL could be useful to personalize patients' follow-up and it should be routinely assessed in its three dimensions (i.e. functional, interactive and critical) to enhance patients' ability to cope with clinical recommendations. Future research should be mainly aimed to test the effectiveness of evidence-based interventions to improve HL amongst T2DM patients.

The Development of a Graphical User Interface Engine for the Convenient Use of the HL7 Version 2.x Interface Engine

PubMed Central

Kim, Hwa Sun; Cho, Hune

2011-01-01

Objectives The Health Level Seven Interface Engine (HL7 IE), developed by Kyungpook National University, has been employed in health information systems, however users without a background in programming have reported difficulties in using it. Therefore, we developed a graphical user interface (GUI) engine to make the use of the HL7 IE more convenient. Methods The GUI engine was directly connected with the HL7 IE to handle the HL7 version 2.x messages. Furthermore, the information exchange rules (called the mapping data), represented by a conceptual graph in the GUI engine, were transformed into program objects that were made available to the HL7 IE; the mapping data were stored as binary files for reuse. The usefulness of the GUI engine was examined through information exchange tests between an HL7 version 2.x message and a health information database system. Results Users could easily create HL7 version 2.x messages by creating a conceptual graph through the GUI engine without requiring assistance from programmers. In addition, time could be saved when creating new information exchange rules by reusing the stored mapping data. Conclusions The GUI engine was not able to incorporate information types (e.g., extensible markup language, XML) other than the HL7 version 2.x messages and the database, because it was designed exclusively for the HL7 IE protocol. However, in future work, by including additional parsers to manage XML-based information such as Continuity of Care Documents (CCD) and Continuity of Care Records (CCR), we plan to ensure that the GUI engine will be more widely accessible for the health field. PMID:22259723

The Development of a Graphical User Interface Engine for the Convenient Use of the HL7 Version 2.x Interface Engine.

PubMed

Kim, Hwa Sun; Cho, Hune; Lee, In Keun

2011-12-01

The Health Level Seven Interface Engine (HL7 IE), developed by Kyungpook National University, has been employed in health information systems, however users without a background in programming have reported difficulties in using it. Therefore, we developed a graphical user interface (GUI) engine to make the use of the HL7 IE more convenient. The GUI engine was directly connected with the HL7 IE to handle the HL7 version 2.x messages. Furthermore, the information exchange rules (called the mapping data), represented by a conceptual graph in the GUI engine, were transformed into program objects that were made available to the HL7 IE; the mapping data were stored as binary files for reuse. The usefulness of the GUI engine was examined through information exchange tests between an HL7 version 2.x message and a health information database system. Users could easily create HL7 version 2.x messages by creating a conceptual graph through the GUI engine without requiring assistance from programmers. In addition, time could be saved when creating new information exchange rules by reusing the stored mapping data. The GUI engine was not able to incorporate information types (e.g., extensible markup language, XML) other than the HL7 version 2.x messages and the database, because it was designed exclusively for the HL7 IE protocol. However, in future work, by including additional parsers to manage XML-based information such as Continuity of Care Documents (CCD) and Continuity of Care Records (CCR), we plan to ensure that the GUI engine will be more widely accessible for the health field.

Self-Management Skills in Chronic Disease Management: What Role Does Health Literacy Have?

PubMed

Mackey, Laura M; Doody, Catherine; Werner, Erik L; Fullen, Brona

2016-08-01

Self-management-based interventions can lead to improved health outcomes in people with chronic diseases, and multiple patient characteristics are associated with the development of self-management behaviors. Low health literacy (HL) has been implicated in poorer self-management behaviors and increased costs to health services. However, the mechanisms behind this relationship remain unclear. Therefore, the aim of the current review is to assess the association between HL and patient characteristics related to self-management behaviors (i.e., disease-related knowledge, beliefs, and self-efficacy). The review comprised 3 phases: 1) database searches, 2) eligibility screening, and 3) study quality assessment and strength of evidence. Inclusion criteria specified that a valid HL screening tool was used, that at least one self-management behavior was assessed, and that patients had a chronic condition. An initial search generated a total of 712 articles, of which 31 studies fulfilled the eligibility criteria. A consistent association was found between low HL and poorer disease-related knowledge in respiratory diseases, diabetes, and multiple disease categories. A significant association between low HL and poorer self-efficacy was reported in cardiovascular diseases, diabetes, human immunodeficiency virus, and multiple disease categories. HL was significantly associated with poorer beliefs in respiratory, musculoskeletal, and cardiovascular diseases. The findings from the current review suggest that low HL may affect behaviors necessary for the development of self-management skills. Given that self-management strategies are core components for effective treatment of a range of chronic diseases, low HL poses a considerable health concern. Further research is needed to understand the mediating influence of HL on disease-related knowledge, self-efficacy, and beliefs. From this, HL-sensitive, self-management interventions ought to be devised and implemented. © The Author(s) 2016.

Internal locus of control, health literacy and health, an Israeli cultural perspective.

PubMed

Baron-Epel, Orna; Levin-Zamir, Diane; Cohen, Vicki; Elhayany, Asher

2017-11-13

The association between health literacy (HL) and health outcomes, including self-perceived health (SPH) has been well documented. Yet the complexity of this association is not yet completely clear. Drawing on the Health Literacy Scale (HLS) study in Israel, we examined the association between HL, Internal Health Locus of Control (IHLOC) and SPH among Jews and Arabs. A face-to-face survey was conducted among 242 Arabs and 358 Jews. The questionnaire measured SPH, IHLOC and two measures of HL: a European HLScale (HLS-EU-16) and the Hebrew/Arabic Health Literacy Test (H/AHLT), based on the Short Test Of Functional Health Literacy in Adults. Analysis included multivariable logistic regressions and bootstrapping to identify mediation effects. Among Jews, IHLOC seems to be a significant mediator between HL and SPH. IHLOC was strongly associated with SPH (OR = 6.13; CI = 3.2, 11.8), while HL was not significantly associated directly with SPH. Similar results were observed when using the H/AHLT as a measure of HL. Among Arabs a different pattern emerges; IHLOC was neither associated with SPH nor was it a mediator of the association between HL and SPH. The two measures of HL seem to have different associations with SPH among Arabs, as only H/AHLT was associated significantly with SPH, and not HLS-EU-16. Thus, those with higher levels of IHLOC assess their health as better than those with low IHLOC only among Jews, and not among Arabs. IHLOC seems to be a significant mediator between HL and SPH among some cultures. Among Arabs, only functional HL seems to be positively associated with SPH. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Annual clinical updates in hematological malignancies: a continuing medical education series. Hodgkin lymphoma: 2011 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2011-10-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8,500 new patients annually and representing approximately 11% of all lymphomas in the United States. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence are used to optimize therapy for patients with limited or advanced stage disease. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem-cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, palliative chemotherapy, nonmyeloablative allogeneic transplant, or participation in a clinical trial should be considered. 2011 Wiley-Liss, Inc.

Hodgkin lymphoma: 2012 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2012-12-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,000 new patients annually and representing approximately 11% of all lymphomas in the United States. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence are used to optimize therapy for patients with limited or advanced stage disease. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, palliative chemotherapy, non-myeloablative allogeneic transplant or participation in a clinical trial should be considered. Copyright © 2012 Wiley Periodicals, Inc.

Temperature-dependent inotropic and lusitropic indices based on half-logistic time constants for four segmental phases in isovolumic left ventricular pressure-time curve in excised, cross-circulated canine heart.

PubMed

Mizuno, Ju; Mohri, Satoshi; Yokoyama, Takeshi; Otsuji, Mikiya; Arita, Hideko; Hanaoka, Kazuo

2017-02-01

Varying temperature affects cardiac systolic and diastolic function and the left ventricular (LV) pressure-time curve (PTC) waveform that includes information about LV inotropism and lusitropism. Our proposed half-logistic (h-L) time constants obtained by fitting using h-L functions for four segmental phases (Phases I-IV) in the isovolumic LV PTC are more useful indices for estimating LV inotropism and lusitropism during contraction and relaxation periods than the mono-exponential (m-E) time constants at normal temperature. In this study, we investigated whether the superiority of the goodness of h-L fits remained even at hypothermia and hyperthermia. Phases I-IV in the isovolumic LV PTCs in eight excised, cross-circulated canine hearts at 33, 36, and 38 °C were analyzed using h-L and m-E functions and the least-squares method. The h-L and m-E time constants for Phases I-IV significantly shortened with increasing temperature. Curve fitting using h-L functions was significantly better than that using m-E functions for Phases I-IV at all temperatures. Therefore, the superiority of the goodness of h-L fit vs. m-E fit remained at all temperatures. As LV inotropic and lusitropic indices, temperature-dependent h-L time constants could be more useful than m-E time constants for Phases I-IV.

The Supervisory Control System for the HL-2A Neutral Beam Injector

NASA Astrophysics Data System (ADS)

Li, Bo; Li, Li; Feng, Kun; Wang, Xueyun; Yang, Jiaxing; Huang, Zhihui; Kang, Zihua; Wang, Mingwei; Zhang, Guoqing; Lei, Guangjiu; Rao, Jun

2009-06-01

Supervisory control and protection system of the neutral beam injector (NBI) in the HL-2A tokamak is presented. The system is used for a safe coordination of all the main NBI subsystems. Because the system is based on computer networks with its transmission medium of optical fiber, its advantages in high operational stability, reliability, security and flexible functional expandability are clearly shown during the NBI commissioning and heating experiment in HL-2A.

Activity-guided isolation of cytotoxic bis-bibenzyl constituents from Dumortiera hirsuta.

PubMed

Toyota, Masao; Ikeda, Risa; Kenmoku, Hiromichi; Asakawa, Yoshinori

2013-01-01

Activity-guided fractionation of the ether extract of Dumortiera hirsute (Japanese liverwort), using cytotoxicity testing with cultured HL 60 and KB cells, resulted in the isolation of a new cytotoxic bis-bibenzyl compound, along with the two known bis-bibenzyls: isomarchantin C and isoriccardin C. The structural determination of the new bis-bibenzyl through extensive NMR spectral data indicated a derivative of marchantin A, which has been isolated from the liverwort Marchantia polymorpha. The cytotoxicity of the bis-bibenzyls was evaluated by the MTT (3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay using cultured HL 60 and KB cells.

Scavenger receptor mediates systemic RNA interference in ticks.

PubMed

Aung, Kyaw Min; Boldbaatar, Damdinsuren; Umemiya-Shirafuji, Rika; Liao, Min; Xuenan, Xuan; Suzuki, Hiroshi; Galay, Remil Linggatong; Tanaka, Tetsuya; Fujisaki, Kozo

2011-01-01

RNA interference is an efficient method to silence gene and protein expressions. Here, the class B scavenger receptor CD36 (SRB) mediated the uptake of exogenous dsRNAs in the induction of the RNAi responses in ticks. Unfed female Haemaphysalis longicornis ticks were injected with a single or a combination of H. longicornis SRB (HlSRB) dsRNA, vitellogenin-1 (HlVg-1) dsRNA, and vitellogenin receptor (HlVgR) dsRNA. We found that specific and systemic silencing of the HlSRB, HlVg-1, and HlVgR genes was achieved in ticks injected with a single dsRNA of HlSRB, HlVg-1, and HlVgR. In ticks injected first with HlVg-1 or HlVgR dsRNA followed 96 hours later with HlSRB dsRNA (HlVg-1/HlSRB or HlVgR/HlSRB), gene silencing of HlSRB was achieved in addition to first knockdown in HlVg-1 or HlVgR, and prominent phenotypic changes were observed in engorgement, mortality, and hatchability, indicating that a systemic and specific double knockdown of target genes had been simultaneously attained in these ticks. However, in ticks injected with HlSRB dsRNA followed 96 hours later with HlVg-1 or HlVgR dsRNAs, silencing of HlSRB was achieved, but no subsequent knockdown in HlVgR or HlVg-1 was observed. The Westernblot and immunohistochemical examinations revealed that the endogenous HlSRB protein was fully abolished in midguts of ticks injected with HlSRB/HlVg-1 dsRNAs but HlVg-1 was normally expressed in midguts, suggesting that HlVg-1 dsRNA-mediated RNAi was fully inhibited by the first knockdown of HlSRB. Similarly, the abolished localization of HlSRB protein was recognized in ovaries of ticks injected with HlSRB/HlVgR, while normal localization of HlVgR was observed in ovaries, suggesting that the failure to knock-down HlVgR could be attributed to the first knockdown of HlSRB. In summary, we demonstrated for the first time that SRB may not only mediate the effective knock-down of gene expression by RNAi but also play essential roles for systemic RNAi of ticks.

Scavenger Receptor Mediates Systemic RNA Interference in Ticks

PubMed Central

Aung, Kyaw Min; Boldbaatar, Damdinsuren; Umemiya-Shirafuji, Rika; Liao, Min; Xuenan, Xuan; Suzuki, Hiroshi; Linggatong Galay, Remil; Tanaka, Tetsuya; Fujisaki, Kozo

2011-01-01

RNA interference is an efficient method to silence gene and protein expressions. Here, the class B scavenger receptor CD36 (SRB) mediated the uptake of exogenous dsRNAs in the induction of the RNAi responses in ticks. Unfed female Haemaphysalis longicornis ticks were injected with a single or a combination of H. longicornis SRB (HlSRB) dsRNA, vitellogenin-1 (HlVg-1) dsRNA, and vitellogenin receptor (HlVgR) dsRNA. We found that specific and systemic silencing of the HlSRB, HlVg-1, and HlVgR genes was achieved in ticks injected with a single dsRNA of HlSRB, HlVg-1, and HlVgR. In ticks injected first with HlVg-1 or HlVgR dsRNA followed 96 hours later with HlSRB dsRNA (HlVg-1/HlSRB or HlVgR/HlSRB), gene silencing of HlSRB was achieved in addition to first knockdown in HlVg-1 or HlVgR, and prominent phenotypic changes were observed in engorgement, mortality, and hatchability, indicating that a systemic and specific double knockdown of target genes had been simultaneously attained in these ticks. However, in ticks injected with HlSRB dsRNA followed 96 hours later with HlVg-1 or HlVgR dsRNAs, silencing of HlSRB was achieved, but no subsequent knockdown in HlVgR or HlVg-1 was observed. The Westernblot and immunohistochemical examinations revealed that the endogenous HlSRB protein was fully abolished in midguts of ticks injected with HlSRB/HlVg-1 dsRNAs but HlVg-1 was normally expressed in midguts, suggesting that HlVg-1 dsRNA-mediated RNAi was fully inhibited by the first knockdown of HlSRB. Similarly, the abolished localization of HlSRB protein was recognized in ovaries of ticks injected with HlSRB/HlVgR, while normal localization of HlVgR was observed in ovaries, suggesting that the failure to knock-down HlVgR could be attributed to the first knockdown of HlSRB. In summary, we demonstrated for the first time that SRB may not only mediate the effective knock-down of gene expression by RNAi but also play essential roles for systemic RNAi of ticks. PMID:22145043

Synthesis, characterization, crystal structure, superoxide dismutase and biological activities of nickel (II) complexes with bidentate ligands possessing N and O donor atoms

NASA Astrophysics Data System (ADS)

Sangeeta, S.; Ahmad, K.; Noorussabah, N.; Bharti, S.; Mishra, M. K.; Sharma, S. R.; Choudhary, M.

2017-12-01

Two new Schiff bases 2-((E)-(4-bromo-2-chlorophenylimino)methyl)-4-bromophenol(HL1) and1-((E)-(4-bromo-2-chlorophenylimino)methyl)naphthalene-2-ol (HL2) and their new nickel (II) complexes [Ni(L1)2]·DMF(1) and [Ni(L2)2] (2) have been synthesized and characterized by various physico- chemical and spectroscopic methods. The solid-state structures of synthesized compounds were determined by single crystal X-ray crystallography, which revealed square planar geometry around Ni (II) ion. Infrared spectra, UV-Vis, thermal analysis and magnetic susceptibility measurements agreed with the observed crystal structures. The ligand (HL1) crystallized in the Orthorhombic system of the space group Pbca,a = 7.5485(4)Å, b = 11.5514(5) Å, c = 30.1370(14)Å, α = 90°, β = 90°, γ = 90°and Z = 8. Complex[Ni(L1)2]·DMF(1) crystallized in the Triclinic system of the space group P-1, a = 8.9954(3) Å, b = 9.4593(4) Å, c = 13.2657(5) Å, α = 101.478°, β = 99.595°, γ = 117.651°and Z = 2, whereas complex [Ni(L2)2]·(2) crystallized in the Monoclinic system of the space group P21/c, a = 9.301(9)Å, b = 12.149(8)Å, c = 13.792(10)Å, α = 90°, β = 106.35(4).°, γ = 90°and Z = 2. The Schiff bases (HL1and HL2) behaved as monobasic bidentate ligands possessing N and O donor atoms. The SOD activities of HL1 and its Ni (II) complex[Ni(L1)2]·DMF(1) have been measured using xanthine-xanthine oxidase as a source of superoxide radical and NBT assay as O2- scavenger. In vitro antimicrobial activities of the Ni(II) complexes (1) and (2)against Bacillus cereus and Staphylococcus aureus as Gram + ve and Salmonella typhi, Klebsiella pneumonia and Escherichia coli as Gram-ve species have been investigated comparing with the Schiff base ligands (HL1and HL2).

HL-10 in flight over lakebed

NASA Technical Reports Server (NTRS)

1969-01-01

The HL-10 lifting body is seen here in flight over Rogers Dry Lake at Edwards AFB. After the vehicle's fins were modified following its first flight, the HL-10 proved to be the best handling of the heavy-weight lifting bodies flown at Edwards Air Force Base. The HL-10 flew much better than the M2-F2, and pilots were eager to fly it. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

The relationship of prenatal maternal depression or anxiety to maternal caregiving behavior and infant behavior self-regulation during infant heel lance: an ethological time-based study of behavior.

PubMed

Warnock, Fay F; Craig, Kenneth D; Bakeman, Roger; Castral, Thaila; Mirlashari, Jila

2016-09-07

Sensitive and responsive maternal caregiving behavior strengthens infant self-regulatory capacities (HL), but this regulatory role may be diminished in some mothers with second-trimester prenatal exposure to depression and/ or anxiety (MDA). This study examined maternal and infant behavior during infant heel lance (HL) when mothers had or did not have MDA. Ethological methods and micro-analytic approaches capable of distinguishing and comparing time-based patterning in maternal and infant behavior were used to clarify biological mechanisms, such as MDA, that may underlie observed behavior. Aims were to examine group differences in caregiving behavior between mothers with and without MDA 5 min Pre-HL and 5 min Post-H, and relationships between MDA, maternal caregiving behavior and infant pain behavior self-regulation, concurrently. At second trimester, mothers were assessed for symptoms of mild-severe depression or anxiety. Mothers whose scores exceeded predetermined cut-off scores on one or more of the mental health measures were allocated to the MDA-exposure group, those below to the non-MDA-exposure group. Reliable observers, blinded to MDA status and study phases, coded video records of the caregiving behavior of each study mother for the full duration of the 5 min Pre-HL and 5 min Post-HL study phases. Group differences and associations between mean measures of maternal mental health scores, time-based measures of maternal behavior, and time-based measures of infant pain behavior regulation (previously coded) were concurrently analyzed using comparative and correlational statistics. MDA-exposed mothers spent significantly more time not embracing, engaging or responding to infant cues than maternal controls Pre-HL and Post-HL. MDA was associated with atypical maternal caregiving behavior, which in turn was related to atypical infant pain behavior self-regulation during and after the HL. Our findings have implication for practice. We recommend inclusion of mothers with MDA and their infants in interventions that strengthen the early mother-infant interaction and mother's regulatory caregiving role. MDA and maternal caregiving behavior must be considered in future infant pain studies to examine if they confound effectiveness of mother driven caregiving interventions for neonatal pain. We highlight the importance of examining maternal mental health throughout the perinatal and postnatal trajectory, and particularly the newborn period.

Predicting trauma patient mortality: ICD [or ICD-10-AM] versus AIS based approaches.

PubMed

Willis, Cameron D; Gabbe, Belinda J; Jolley, Damien; Harrison, James E; Cameron, Peter A

2010-11-01

The International Classification of Diseases Injury Severity Score (ICISS) has been proposed as an International Classification of Diseases (ICD)-10-based alternative to mortality prediction tools that use Abbreviated Injury Scale (AIS) data, including the Trauma and Injury Severity Score (TRISS). To date, studies have not examined the performance of ICISS using Australian trauma registry data. This study aimed to compare the performance of ICISS with other mortality prediction tools in an Australian trauma registry. This was a retrospective review of prospectively collected data from the Victorian State Trauma Registry. A training dataset was created for model development and a validation dataset for evaluation. The multiplicative ICISS model was compared with a worst injury ICISS approach, Victorian TRISS (V-TRISS, using local coefficients), maximum AIS severity and a multivariable model including ICD-10-AM codes as predictors. Models were investigated for discrimination (C-statistic) and calibration (Hosmer-Lemeshow statistic). The multivariable approach had the highest level of discrimination (C-statistic 0.90) and calibration (H-L 7.65, P= 0.468). Worst injury ICISS, V-TRISS and maximum AIS had similar performance. The multiplicative ICISS produced the lowest level of discrimination (C-statistic 0.80) and poorest calibration (H-L 50.23, P < 0.001). The performance of ICISS may be affected by the data used to develop estimates, the ICD version employed, the methods for deriving estimates and the inclusion of covariates. In this analysis, a multivariable approach using ICD-10-AM codes was the best-performing method. A multivariable ICISS approach may therefore be a useful alternative to AIS-based methods and may have comparable predictive performance to locally derived TRISS models. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

Photorespiration participates in the assimilation of acetate in Chlorella sorokiniana under high light.

PubMed

Xie, Xiujun; Huang, Aiyou; Gu, Wenhui; Zang, Zhengrong; Pan, Guanghua; Gao, Shan; He, Linwen; Zhang, Baoyu; Niu, Jianfeng; Lin, Apeng; Wang, Guangce

2016-02-01

The development of microalgae on an industrial scale largely depends on the economic feasibility of mass production. High light induces productive suspensions during cultivation in a tubular photobioreactor. Herein, we report that high light, which inhibited the growth of Chlorella sorokiniana under autotrophic conditions, enhanced the growth of this alga in the presence of acetate. We compared pigments, proteomics and the metabolic flux ratio in C. sorokiniana cultivated under high light (HL) and under low light (LL) in the presence of acetate. Our results showed that high light induced the synthesis of xanthophyll and suppressed the synthesis of chlorophylls. Acetate in the medium was exhausted much more rapidly in HL than in LL. The data obtained from LC-MS/MS indicated that high light enhanced photorespiration, the Calvin cycle and the glyoxylate cycle of mixotrophic C. sorokiniana. The results of metabolic flux ratio analysis showed that the majority of the assimilated carbon derived from supplemented acetate, and photorespiratory glyoxylate could enter the glyoxylate cycle. Based on these data, we conclude that photorespiration provides glyoxylate to speed up the glyoxylate cycle, and releases acetate-derived CO2 for the Calvin cycle. Thus, photorespiration connects the glyoxylate cycle and the Calvin cycle, and participates in the assimilation of supplemented acetate in C. sorokiniana under high light. © 2015 Institute of Oceanography, Chinese Academy of Sciences (IOCAS). New Phytologist © 2015 New Phytologist Trust.

The Influence of Health Literacy on Reach, Retention, and Success in a Worksite Weight Loss Program.

PubMed

Zoellner, Jamie; You, Wen; Almeida, Fabio; Blackman, Kacie C A; Harden, Samantha; Glasgow, Russell E; Linnan, Laura; Hill, Jennie L; Estabrooks, Paul A

2016-03-01

To examine if employee health literacy (HL) status moderated reach, retention, and weight outcomes in a worksite weight loss program. The study was a two-group cluster randomized controlled weight loss trial. The study was conducted in 28 worksites. Subjects comprised 1460 employees with a body mass index >25 kg/m(2). Two 12-month weight loss interventions targeted diet and physical activity behaviors: incentaHEALTH (INCENT; incentivized individually targeted Internet-based intervention) and Livin' My Weigh (LMW; less-intense quarterly newsletters). A validated three-item HL screening measure was self-completed at baseline. Weight was objectively assessed with the Health Spot scale at baseline and 12-month follow-up. The impact of HL on program effectiveness was assessed through fixed-effect parametric models that controlled for individual (i.e., age, gender, race, ethnicity, income, education) and worksite random effects. Enrolled employees had significantly higher HL status [13.54 (1.68)] as compared to unenrolled [13.04 (2.17)] (p < .001). This finding was consistent in both interventions. Also, HL moderated weight loss effects (beta = .66; SE = 027; p = .014) and losing >5% weight (beta = -1.53; SE = .77; p < .047). For those with lower baseline HL, the INCENT intervention produced greater weight loss outcomes compared to LMW. The HL level of employees retained was not significantly different from those lost to follow-up. HL influences reach and moderates weight effects. These findings underscore the need to integrate recruitment strategies and further evaluate programmatic approaches that attend to the needs of low-HL audiences. © The Author(s) 2016.

Autoimmune and Atopic Disorders and Risk of Classical Hodgkin Lymphoma

PubMed Central

Hollander, Peter; Rostgaard, Klaus; Smedby, Karin E.; Chang, Ellen T.; Amini, Rose-Marie; de Nully Brown, Peter; Glimelius, Bengt; Adami, Hans-Olov; Melbye, Mads; Glimelius, Ingrid; Hjalgrim, Henrik

2015-01-01

Results from previous investigations have shown associations between the risk of Hodgkin lymphoma (HL) and a history of autoimmune and atopic diseases, but it remains unknown whether these associations apply to all types of HL or only to specific subtypes. We investigated immune diseases and the risk of classical HL in a population-based case-control study that included 585 patients and 3,187 controls recruited from October 1999 through August 2002. We collected information on immune diseases through telephone interviews and performed serological analyses of specific immunoglobulin E reactivity. Tumor Epstein-Barr virus (EBV) status was determined for 498 patients. Odds ratios with 95% confidence intervals were calculated using logistic regression analysis. Rheumatoid arthritis was associated with a higher risk of HL (odds ratio (OR) = 2.63; 95% confidence interval (CI): 1.47, 4.70), especially EBV-positive HL (OR = 3.18; 95% CI: 1.23, 8.17), and with mixed-cellularity HL (OR = 4.25; 95% CI: 1.66, 10.90). HL risk was higher when we used proxies of severe rheumatoid arthritis, such as ever having received daily rheumatoid arthritis medication (OR = 3.98; 95% CI: 2.08, 7.62), rheumatoid arthritis duration of 6–20 years (OR = 3.80; 95% CI: 1.72, 8.41), or ever having been hospitalized for rheumatoid arthritis (OR = 7.36; 95% CI: 2.95, 18.38). Atopic diseases were not associated with the risk of HL. EBV replication induced by chronic inflammation in patients with autoimmune diseases might explain the higher risk of EBV-positive HL. PMID:26346543

Modeling Healthcare Processes Using Commitments: An Empirical Evaluation.

PubMed

Telang, Pankaj R; Kalia, Anup K; Singh, Munindar P

2015-01-01

The two primary objectives of this paper are: (a) to demonstrate how Comma, a business modeling methodology based on commitments, can be applied in healthcare process modeling, and (b) to evaluate the effectiveness of such an approach in producing healthcare process models. We apply the Comma approach on a breast cancer diagnosis process adapted from an HHS committee report, and presents the results of an empirical study that compares Comma with a traditional approach based on the HL7 Messaging Standard (Traditional-HL7). Our empirical study involved 47 subjects, and two phases. In the first phase, we partitioned the subjects into two approximately equal groups. We gave each group the same requirements based on a process scenario for breast cancer diagnosis. Members of one group first applied Traditional-HL7 and then Comma whereas members of the second group first applied Comma and then Traditional-HL7-each on the above-mentioned requirements. Thus, each subject produced two models, each model being a set of UML Sequence Diagrams. In the second phase, we repartitioned the subjects into two groups with approximately equal distributions from both original groups. We developed exemplar Traditional-HL7 and Comma models; we gave one repartitioned group our Traditional-HL7 model and the other repartitioned group our Comma model. We provided the same changed set of requirements to all subjects and asked them to modify the provided exemplar model to satisfy the new requirements. We assessed solutions produced by subjects in both phases with respect to measures of flexibility, time, difficulty, objective quality, and subjective quality. Our study found that Comma is superior to Traditional-HL7 in flexibility and objective quality as validated via Student's t-test to the 10% level of significance. Comma is a promising new approach for modeling healthcare processes. Further gains could be made through improved tooling and enhanced training of modeling personnel.

Modeling Healthcare Processes Using Commitments: An Empirical Evaluation

PubMed Central

2015-01-01

The two primary objectives of this paper are: (a) to demonstrate how Comma, a business modeling methodology based on commitments, can be applied in healthcare process modeling, and (b) to evaluate the effectiveness of such an approach in producing healthcare process models. We apply the Comma approach on a breast cancer diagnosis process adapted from an HHS committee report, and presents the results of an empirical study that compares Comma with a traditional approach based on the HL7 Messaging Standard (Traditional-HL7). Our empirical study involved 47 subjects, and two phases. In the first phase, we partitioned the subjects into two approximately equal groups. We gave each group the same requirements based on a process scenario for breast cancer diagnosis. Members of one group first applied Traditional-HL7 and then Comma whereas members of the second group first applied Comma and then Traditional-HL7—each on the above-mentioned requirements. Thus, each subject produced two models, each model being a set of UML Sequence Diagrams. In the second phase, we repartitioned the subjects into two groups with approximately equal distributions from both original groups. We developed exemplar Traditional-HL7 and Comma models; we gave one repartitioned group our Traditional-HL7 model and the other repartitioned group our Comma model. We provided the same changed set of requirements to all subjects and asked them to modify the provided exemplar model to satisfy the new requirements. We assessed solutions produced by subjects in both phases with respect to measures of flexibility, time, difficulty, objective quality, and subjective quality. Our study found that Comma is superior to Traditional-HL7 in flexibility and objective quality as validated via Student’s t-test to the 10% level of significance. Comma is a promising new approach for modeling healthcare processes. Further gains could be made through improved tooling and enhanced training of modeling personnel. PMID:26539985

Synthesis, characterization, photoluminescence and cytotoxic properties of novel luminescent Eu(III)complexes based on chromone Schiff base

NASA Astrophysics Data System (ADS)

Saif, M.; El-Shafiy, Hoda F.; Mashaly, Mahmoud M.; Eid, Mohamed F.; Nabeel, A. I.; Fouad, R.

2018-06-01

Three novel Eu(III) phosphor complexes, [Eu(HL)(OH2)2(C2H5OH)](NO3)2 (1), [Eu(HL)(Bpy)(NO3)2(EtOH)] (2) and [Eu(HL)(Phen)(NO3)2(H2O)] (3) (HL = (11E)-2-hydroxy-N/-((4-oxo-4H-chromen-3-yl)methylene)benzohydrazide; Bpy = 2,2/-bibyridyl and Phen = 1,10-phenanthroline) were prepared. Elemental, thermal, FT-IR and XRD methods were used to characterize their structural configuration. The HL behaves as a monoanionic tridentate ligand. The XRD analysis shows that the ligand and its Eu3+complexes are in nano domain. From fluorescence spectroscopy, all the prepared complexes are highly luminescent, having an impressive visual emission under UV excitation. The H2L and its Eu3+nano-complexes (1-3) were tested for their in vitro cytotoxicity against Ehrlich Ascites Carcinoma cell line (EAC). The Eu(III) nano-complexes (1-3) effectively inhibited EAC growth with IC50 value of 25 μM. The high antitumor activity of the Eu(III) nano-complexes (1-3) were attributed to its chemical structure, and nano size properties.

Synthesis and Analysis of the Structure, Diffusion and Cytotoxicity of Heterocyclic Platinum(IV) Complexes.

PubMed

Macias, Freddy J; Deo, Krishant M; Pages, Benjamin J; Wormell, Paul; Clegg, Jack K; Zhang, Yingjie; Li, Feng; Zheng, Gang; Sakoff, Jennette; Gilbert, Jayne; Aldrich-Wright, Janice R

2015-11-16

We have developed six dihydroxidoplatinum(IV) compounds with cytotoxic potential. Each derived from active platinum(II) species, these complexes consist of a heterocyclic ligand (HL) and ancillary ligand (AL) in the form [Pt(HL)(AL)(OH)2](2+), where HL is a methyl-functionalised variant of 1,10-phenanthroline and AL is the S,S or R,R isomer of 1,2-diaminocyclohexane. NMR characterisation and X-ray diffraction studies clearly confirmed the coordination geometry of the octahedral platinum(IV) complexes. The self-stacking of these complexes was determined using pulsed gradient stimulated echo nuclear magnetic resonance. The self-association behaviour of square planar platinum(II) complexes is largely dependent on concentration, whereas platinum(IV) complexes do not aggregate under the same conditions, possibly due to the presence of axial ligands. The cytotoxicity of the most active complex, exhibited in several cell lines, has been retained in the platinum(IV) form. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Retinoic acid induces nuclear accumulation of Raf1 during differentiation of HL-60 cells

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

Smith, James; Bunaciu, Rodica P.; Reiterer, Gudrun

All trans-retinoic acid (RA) is a standard therapeutic agent used in differentiation induction therapy treatment of acute promyelocytic leukemia (APL). RA and its metabolites use a diverse set of signal transduction pathways during the differentiation program. In addition to the direct transcriptional targets of the nuclear RAR and RXR receptors, signals derived from membrane receptors and the Raf-MEK-ERK pathway are required. Raf1 phosphorylation and the prolonged activation of Raf1 persisting during the entire differentiation process are required for RA-dependent differentiation of HL-60 cells. Here we identify a nuclear redistribution of Raf1 during the RA-induced differentiation of HL-60 cells. In addition,more » the nuclear accumulation of Raf1 correlates with an increase in Raf1 phosphorylated at serine 621. The serine 621 phosphorylated Raf1 is predominantly localized in the nucleus. The RA-dependent nuclear accumulation of Raf1 suggests a novel nuclear role for Raf1 during the differentiation process.« less

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

Carrasco-González, Carlos; Rodríguez, Luis F.; Galván-Madrid, Roberto

The first long-baseline ALMA campaign resolved the disk around the young star HL Tau into a number of axisymmetric bright and dark rings. Despite the very young age of HL Tau, these structures have been interpreted as signatures for the presence of (proto)planets. The ALMA images triggered numerous theoretical studies based on disk–planet interactions, magnetically driven disk structures, and grain evolution. Of special interest are the inner parts of disks, where terrestrial planets are expected to form. However, the emission from these regions in HL Tau turned out to be optically thick at all ALMA wavelengths, preventing the derivation of surfacemore » density profiles and grain-size distributions. Here, we present the most sensitive images of HL Tau obtained to date with the Karl G. Jansky Very Large Array at 7.0 mm wavelength with a spatial resolution comparable to the ALMA images. At this long wavelength, the dust emission from HL Tau is optically thin, allowing a comprehensive study of the inner disk. We obtain a total disk dust mass of (1–3) × 10{sup −3} M {sub ⊙}, depending on the assumed opacity and disk temperature. Our optically thin data also indicate fast grain growth, fragmentation, and formation of dense clumps in the inner densest parts of the disk. Our results suggest that the HL Tau disk may be actually in a very early stage of planetary formation, with planets not already formed in the gaps but in the process of future formation in the bright rings.« less

Comparative analysis of the bioenergetics of adult cardiomyocytes and nonbeating HL-1 cells: respiratory chain activities, glycolytic enzyme profiles, and metabolic fluxes.

PubMed

Monge, Claire; Beraud, Nathalie; Tepp, Kersti; Pelloux, Sophie; Chahboun, Siham; Kaambre, Tuuli; Kadaja, Lumme; Roosimaa, Mart; Piirsoo, Andres; Tourneur, Yves; Kuznetsov, Andrey V; Saks, Valdur; Seppet, Enn

2009-04-01

Comparative analysis of the bioenergetic parameters of adult rat cardiomyocytes (CM) and HL-1 cells with very different structure but similar cardiac phenotype was carried out with the aim of revealing the importance of the cell structure for regulation of its energy fluxes. Confocal microscopic analysis showed very different mitochondrial arrangement in these cells. The cytochrome content per milligram of cell protein was decreased in HL-1 cells by a factor of 7 compared with CM. In parallel, the respiratory chain complex activities were decreased by 4-8 times in the HL-1 cells. On the contrary, the activities of glycolytic enzymes, hexokinase (HK), and pyruvate kinase (PK) were increased in HL-1 cells, and these cells effectively transformed glucose into lactate. At the same time, the creatine kinase (CK) activity was significantly decreased in HL-1 cells. In conclusion, the results of this study comply with the assumption that in contrast to CM in which oxidative phosphorylation is a predominant provider of ATP and the CK system is a main carrier of energy from mitochondria to ATPases, in HL-1 cells the energy metabolism is based mostly on the glycolytic reactions coupled to oxidative phosphorylation through HK.

Architectural approaches for HL7-based health information systems implementation.

PubMed

López, D M; Blobel, B

2010-01-01

Information systems integration is hard, especially when semantic and business process interoperability requirements need to be met. To succeed, a unified methodology, approaching different aspects of systems architecture such as business, information, computational, engineering and technology viewpoints, has to be considered. The paper contributes with an analysis and demonstration on how the HL7 standard set can support health information systems integration. Based on the Health Information Systems Development Framework (HIS-DF), common architectural models for HIS integration are analyzed. The framework is a standard-based, consistent, comprehensive, customizable, scalable methodology that supports the design of semantically interoperable health information systems and components. Three main architectural models for system integration are analyzed: the point to point interface, the messages server and the mediator models. Point to point interface and messages server models are completely supported by traditional HL7 version 2 and version 3 messaging. The HL7 v3 standard specification, combined with service-oriented, model-driven approaches provided by HIS-DF, makes the mediator model possible. The different integration scenarios are illustrated by describing a proof-of-concept implementation of an integrated public health surveillance system based on Enterprise Java Beans technology. Selecting the appropriate integration architecture is a fundamental issue of any software development project. HIS-DF provides a unique methodological approach guiding the development of healthcare integration projects. The mediator model - offered by the HIS-DF and supported in HL7 v3 artifacts - is the more promising one promoting the development of open, reusable, flexible, semantically interoperable, platform-independent, service-oriented and standard-based health information systems.

Highly selective and sensitive turn-on fluorescent sensor for detection of Al3+ based on quinoline-base Schiff base.

PubMed

Wang, Yang; Ma, Zhong-Ying; Zhang, De-Long; Deng, Jia-Li; Chen, Xiong; Xie, Cheng-Zhi; Qiao, Xin; Li, Qing-Zhong; Xu, Jing-Yuan

2018-04-15

A new aluminum ion fluorescent probe (4-(diethylamino)-2-hydroxybenzylidene)isoquinoline-1-carbohydrazide (HL 1 ) has been conveniently synthesized and characterized. HL 1 exhibited a highly selective and pronounced enhancement for Al 3+ in the fluorescence emission over other common cations by forming a 2:1 complex, with a recognition mechanism based on excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT). The strong fluorescent emission can be observed even at ppm level concentration of the probe in the presence of Al 3+ with 41 fold intensity enhancement at 545 nm. HL 1 displays good linear relationship with Al 3+ in the low concentration and the limit of detection is 8.08 × 10 -8  mol/L. Similar molecules with different substituents on salicylaldehyde phenyl ring were synthesized for studying the structure-activity relationship. Density-functional theory (DFT) calculations are in agreement with the proposed mechanism. It is confirmed that HL 1 could be used to detect Al 3+ ions in real sample by fluorescence spectrometry and Al 3+ ions in cells by bioimaging. Copyright © 2018 Elsevier B.V. All rights reserved.

Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2018-05-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8500 new patients annually and representing approximately 10.2% of all lymphomas in the United States. HL is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Newer agents including brentuximab vedotin are now being incorporated into frontline therapy and these new combinations are becoming a standard of care. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered. © 2018 Wiley Periodicals, Inc.

Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2016-06-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,050 new patients annually and representing approximately 11.2% of all lymphomas in the United States. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Management of relapsed/refractory disease: High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered. © 2016 Wiley Periodicals, Inc.

Hodgkin lymphoma: 2014 update on diagnosis, risk-stratification, and management.

PubMed

Ansell, Stephen M

2014-07-01

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,200 new patients annually and representing approximately 11.5% of all lymphomas in the United States. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte-predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Management of relapsed/refractory disease: High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, palliative chemotherapy, nonmyeloablative allogeneic transplant, or participation in a clinical trial should be considered. © 2014 Wiley Periodicals, Inc.

Integrating radiology information systems with healthcare delivery environments using DICOM and HL7 standards.

PubMed

Blazona, Bojan; Koncar, Miroslav

2006-01-01

Integration based on open standards, in order to achieve communication and information interoperability, is one of the key aspects of modern health care information systems. Interoperability presents data and communication layer interchange. In this context we identified the HL7 standard as the world's leading medical Information and communication technology (ICT) standard for the business layer in healthcare information systems and we tried to explore the ability to exchange clinical documents with minimal integrated healthcare information systems (IHCIS) change. We explored HL7 Clinical Document Architecture (CDA) abilities to achieve radiology information system integration (DICOM) to IHCIS (HL7). We introduced the use of WADO service interconnection to IHCIS and finally CDA rendering in widely used Internet explorers.

Synthesis and structure of 1,3-dimethyl-5-(p-sulfonamide-phenylazo)-6-aminouracil and its Ni(II) complex: Topological insights and investigation for noncovalent interactions

NASA Astrophysics Data System (ADS)

Debnath, Diptanu; Roy, Subhadip; Purkayastha, Atanu; Bauzá, Antonio; Choudhury, Rupasree; Ganguly, Rakesh; Frontera, Antonio; Misra, Tarun Kumar

2017-08-01

The azo-derivative, 1,3-dimethyl-5-(p-sulfonamide-phenylazo)-6-aminouracil (HL) containing 6-aminouracil (a biomolecule) and sulfonamide functionality (commonly found in sulfa-drugs), and its Ni(II) complex, NiIIL2 were synthesized. Single-crystal X-ray diffraction studies show that the ligand (HL) consists of an E conformation about the azo-linkage with a nearly planar geometry and the complex possesses distorted square planar geometry. The H-bonded underlying networks of HL and NiIIL2 were topologically classified revealing distinct topological types, namely tts and hxl, respectively. Moreover, topology of molecular packings in HL and NiIIL2 has also been discussed. Density functional theory (DFT) calculations, at the M06-2X/def2TZVP level of theory, are employed to characterize a great variety of non-covalent interactions that explicitly show the importance of antiparallel stacking interactions established by π--π+ interactions and H-bonds in the self-assembled dimmers in HL and lp-π/C-H⋯π interactions in NiIIL2. The results of NMR and UV-vis spectroscopies evidence that the ligand exists in hydrazone-imine-keto (B) tautomeric form in solution. The ligand absorption bands consist of the overlapping bands of π→π* and n→π* transitions. The complex experiences electronic transitions that consist of basically ILCT in character with some sort of participation of the atomic d-orbitals of the nickel. The pKa value of the ligand is found to be 4.09.

TSLP promotes angiogenesis of human umbilical vein endothelial cells by strengthening the crosstalk between cervical cancer cells and eosinophils.

PubMed

Zhang, Bing; Wei, Chun-Yan; Chang, Kai-Kai; Yu, Jia-Jun; Zhou, Wen-Jie; Yang, Hui-Li; Shao, Jun; Yu, Jin-Jin; Li, Ming-Qing; Xie, Feng

2017-12-01

Our previous study demonstrated that thymic stromal lymphopoietin (TSLP) secreted by cervical cancer cells promotes angiogenesis and recruitment, and regulates the function of eosinophils (EOS). However, the function of TSLP in the crosstalk between EOS and vascular endothelial cells in cancer lesions remains unknown. The aim of the present study was to investigate the effect of EOS caused by TSLP in in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). The results of the present study revealed that recombinant human TSLP protein (rhTSLP) increased the secretion of vascular endothelial growth factor (VEGF), but not fibroblast growth factors, in HL-60-eosinophils (HL-60E). Compared with cervical cancer cells (HeLa or CasKi cells) or HL-60E alone, there were increased levels of interleukin (IL)-8 and VEGF in the co-culture system between cervical cancer cells, and HL-60E cells. This effect was strengthened by rhTSLP, but inhibited by inhibiting the TSLP signal with anti-human TSLP or TSLP receptor neutralizing antibodies. The results of the tube formation assays revealed that treatment with the supernatant from cervical cancer cells and/or HL-60E resulted in an increase in angiogenesis in HUVECs, which could be decreased by TSLP or TSLPR inhibitors. The results of the present study suggested that TSLP derived of cervical cancer cells may indirectly stimulate angiogenesis of HUVECs, by upregulating IL-8 and VEGF production, in a co-culture model between cervical cancer cells and EOS, therefore promoting the development of cervical cancer.

Economic Evaluation of Manitoba Health Lines in the Management of Congestive Heart Failure

PubMed Central

Cui, Yang; Doupe, Malcolm; Katz, Alan; Nyhof, Paul; Forget, Evelyn L.

2013-01-01

Objective: This one-year study investigated whether the Manitoba Provincial Health Contact program for congestive heart failure (CHF) is a cost-effective intervention relative to the standard treatment. Design: Individual patient-level, randomized clinical trial of cost-effective model using data from the Health Research Data Repository at the Manitoba Centre for Health Policy, University of Manitoba. Methods: A total of 179 patients aged 40 and over with a diagnosis of CHF levels II to IV were recruited from Winnipeg and Central Manitoba and randomized into three treatment groups: one receiving standard care, a second receiving Health Lines (HL) intervention and a third receiving Health Lines intervention plus in-house monitoring (HLM). A cost-effectiveness study was conducted in which outcomes were measured in terms of QALYs derived from the SF-36 and costs using 2005 Canadian dollars. Costs included intervention and healthcare utilization. Bootstrap-resampled incremental cost-effectiveness ratios were computed to take into account the uncertainty related to small sample size. Results: The total per-patient mean costs (including intervention cost) were not significantly different between study groups. Both interventions (HL and HLM) cost less and are more effective than standard care, with HL able to produce an additional QALY relative to HLM for $2,975. The sensitivity analysis revealed that there is an 85.8% probability that HL is cost-effective if decision-makers are willing to pay $50,000. Conclusion: Findings demonstrate that the HL intervention from the Manitoba Provincial Health Contact program for CHF is an optimal intervention strategy for CHF management compared to standard care and HLM. PMID:24359716

A deterministic, dynamic systems model of cow-calf production: The effects of breeding replacement heifers before mature cows over a 10-year horizon.

PubMed

Shane, D D; Larson, R L; Sanderson, M W; Miesner, M; White, B J

2017-10-01

Some cattle production experts believe that cow-calf producers should breed replacement heifers (nulliparous cows) before cows (primiparous and multiparous cows), sometimes referred to as providing a heifer lead time (tHL). Our objective was to model the effects different durations of tHL may have on measures of herd productivity, including the percent of the herd cycling before the end of the first 21 d of the breeding season (%C21), the percent of the herd pregnant at pregnancy diagnosis (%PPD), the distribution of pregnancy by 21-d breeding intervals, the kilograms of calf weaned per cow exposed (KPC), and the replacement percentage (%RH), using a deterministic, dynamic systems model of cow-calf production over a 10-yr horizon. We also wished to examine differences in the effect of tHL related to the primiparous duration of postpartum anestrus (dPPA). The study model examined 6 different dPPA for primiparous cows (60, 70, 80, 90, 100, or 110 d). The multiparous cow duration of postpartum anestrus was set to 60 d. The breeding season length for nulliparous cows was 63 d, as was the breeding season length for primiparous and multiparous cows. Nulliparous cows were modeled with a tHL of 0, 7, 14, 21, 28, 35, or 42 d. Results are reported for the final breeding season of the 10-yr horizon. Increasing tHL resulted in a greater %C21 for the herd and for primiparous cows. Length of tHL had minimal impact on the %PPD unless the dPPA was 80 d or greater. For a dPPA of 110 d, a 0 d tHL resulted in the herd having 88.1 %PPD. When tHL was 21 d, the %PPD increased to 93.0%. The KPC was 161.2 kg when the dPPA was 110 d and tHL was 0 d and improved to 183.2 kg when tHL was increased to 42 d. The %RH did not vary much unless the dPPA was 90 d or greater, but increasing tHL resulted in decreased %RH. Based on the model results, increasing tHL improves the production outcomes included in the analysis, but herds with dPPA of 90 d or greater had the greatest degree of improvement. For these herds, approximately two-thirds of the improvement in outcomes by increasing tHL from 0 d to 42 d was realized when tHL was 21 d. Costs are likely incurred when implementing tHL in a breeding management program, and an ideal tHL likely depends on the dPPA of the herd, the expected improvement in productivity, and the costs associated with increasing tHL. Determining the dPPA of a herd could help veterinarians and producers develop optimal herd management strategies.

Infectious, autoimmune, and allergic diseases and risk of Hodgkin lymphoma in children and adolescents: A Children’s Oncology Group (COG) study

PubMed Central

Linabery, Amy M.; Erhardt, Erik B.; Fonstad, Rachel K.; Ambinder, Richard F.; Bunin, Greta R.; Ross, Julie A.; Spector, Logan G.; Grufferman, Seymour

2014-01-01

An infectious origin for pediatric Hodgkin lymphoma (HL) has long been suspected and Epstein-Barr virus (EBV) has been implicated in a subset of cases. Increased HL incidence in children with congenital and acquired immunodeficiencies, consistent associations between autoimmune diseases and adult HL, and genome-wide association and other genetic studies together suggest immune dysregulation is involved in lymphomagenesis. Here, healthy control children identified by random digit dialing were matched on sex, race/ethnicity, and age to HL cases diagnosed in 1989-2003 at 0-14 years at Children’s Oncology Group institutions. Parents of 517 cases and 784 controls completed telephone interviews, including items regarding medical histories. Tumor EBV status was determined for 355 cases. Using conditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HL. Cases were more likely to have had an infection >1 year prior to HL diagnosis (OR=1.69, 95% CI:0.98-2.91); case siblings were also more likely to have had a prior infection (OR=2.04, 95% CI:1.01-4.14). Parental history of autoimmunity associated with increased EBV+ HL risk (OR=2.97, 95% CI:1.34-6.58), while having a parent (OR=1.47, 95% CI:1.01-2.14) or sibling (OR=1.62, 95% CI:1.11-2.36) with an allergy was associated with EBV− HL. These results may indicate true increased risk for infections and increased risk with family history of autoimmune and allergic conditions that varies by tumor EBV status, or they may be attributable to inaccurate recall. In addition to employing biomarkers to confirm the role of immune-modulating conditions in pediatric HL, future studies should focus on family-based designs. PMID:24523151

Autoimmune and Atopic Disorders and Risk of Classical Hodgkin Lymphoma.

PubMed

Hollander, Peter; Rostgaard, Klaus; Smedby, Karin E; Chang, Ellen T; Amini, Rose-Marie; de Nully Brown, Peter; Glimelius, Bengt; Adami, Hans-Olov; Melbye, Mads; Glimelius, Ingrid; Hjalgrim, Henrik

2015-10-01

Results from previous investigations have shown associations between the risk of Hodgkin lymphoma (HL) and a history of autoimmune and atopic diseases, but it remains unknown whether these associations apply to all types of HL or only to specific subtypes. We investigated immune diseases and the risk of classical HL in a population-based case-control study that included 585 patients and 3,187 controls recruited from October 1999 through August 2002. We collected information on immune diseases through telephone interviews and performed serological analyses of specific immunoglobulin E reactivity. Tumor Epstein-Barr virus (EBV) status was determined for 498 patients. Odds ratios with 95% confidence intervals were calculated using logistic regression analysis. Rheumatoid arthritis was associated with a higher risk of HL (odds ratio (OR) = 2.63; 95% confidence interval (CI): 1.47, 4.70), especially EBV-positive HL (OR = 3.18; 95% CI: 1.23, 8.17), and with mixed-cellularity HL (OR = 4.25; 95% CI: 1.66, 10.90). HL risk was higher when we used proxies of severe rheumatoid arthritis, such as ever having received daily rheumatoid arthritis medication (OR = 3.98; 95% CI: 2.08, 7.62), rheumatoid arthritis duration of 6-20 years (OR = 3.80; 95% CI: 1.72, 8.41), or ever having been hospitalized for rheumatoid arthritis (OR = 7.36; 95% CI: 2.95, 18.38). Atopic diseases were not associated with the risk of HL. EBV replication induced by chronic inflammation in patients with autoimmune diseases might explain the higher risk of EBV-positive HL. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Synthesis, magnetic, spectral, and antimicrobial studies of Cu(II), Ni(II) Co(II), Fe(III), and UO 2(II) complexes of a new Schiff base hydrazone derived from 7-chloro-4-hydrazinoquinoline

NASA Astrophysics Data System (ADS)

El-Behery, Mostafa; El-Twigry, Haifaa

2007-01-01

A new hydrazone ligand, HL, was prepared by the reaction of 7-chloro-4-hydrazinoquinoline with o-hydroxybenzaldehyde. The ligand behaves as monoprotic bidentate. This was accounted for as the ligand contains a phenolic group and its hydrogen atom is reluctant to be replaced by a metal ion. The ligand reacted with Cu(II), Ni(II), Co(II), Fe(III), and UO 2(II) ions to yield mononuclear complexes. In the case of Fe(III) ion two complexes, mono- and binuclear complexes, were obtained in the absence and presence of LiOH, respectively. Also, mixed ligand complexes were obtained from the reaction of the metal cations Cu(II), Ni(II) and Fe(III) with the ligand (HL) and 8-hydroxyquinoline (8-OHqu) in the presence of LiOH, in the molar ratio 1:1:1:1. It is clear that 8-OHqu behaves as monoprotic bidentate ligand in such mixed ligand complexes. The ligand, HL, and its metal complexes were characterized by elemental analyses, IR, UV-vis, mass, and 1H NMR spectra, as well as magnetic moment, conductance measurements, and thermal analyses. All complexes have octahedral configurations except Cu(II) complex which has an extra square-planar geometry, while Ni(II) mixed complex has also formed a tetrahedral configuration and UO 2(II) complex which formed a favorable pentagonal biprymidial geometry. Magnetic moment of the binuclear Fe(III) complex is quite low compared to calculated value for two iron ions complex and thus shows antiferromagnetic interactions between the two adjacent ferric ions. The HL and metal complexes were tested against one stain Gram positive bacteria ( Staphylococcus aureus), Gram negative bacteria ( Escherichia coli), and fungi ( Candida albicans). The tested compounds exhibited higher antibacterial acivities.

Alterations in adipokines in feline hepatic lipidosis.

PubMed

Mazaki-Tovi, M; Abood, S K; Segev, G; Schenck, P A

2013-01-01

Feline hepatic lipidosis (HL) is associated with alterations in lipid and carbohydrate metabolism. The adipokines, adiponectin, and leptin have lipid-lowering and insulin-sensitizing effects. Serum concentrations of adiponectin and leptin are altered in feline HL. Client-owned cats: 55 healthy and 45 with liver disease. Cats with liver disease were categorized as having HL (n = 20), HL and concurrent disease (n = 19), or other liver disease (n = 6), based on clinical signs, laboratory findings, abdominal ultrasound examination as well as liver cytopathology, histopathology, or both. Serum samples were collected and body condition score determined. Mean serum concentrations of adiponectin were higher in overweight cats with HL (4.5 μg/mL), HL and concurrent disease (4.4 μg/mL), or other liver disease (6.1 μg/mL), as compared with healthy cats (1.5 μg/mL; P < .001, P < .001, and P = .04, respectively). Mean serum concentration of leptin was higher in cats with HL (9.8 ng/mL) or HL and concurrent disease (10.7 ng/mL) than healthy cats (4.9 ng/mL, P < .001 and P < .001, respectively). Cats with other liver disease had leptin concentration (4.9 ng/mL) similar to healthy cats. Concentrations of adiponectin were correlated with alanine aminotransferase activity (r = 0.40, P = .0069), and concentrations of leptin were correlated with alkaline phosphatase activity (r = 0.42, P = .0051) in cats with liver disease. Adipokine concentrations are altered in feline HL. Increased concentrations of adiponectin are related to liver disease, whereas increased concentrations of leptin are specifically related to HL. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Risk of familial classical Hodgkin lymphoma by relationship, histology, age, and sex: a joint study from five Nordic countries.

PubMed

Kharazmi, Elham; Fallah, Mahdi; Pukkala, Eero; Olsen, Jörgen H; Tryggvadottir, Laufey; Sundquist, Kristina; Tretli, Steinar; Hemminki, Kari

2015-10-22

We aimed to provide the familial risk of classical Hodgkin lymphoma (HL) by relationship, histology, age at diagnosis, and sex. A cohort of 57,475 first-degree relatives of 13,922 HL patients diagnosed between 1955 and 2009 in 5 European countries was observed for HL incidence. The overall lifetime cumulative risk (CR) of HL in first-degree relatives of a patient with HL was 0.6%, which represents a threefold (standardized incidence ratio [SIR], 3.3; 95% confidence interval [CI], 2.8-3.9) increased risk over the general population risk. The risk in siblings (6.0-fold; 95% CI, 4.8- to 7.4-fold) was significantly higher than in parents and/or children (2.1-fold; 95% CI, 1.6- to 2.6-fold). Very high lifetime risk of HL was found for those with multiple affected first-degree relatives (13-fold; 95% CI, 2.8- to 39-fold) and for same-sex twins (57-fold; 95% CI, 21- to 125-fold). We found high familial risks between some concordant histologic subtypes of HL such as lymphocyte-rich (81-fold; 95% CI, 30- to 177-fold) and nodular sclerosis (4.6-fold; 95% CI, 2.9- to 7.0-fold) and also between some discordant subtypes. The familial risk in sisters (9.4-fold; 95% CI, 5.9- to 14-fold) was higher than in brothers (4.5-fold; 95% CI, 2.9- to 6.7-fold) or unlike-sex siblings (5.9-fold; 95% CI, 4.3- to 8.1-fold). The lifetime risk of HL was higher when first-degree relatives were diagnosed at early ages (before age 30 years). This study provides tangible absolute risk estimates for relatives of HL patients, which can be used as a sex-, age-, and family history-based risk calculator for classical HL by oncologists and genetic counselors. © 2015 by The American Society of Hematology.

A Document-Based EHR System That Controls the Disclosure of Clinical Documents Using an Access Control List File Based on the HL7 CDA Header.

PubMed

Takeda, Toshihiro; Ueda, Kanayo; Nakagawa, Akito; Manabe, Shirou; Okada, Katsuki; Mihara, Naoki; Matsumura, Yasushi

2017-01-01

Electronic health record (EHR) systems are necessary for the sharing of medical information between care delivery organizations (CDOs). We developed a document-based EHR system in which all of the PDF documents that are stored in our electronic medical record system can be disclosed to selected target CDOs. An access control list (ACL) file was designed based on the HL7 CDA header to manage the information that is disclosed.

Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma : New study concepts of the German Hodgkin Study Group.

PubMed

Baues, C; Semrau, R; Gaipl, U S; Bröckelmann, P J; Rosenbrock, J; Engert, A; Marnitz, S

2017-02-01

Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.

Impact of Co-Occurring Birth Defects on the Timing of Newborn Hearing Screening and Diagnosis

PubMed Central

Chapman, Derek A.; Stampfel, Caroline C.; Bodurtha, Joann N.; Dodson, Kelley M.; Pandya, Arti; Lynch, Kathleen B.; Kirby, Russell S.

2016-01-01

Purpose Early detection of hearing loss in all newborns and timely intervention are critical to children's cognitive, verbal, behavioral, and social development. The initiation of appropriate early intervention services before 6 months of age can prevent or reduce negative developmental consequences. The purpose of this study was to assess, using large, population-based registries, the effect of co-occurring birth defects (CBDs) on the timing and overall rate of hearing screening and diagnosis. Method The authors linked statewide data from newborn hearing screenings, a birth defects registry, and birth certificates to assess the timeliness of newborn hearing screening and diagnosis of hearing loss (HL) for infants with and without CBDs in 485 children with confirmed HL. Results Nearly one third (31.5%) of children with HL had 1 or more CBDs. The presence of CBDs prolonged the time of the initial infant hearing screening, which contributed to further delays in the subsequent diagnosis of HL. Conclusions Better coordination of HL assessment into treatment plans for children with CBDs may enable earlier diagnosis of HL and provide opportunities for intervention that will affect long-term developmental outcomes for these children. PMID:21940980

Genes encoded within 8q24 on the amplicon of a large extrachromosomal element are selectively repressed during the terminal differentiation of HL-60 cells.

PubMed

Hirano, Tetsuo; Ike, Fumio; Murata, Takehide; Obata, Yuichi; Utiyama, Hiroyasu; Yokoyama, Kazunari K

2008-04-02

Human acute myeloblastic leukemia HL-60 cells become resistant to differentiation during long-term cultivation. After 150 passages, double minute chromosomes (dmins) found in early-passaged cells are replaced by large extrachromosomal elements (LEEs). In a DNA library derived from a purified fraction of LEEs, 12.6% (23/183) of clones were assigned to 8q24 and 9.2% (17/183) were assigned to 14q11 in the human genome. Fluorescence in situ hybridization (FISH) revealed a small aberrant chromosome, which had not been found in early-passaged cells, in addition to the purified LEEs. We determined that each LEE consisted of six discontinuous segments in a region that extended for 4.4Mb over the 8q24 locus. Five genes, namely, Myc (a proto-oncogene), NSMCE2 (for a SUMO ligase), CCDC26 (for a retinoic acid-dependent modulator of myeloid differentiation), TRIB1 (for a regulator of MAPK kinase) and LOC389637 (for a protein of unknown function), were encoded by the amplicon. Breaks in the chromosomal DNA within the amplicon were found in the NSMCE2 and CCDC26 genes. The discontinuous structure of the amplicon unit of the LEEs was identical with that of dmins in HL-60 early-passaged cells. The difference between them seemed, predominantly, to be the number (10-15 copies per LEE versus 2 or 3 copies per dmin) of constituent units. Expression of the Myc, NSMCE2, CCDC26 and LOC389637 and TRIB1 genes was constitutive in all lines of HL-60 cells and that of the first four genes was repressed during the terminal differentiation of early-passaged HL-60 cells. We also detected abnormal transcripts of CCDC26. Our results suggest that these genes were selected during the development of amplicons. They might be amplified and, sometimes, truncated to contribute to the maintenance of HL-60 cells in an undifferentiated state.

Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells

PubMed Central

2010-01-01

Background Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT). Methods We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT. Results PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT. Conclusion The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells. PMID:20423495

Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells.

PubMed

Wan, Jennifer Man-Fan; Sit, Wai-Hung; Yang, Xiaotong; Jiang, Pingping; Wong, Leo Lap-Yan

2010-04-27

Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT). We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT. PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT. The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells.

Urinary orotic acid-to-creatinine ratios in cats with hepatic lipidosis.

PubMed

VanSteenhouse, J L; Dimski, D S; Swenson, D H; Taboada, J

1999-06-01

To determine urinary orotic acid (OA) concentration and evaluate the urinary OA-to-creatinine ratio (OACR) in cats with hepatic lipidosis (HL). 20 cats with HL and 20 clinically normal cats. Hepatic lipidosis was diagnosed on the basis of clinical signs, results of serum biochemical analyses, exclusion of other concurrent illness, and cytologic or histologic evaluation of liver biopsy specimens. Urine samples were collected from each cat and frozen at -20 C until assayed. Urine creatinine concentrations were determined, using an alkaline picrate method followed by spectrophotometric assay. Urine OA concentration was determined, using high-performance liquid chromatography. Minimum amount of detectable OA in feline urine was 1 microg/ml. Because of small interfering peaks near the base of the OA peak, the minimum quantifiable concentration of OA was determined to be 5 microg/ml. Urinary OACR was compared in both groups of cats. Differences in urinary OACR were not detected between clinically normal cats and cats with HL. Peaks were not detected for urinary OA in any of the 20 clinically normal cats. Of the 20 HL cats, 14 did not have detectable peaks for urinary OA. Of the 6 HL cats that had detectable urinary OA peaks, 3 had values of <5 microg/ml. Apparently, OACR does not increase significantly in cats with HL. Urinary OACR is not a useful diagnostic test for HL in cats.

Sagebrush carrying out hydraulic lift enhances surface soil nitrogen cycling and nitrogen uptake into inflorescences.

PubMed

Cardon, Zoe G; Stark, John M; Herron, Patrick M; Rasmussen, Jed A

2013-11-19

Plant roots serve as conduits for water flow not only from soil to leaves but also from wetter to drier soil. This hydraulic redistribution through root systems occurs in soils worldwide and can enhance stomatal opening, transpiration, and plant carbon gain. For decades, upward hydraulic lift (HL) of deep water through roots into dry, litter-rich, surface soil also has been hypothesized to enhance nutrient availability to plants by stimulating microbially controlled nutrient cycling. This link has not been demonstrated in the field. Working in sagebrush-steppe, where water and nitrogen limit plant growth and reproduction and where HL occurs naturally during summer drought, we slightly augmented deep soil water availability to 14 HL+ treatment plants throughout the summer growing season. The HL+ sagebrush lifted greater amounts of water than control plants and had slightly less negative predawn and midday leaf water potentials. Soil respiration was also augmented under HL+ plants. At summer's end, application of a gas-based (15)N isotopic labeling technique revealed increased rates of nitrogen cycling in surface soil layers around HL+ plants and increased uptake of nitrogen into HL+ plants' inflorescences as sagebrush set seed. These treatment effects persisted even though unexpected monsoon rainstorms arrived during assays and increased surface soil moisture around all plants. Simulation models from ecosystem to global scales have just begun to include effects of hydraulic redistribution on water and surface energy fluxes. Results from this field study indicate that plants carrying out HL can also substantially enhance decomposition and nitrogen cycling in surface soils.

The Effect of Limited Health Literacy on How Internet Users Learn About Diabetes.

PubMed

Yom-Tov, Elad; Marino, Barbara; Pai, Jennifer; Harris, Dawn; Wolf, Michael

2016-10-01

The Internet continues to be an important supplemental health information resource for an increasing number of U.S. adults, especially for those with a new or existing chronic condition. Here we examine how people use the Internet to learn about Type 2 diabetes and how health literacy (HL) influences this information-seeking behavior. We analyzed the searches of approximately 2 million people who queried for diabetes-related information on Microsoft's Bing search engine. The HL of searchers was imputed through a community-based HL score. Topics searched were categorized and subsequent websites were assessed for readability. Overall, diabetes information-seeking strategies via the Internet are similar among adults with limited and adequate HL skills. However, people with limited HL take a longer time to read pages that are quickly read by people with adequate HL and vice versa. Information seeking among the former is terminated prematurely, as is evident from a Hidden Markov Model of the search process. Our findings indicate that the reading level required to understand the majority of diabetes-related information is high. Especially on government websites, more than 80% of information requires a reading level corresponding to 7th grade or higher. Our results indicate that individuals with lower HL may disproportionately struggle with Internet searches and fail to get an equivalent benefit from this information resource compared to users with greater HL. Future interventions should target the quality and ease of navigation of health care websites and find ways to leverage other relevant professionals to encourage and promote successful information access on the Web.

[Health literacy of adults in Germany: Findings from the German Health Update (GEDA) study].

PubMed

Jordan, Susanne; Hoebel, Jens

2015-09-01

In today's information society, health literacy (HL) is considered important for health maintenance and disease management. In this context, dealing with health information is fundamental and requires different cognitive and social skills. The aim of this study was to investigate the distribution of HL levels in the adult population of Germany, and to identify associations with health behaviours and health status. The analyses were based on data from the German Health Update (GEDA) study, a cross-sectional survey of the German-speaking adult population of Germany, which was conducted from October 2013 to June 2014. Health literacy was assessed with the short form of the European Health Literacy Questionnaire (HLS EU-Q16), along with questions about socio-demographics, health behaviours, and health status. The HLS-EU-Q16 index could be calculated for 4845 respondents. According to the criteria of the HLS-EU-Q16, more than half of the adults had "adequate" HL (55.8 %). Every third person (31.9 %) had "problematic" and almost every eighth person (12.3 %) had "inadequate" HL. We found significant differences in HL by educational level, but no differences in HL by sex and age group. Certain health behaviours were positively associated with health literacy. A low HL level was associated with poorer physical and mental health. The results point to a need for action to improve HL in the adult population. The strengthening of health literacy should not solely aim at the promotion of individual skills, but also give high priority to the development of health-literate settings.

A generic, web-based clinical information system architecture using HL7 CDA: successful implementation in dermatological routine care.

PubMed

Schuler, Thilo; Boeker, Martin; Klar, Rüdiger; Müller, Marcel

2007-01-01

The requirements of highly specialized clinical domains are often underrepresented in hospital information systems (HIS). Common consequences are that documentation remains to be paper-based or external systems with insufficient HIS integration are used. This paper presents a solution to overcome this deficiency in the form of a generic framework based on the HL7 Clinical Document Architecture. The central architectural idea is the definition of customized forms using a schema-controlled XML language. These flexible form definitions drive the user interface, the data storage, and standardized data exchange. A successful proof-of-concept application in a dermatologic outpatient wound care department has been implemented, and is well accepted by the clinicians. Our work with HL7 CDA revealed the need for further practical research in the health information standards realm.

4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.

PubMed

Puppala, Manohar; Zhao, Xinghua; Casemore, Denise; Zhou, Bo; Aridoss, Gopalakrishnan; Narayanapillai, Sreekanth; Xing, Chengguo

2016-03-15

4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization. Copyright © 2016. Published by Elsevier Ltd.

Syntheses, characterization, superoxide dismutase, antimicrobial, crystal structure and molecular studies of copper (II) and nickel (II) complexes with 2-((E)-(2, 4-dibromophenylimino) methyl)-4-bromophenol as Schiff base ligand

NASA Astrophysics Data System (ADS)

Bharti, Sulakshna; Choudhary, Mukesh; Mohan, Bharti; Rawat, S. P.; Sharma, S. R.; Ahmad, Khursheed

2017-12-01

Three new copper (II) and nickel (II) complexes viz. [Cu(L)2](1a), [Cu(L)2](1b) and [Ni(L)2].DMF(2), where HL = 2-((E)-(2, 4-dibromophenylimino) methyl)-4-bromophenol, have been synthesized and characterized by using various physico-chemical and spectroscopic techniques. The crystal structures of Schiff base (HL) and their metal complexes (1a), (1b) and (2) were determined by single crystal X-ray diffraction. IR and UV-Vis spectra and magnetic susceptibility measurements agree with the observed crystal structures. The crystallographic and spectroscopic studies confirmed four coordinate environments around the metal (II) ions. The synthesized Schiff base ligand (HL) crystallizes in the orthorhombic system of the space group Pbca. Complex (1a) of HL was crystallized in the monoclinic system of the space group P21/c, a = 10.1712(9) Å, b = 10.9299(10) Å,c = 12.7684(11) Å,α = 90̊,β = 104.649(2)̊, γ = 90̊ and Z = 2 whereas complex (1b) and (2) crystallized in the triclinic system of the space group P-1, a = 11.499(5)Å, b = 11.598(5)Å, c = 12.211(5)Å, α = 98.860(5), β = 115.653(5),γ = 100.906(5) and Z = 2 for (1b), a = 9.080(6) Å, b = 9.545(8)Å, c = 9.545(8)Å, α = 101.43(4)º,β = 99.63(3)̊, γ = 117.71(2)º and Z = 1 for (2). The synthesized ligand (HL) was behaved as monobasic bidentate Schiff base ligand having N and O donor sites. The electron paramagnetic resonance spectra indicate a dx2-y2ground state (g|| > g⊥> 2.0023) for (1a) and (1b). Copper (II) complexes display X-band EPR spectra in 100% DMSO and 77 K, giving indicating dx2-y2ground state. Superoxide dismutase-like activities of HL and its complexes were investigated by nitrobluetetrazolium chloride-DMSO assay and IC50 values were evaluated. These complexes were also tested for their in vitro antimicrobial activities against two bacteria (E. coli and Salmonella typhi) and two fungi (Pencillium, Aspergillus sp.) comparing with the Schiff base. The antimicrobial results showed that the complexes were more biologically active compounds to the Schiff base (HL).

Cyclopentenone derivatives and polyhydroxylated steroids from the soft coral Sinularia acuta.

PubMed

Zhang, Nai-Xia; Tang, Xu-Li; van Ofwegen, Leen; Xue, Lei; Song, Wen-Juan; Li, Ping-Lin; Li, Guo-Qiang

2015-02-01

Four new polyhydroxylated steroids, 1-4, and the racemic form of cyclopentenone 9, together with four known steroids, 5-8, one known cyclopentenone derivative, 10, and one known butenolide derivative, 11, were isolated from the soft coral Sinularia acuta collected from Weizhou Island of Guangxi Province, P. R. China. Their structures were elucidated on the basis of spectroscopic analyses and by comparison of the corresponding data with those previously reported. The cytotoxicities of the isolates 1-11 in vitro against the selected tumor cell lines HL-60, HeLa, and K562 were evaluated. Compounds 2 and 5 showed potent cytotoxicities against HL-60 cell lines with IC50 values of 7.3 and 9.9 μM, respectively. Compounds 5 and 6 showed moderate activities against K562 cell lines with IC50 values of 10.9 and 11.7 μM, respectively, while compounds 1, 2, and 6 showed weak activities against HeLa cell lines with respective IC50 values of 44.8, 27.1, and 18.2 μM. This is the first report on chemical and bioactivity research of S. acuta. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines.

PubMed

van Nimwegen, Frederika A; Ntentas, Georgios; Darby, Sarah C; Schaapveld, Michael; Hauptmann, Michael; Lugtenburg, Pieternella J; Janus, Cecile P M; Daniels, Laurien; van Leeuwen, Flora E; Cutter, David J; Aleman, Berthe M P

2017-04-20

Hodgkin lymphoma (HL) survivors treated with radiotherapy and/or chemotherapy are known to have increased risks of heart failure (HF), but a radiation dose-response relationship has not previously been derived. A case-control study, nested in a cohort of 2617 five-year survivors of HL diagnosed before age 51 years during 1965 to 1995, was conducted. Cases (n = 91) had moderate or severe HF as their first cardiovascular diagnosis. Controls (n = 278) were matched to cases on age, sex, and HL diagnosis date. Treatment and follow-up information were abstracted from medical records. Mean heart doses and mean left ventricular doses (MLVD) were estimated by reconstruction of individual treatments on representative computed tomography datasets. Average MLVD was 16.7 Gy for cases and 13.8 Gy for controls ( P difference = .003). HF rate increased with MLVD: relative to 0 Gy, HF rates following MVLD of 1-15, 16-20, 21-25, and ≥26 Gy were 1.27, 1.65, 3.84, and 4.39, respectively ( P trend < .001). Anthracycline-containing chemotherapy increased HF rate by a factor of 2.83 (95% CI: 1.43-5.59), and there was no significant interaction with MLVD ( P interaction = .09). Twenty-five-year cumulative risks of HF following MLVDs of 0-15 Gy, 16-20 Gy, and ≥21 Gy were 4.4%, 6.2%, and 13.3%, respectively, in patients treated without anthracycline-containing chemotherapy, and 11.2%, 15.9%, and 32.9%, respectively, in patients treated with anthracyclines. We have derived quantitative estimates of HF risk in patients treated for HL following radiotherapy with or without anthracycline-containing chemotherapy. Our results enable estimation of HF risk for patients before treatment, during radiotherapy planning, and during follow-up. © 2017 by The American Society of Hematology.

Improved viability and activity of neutrophils differentiated from HL-60 cells by co-culture with adipose tissue-derived mesenchymal stem cells

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

Park, Yoon Shin; Lim, Goh-Woon; Cho, Kyung-Ah

Highlights: Black-Right-Pointing-Pointer Neutropenia is a principal complication of cancer treatment. Black-Right-Pointing-Pointer Co-culture of neutrophils with AD-MSC retained cell survival and proliferation and inhibited neutrophil apoptosis under serum starved conditions. Black-Right-Pointing-Pointer AD-MSC increased functions of neutrophil. Black-Right-Pointing-Pointer AD-MSC promoted the viability of neutrophils by enhancing respiratory burst through the expression of IFN-{alpha}, G-CSF, and TGF-{beta}. Black-Right-Pointing-Pointer AD-MSC can be used to improve immunity for neutropenia treatment. -- Abstract: Neutropenia is a principal complication of cancer treatment. We investigated the supportive effect of adipose tissue-derived mesenchymal stem cells (AD-MSCs) on the viability and function of neutrophils. Neutrophils were derived from HL-60 cellsmore » by dimethylformamide stimulation and cultured with or without AD-MSCs under serum-starved conditions to evaluate neutrophil survival, proliferation, and function. Serum starvation resulted in the apoptosis of neutrophils and decreased cell survival. The co-culture of neutrophils and AD-MSCs resulted in cell survival and inhibited neutrophil apoptosis under serum-starved conditions. The survival rate of neutrophils was prolonged up to 72 h, and the expression levels of interferon (IFN)-{alpha}, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, and transforming growth factor (TGF)-{beta} in AD-MSCs were increased after co-culture with neutrophils. AD-MSCs promoted the viability of neutrophils by inhibiting apoptosis as well as enhancing respiratory burst, which could potentially be mediated by the increased expression of IFN-{alpha}, G-CSF, and TGF-{beta}. Thus, we conclude that the use of AD-MSCs may be a promising cell-based therapy for increasing immunity by accelerating neutrophil function.« less

Internal loop/bulge and hairpin loop of the iron-responsive element of ferritin mRNA contribute to maximal iron regulatory protein 2 binding and translational regulation in the iso-iron-responsive element/iso-iron regulatory protein family.

PubMed

Ke, Y; Sierzputowska-Gracz, H; Gdaniec, Z; Theil, E C

2000-05-23

Iron-responsive elements (IREs), a natural group of mRNA-specific sequences, bind iron regulatory proteins (IRPs) differentially and fold into hairpins [with a hexaloop (HL) CAGUGX] with helical distortions: an internal loop/bulge (IL/B) (UGC/C) or C-bulge. C-bulge iso-IREs bind IRP2 more poorly, as oligomers (n = 28-30), and have a weaker signal response in vivo. Two trans-loop GC base pairs occur in the ferritin IRE (IL/B and HL) but only one in C-bulge iso-IREs (HL); metal ions and protons perturb the IL/B [Gdaniec et al. (1998) Biochemistry 37, 1505-1512]. IRE function (translation) and physical properties (T(m) and accessibility to nucleases) are now compared for IL/B and C-bulge IREs and for HL mutants. Conversion of the IL/B into a C-bulge by a single deletion in the IL/B or by substituting the HL CG base pair with UA both derepressed ferritin synthesis 4-fold in rabbit reticulocyte lysates (IRP1 + IRP2), confirming differences in IRP2 binding observed for the oligomers. Since the engineered C-bulge IRE was more helical near the IL/B [Cu(phen)(2) resistant] and more stable (T(m) increased) and the HL mutant was less helical near the IL/B (ribonuclease T1 sensitive) and less stable (T(m) decreased), both CG trans-loop base pairs contribute to maximum IRP2 binding and translational regulation. The (1)H NMR spectrum of the Mg-IRE complex revealed, in contrast to the localized IL/B effects of Co(III) hexaammine observed previously, perturbation of the IL/B plus HL and interloop helix. The lower stability and greater helix distortion in the ferritin IL/B-IRE compared to the C-bulge iso-IREs create a combinatorial set of RNA/protein interactions that control protein synthesis rates with a range of signal sensitivities.

Comparison of the influence of two models of mild stress on hippocampal brain-derived neurotrophin factor (BDNF) immunoreactivity in old age rats.

PubMed

Badowska-Szalewska, Ewa; Ludkiewicz, Beata; Krawczyk, Rafał; Melka, Natalia; Moryś, Janusz

2017-01-01

The way hippocampal neurons function during stress in old age (critical times of life) is dependent on brain derived neurotrophin factor (BDNF). This study examined the influence of acute and chronic forced swim (FS) or high-light open field (HL‑OF) stimulation on the density of BDNF immunoreactive (ir) neurons in the hippocampal pyramidal layers of CA1, CA2, CA3 regions and the granular layer of dentate gyrus (DG) in old (postnatal day 720; P720) Wistar Han rats. Our data showed that in comparison with non-stressed rats, acute FS caused a significant increase in the density of BDNF-ir neurons in CA2 and CA3, while acute HL-OF led to an increase in this factor in all hippocampal subfields with the exception of DG. However, the density of BDNF-ir cells remained unchanged after exposure to chronic FS or HL‑OF in the hippocampal regions in relation to the control rats. These results indicate that acute FS or HL-OF proved to be a stressor that induces an increase in the density of BDNF-ir pyramidal neurons, which was probably connected with up-regulation of HPA axis activity and short‑time memory processing of the stressful situation. Moreover, as far as the influence on BDNF-ir cells in hippocampus is concerned, chronic FS or HL-OF was not an aggravating factor for rats in the ontogenetic periods studied.

A standards-based clinical information system for HIV/AIDS.

PubMed

Stitt, F W

1995-01-01

To create a clinical data repository to interface the Veteran's Administration (VA) Decentralized Hospital Computer Program (DHCP) and a departmental clinical information system for the management of HIV patients. This system supports record-keeping, decision-making, reporting, and analysis. The database development was designed to overcome two impediments to successful implementations of clinical databases: (i) lack of a standard reference data model, and; (ii) lack of a universal standard for medical concept representation. Health Level Seven (HL7) is a standard protocol that specifies the implementation of interfaces between two computer applications (sender and receiver) from different vendors or sources of electronic data exchange in the health care environment. This eliminates or substantially reduces the custom interface programming and program maintenance that would otherwise be required. HL7 defines the data to be exchanged, the timing of the interchange, and the communication of errors to the application. The formats are generic in nature and must be configured to meet the needs of the two applications involved. The standard conceptually operates at the seventh level of the ISO model for Open Systems Interconnection (OSI). The OSI simply defines the data elements that are exchanged as abstract messages, and does not prescribe the exact bit stream of the messages that flow over the network. Lower level network software developed according to the OSI model may be used to encode and decode the actual bit stream. The OSI protocols are not universally implemented and, therefore, a set of encoding rules for defining the exact representation of a message must be specified. The VA has created an HL7 module to assist DHCP applications in exchanging health care information with other applications using the HL7 protocol. The DHCP HL7 module consists of a set of utility routines and files that provide a generic interface to the HL7 protocol for all DHCP applications. The VA's DHCP core modules are in standard use at 169 hospitals, and the role of the VA system in health care delivery has been discussed elsewhere. This development was performed at the Miami VA Medical Center Special Immunology Unit, where a database was created for an HIV patient registry in 1987. Over 2,300 patient have been entered into a database that supports a problem-oriented summary of the patient's clinical record. The interface to the VA DHCP was designed and implemented to capture information from the patient treatment file, pharmacy, laboratory, radiology, and other modules. We obtained a suite of programs for implementing the HL7 encoding rules from Columbia-Presbyterian Medical Center in New York, written in ANSI C. This toolkit isolates our application programs from the details of the HL7 encoding rules, and allows them to deal with abstract messages and the programming level. While HL7 has become a standard for healthcare message exchange, SQL (Structured Query Language) is the standard for database definition, data manipulation, and query. The target database (Stitt F.W. The Problem-Oriented Medical Synopsis: a patient-centered clinical information system. Proc 17 SCAMC. 1993:88-93) provides clinical workstation functionality. Medical concepts are encoded using a preferred terminology derived from over 15 sources that include the Unified Medical Language System and SNOMed International ( Stitt F.W. The Problem-Oriented Medical Synopsis: coding, indexing, and classification sub-model. Proc 18 SCAMC, 1994: in press). The databases were modeled using the Information Engineering CASE tools, and were written using relational database utilities, including embedded SQL in C (ESQL/C). We linked ESQL/C programs to the HL7 toolkit to allow data to be inserted, deleted, or updated, under transaction control. A graphical format will be used to display the entity-rel

C-type natriuretic peptide is synthesized and secreted from leukemia cell lines, peripheral blood cells, and peritoneal macrophages.

PubMed

Kubo, A; Isumi, Y; Ishizaka, Y; Tomoda, Y; Kangawa, K; Dohi, K; Matsuo, H; Minamino, N

2001-05-01

C-type natriuretic peptide (CNP) is the third member of the natriuretic peptide family. Cultured endothelial cells secrete CNP, and its secretion rate from the endothelial cells is augmented by lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha, which participate in the pathophysiology of inflammation. In this study, we investigated the regulation of CNP secretion from monocytes and macrophages to estimate its contribution to the progression of inflammation. CNP secretion rates from two human leukemia cell lines (THP-1 and HL-60), human peripheral blood lymphocytes, granulocytes, monocytes, monocyte-derived macrophages, and mouse peritoneal macrophages were measured under conditions with or without stimulation. Immunoreactive CNP levels in the culture media of these cells were measured by a specific radioimmunoassay. The secretion rates of CNP from THP-1 and HL-60 cells were augmented according to the degree of their differentiation into macrophage-like cells under the stimulation with phorbol ester. Peripheral blood monocytes also increased the CNP secretion rate after their differentiation into macrophages. Retinoic acid elicited synergistic effects on the CNP secretion rate from HL-60 cells when administered with lipopolysaccharide, interferon-gamma, interleukin-1beta, tumor necrosis factor-alpha, or phorbol ester. In contrast, the phorbol ester-stimulated CNP secretion rate from THP-1 cells was suppressed with dexamethasone, which inhibits monocyte differentiation into macrophage. The secretion rate of CNP from monocytes was shown to be regulated based on the degree of their differentiation. This study provides evidence that the monocyte/macrophage system is one of the sources of CNP, especially under inflammatory conditions.

Doses to Carotid Arteries After Modern Radiation Therapy for Hodgkin Lymphoma: Is Stroke Still a Late Effect of Treatment?

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

Maraldo, Maja V., E-mail: dra.maraldo@gmail.com; Brodin, Patrick; Aznar, Marianne C.

2013-10-01

Purpose: Hodgkin lymphoma (HL) survivors are at an increased risk of stroke because of carotid artery irradiation. However, for early-stage HL involved node radiation therapy (INRT) reduces the volume of normal tissue exposed to high doses. Here, we evaluate 3-dimensional conformal radiation therapy (3D-CRT), volumetric-modulated arc therapy (VMAT), and proton therapy (PT) delivered as INRT along with the extensive mantle field (MF) by comparing doses to the carotid arteries and corresponding risk estimates. Methods and Materials: We included a cohort of 46 supradiaphragmatic stage I-II classical HL patients. All patients were initially treated with chemotherapy and INRT delivered as 3D-CRTmore » (30 Gy). For each patient, we simulated MF (36 Gy) and INRT plans using VMAT and PT (30 Gy). Linear dose-response curves for the 20-, 25-, and 30-year risk of stroke were derived from published HL data. Risks of stroke with each technique were calculated for all patients. Statistical analyses were performed with repeated measures analysis of variance. Results: The mean doses to the right and left common carotid artery were significantly lower with modern treatment compared with MF, with substantial patient variability. The estimated excess risk of stroke after 20, 25, and 30 years was 0.6%, 0.86%, and 1.3% for 3D-CRT; 0.67%, 0.96%, and 1.47% for VMAT; 0.61%, 0.96%, and 1.33% for PT; and 1.3%, 1.72%, and 2.61% for MF. Conclusions: INRT reduces the dose delivered to the carotid arteries and corresponding estimated risk of stroke for HL survivors. Even for the subset of patients with lymphoma close to the carotid arteries, the estimated risk is low.« less

Photothermal gold nanoparticle mediated stimulation of cardiomyocyte beating (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kalies, Stefan; Gentemann, Lara; Coffee, Michelle; Zweigerdt, Robert; Heinemann, Dag; Heisterkamp, Alexander

2017-03-01

Photothermal manipulation of cells via heating of gold nanoparticles has proven to be an efficient tool for molecular delivery into cells via cell perforation with short laser pulses. We investigated a potential extension of this technique for cell stimulation of cardiomyocytes using a 532 nm and 850 ps laser system and a surface concentration of 0.5 μg/cm2 of 200 nm gold nanoparticles. The gold nanoparticles were unspecifically attached to the cardiomyocytes after an incubation period of three hours. The laser irradiation leads to a temperature rise directly at the particles of several hundred degrees K which evokes bubble formation and membrane perforation. We examined the effect of laser based photothermal manipulation at different laser powers, with different calcium concentrations, and for a cardiomyocyte-like cell line (HL1 cells), neonatal rat cardiomyocytes and human embryonic stem cell (hESC)-derived cardiomyocytes. Fast calcium oscillations in HL1 cells were observed in the presence and absence of extracellular calcium and most pronounced in the area next to the laser spot after irradiation. Within the laser spot, in particular high laser powers led to a single rise in calcium over a time period of several seconds. These results were confirmed in stem cell-derived cardiomyocytes. In the presence of normal and high calcium concentrations, the spontaneous contraction frequency increased after laser irradiation in neonatal rat cardiomyocytes. Consequently, gold nanoparticle mediated photothermal cell manipulation via pulsed lasers may serve as a potential pacemaker-technique in regenerative approaches, next to optogenetics.

Structural and catalytic properties of some azo-rhodanine Ruthenium(III) complexes

NASA Astrophysics Data System (ADS)

Shoair, A. F.; El-Bindary, A. A.; Abd El-Kader, M. K.

2017-09-01

Novel azo-rhodanine ruthenium(III) complexes of the type trans-[Ru(Ln)2(AsPh3)2]Cl (Ln = monobasic bidentate anions of 5-(4‧-methoxyphenylazo)-3-phenylamino-2-thioxothiazolidin-4-one (HL1), 5-(phenylazo)-3-phenylamino-2-thioxothiazolidin-4-one (HL2) and 5-(4‧-chlorophenylazo)-3-phenylamino-2-thioxothiazolidin-4-one (HL3); AsPh3 = triphenylarsine) have been synthesized and characterized by elemental analysis, spectroscopic (IR, 1H NMR and UV-VIS), magnetic, X-ray diffraction, mass spectra and thermal analysis techniques. These techniques confirm the formation of octahedral ruthenium(III) complexes. The Ru(III) complexes were tested as a catalysts for the oxidation of benzyl alcohol to benzaldehyde with N-methylmorpholine-N-oxide as a co-oxidant. The effect of time, temperature, and solvent were also studied and the mechanism of this catalytic oxidation reaction is suggested. Molecular docking was used to predict the binding between azo rhodanine derivatives (HLn) with the receptor of 3qum- immune system receptor of human prostate specific antigen (PSA) in a Fab sandwich with a high affinity and a PCa selective antibody.

Coordination-Directed Stacking and Aggregation-Induced Emission Enhancement of the Zn(II) Schiff Base Complex.

PubMed

Wang, Dan; Li, Shu-Mu; Zheng, Jian-Quan; Kong, Duan-Yang; Zheng, Xiang-Jun; Fang, De-Cai; Jin, Lin-Pei

2017-01-17

2-(Trityliminomethyl)-quinolin-8-ol (HL) and its Zn(II) complex were synthesized and characterized by single-crystal X-ray diffraction. HL is an unsymmetrical molecule and coordinated with Zn(II) ion to form ZnL 2 in the antiparallel-mode arrangement via Zn-O (hydroxyl group) and Zn-N (quinoline ring) of HL. A high degree of ZnL 2 molecules ordering stacking is formed by the coordination bonds and intermolecular π-π interactions, in which head-to-tail arrangement (J-mode stacking) for L - is found. HL is nonfluorescent and ZnL 2 is weakly fluorescent in THF. The fluorescence emission of ZnL 2 enhances in THF/H 2 O as H 2 O% (volume %) is above 60% and aggregates particles with several hundred nanometers are formed, which is confirmed by DLS data and TEM images. The J-aggregates stacking for L - in ZnL 2 results in aggregation-induced emission enhancement (AIEE) for ZnL 2 in THF/H 2 O. Theoretical computations based on B3LYP/6-31G(d, p) and TD-B3LYP/6-31G(d, p) methods were carried out. ESIPT is the supposed mechanism for fluorescent silence of HL, and fluorescence emission of ZnL 2 is attributed to the restriction of ESIPT process. The oscillator strength of ZnL 2 increases from 0.017 for monomer to 0.032 for trimer. It indicates that a high degree of ZnL 2 molecules ordering stacking in THF/H 2 O is of benefit to fluorescence enhancement. HL is an ESIPT-coupled AIEE chemosensor for Zn(II) with high selectivity and sensitivity in aqueous medium. HL can efficiently detect intracellular Zn(II) ions because of ESIPT-coupled AIEE property of ZnL 2 in mixed solvent.

Dinuclear lanthanide complexes based on amino alcoholate ligands: Structure, magnetic and fluorescent properties

NASA Astrophysics Data System (ADS)

Sun, Gui-Fang; Zhang, Cong-Ming; Guo, Jian-Ni; Yang, Meng; Li, Li-Cun

2017-05-01

Two binuclear lanthanide complexes [Ln2(hfac)6(HL)2] (LnIII = Dy(1), Tb(2); hfac = hexafluoroacetylacetonate, HL = (R)-2-amino-2-phenylethanol) have been successfully obtained by using amino alcoholate ligand. In two complexes, the Ln(III) ions are bridged by two alkoxido groups from HL ligands, resulting in binuclear complexes. The variable-temperature magnetic susceptibility studies indicate that there exists ferromagnetic interaction between two Ln(III) ions. Frequency dependent out-of-phase signals are observed for complex 1, suggesting SMM type behavior. Complexes 1 and 2 display intensely characteristic luminescent properties.

The development of MML (Medical Markup Language) version 3.0 as a medical document exchange format for HL7 messages.

PubMed

Guo, Jinqiu; Takada, Akira; Tanaka, Koji; Sato, Junzo; Suzuki, Muneou; Suzuki, Toshiaki; Nakashima, Yusei; Araki, Kenji; Yoshihara, Hiroyuki

2004-12-01

Medical Markup Language (MML), as a set of standards, has been developed over the last 8 years to allow the exchange of medical data between different medical information providers. MML Version 2.21 used XML as a metalanguage and was announced in 1999. In 2001, MML was updated to Version 2.3, which contained 12 modules. The latest version--Version 3.0--is based on the HL7 Clinical Document Architecture (CDA). During the development of this new version, the structure of MML Version 2.3 was analyzed, subdivided into several categories, and redefined so the information defined in MML could be described in HL7 CDA Level One. As a result of this development, it has become possible to exchange MML Version 3.0 medical documents via HL7 messages.

Synthesis, characterization and anticancer activity of new Schiff bases bearing neocryptolepine

NASA Astrophysics Data System (ADS)

Emam, Sanaa M.; El Sayed, Ibrahim E. T.; Ayad, Mohamed I.; Hathout, Heba M. R.

2017-10-01

The synthesis of new Shiff base ligands denoted L1, HL2 and HL3 starting from the appropriate aminoneocryptolepine and salicaldehyde were described. The chelation abilities of L1, HL2 and HL3 ligands towards Co(II), Ni(II), Cu(II) and Pd(II) salts have been studied. A series of square planar complexes containing Cu(II) salts, PdCl2 and octahedral chelates containing NiCl2, CoCl2 salts (2 and 7) have been isolated. Also, the pentacoordinated Co(II) complex [Co(L1)2Cl]·Cl.0.5H2O·1.25EtOH (1) has been prepared. The mode of bonding and geometrical structure of complexes has been confirmed by elemental analyses and different spectroscopic methods together with thermal, magnetic moment studies, molecular modeling and X-ray diffraction. Furthermore, the synthesized ligands, in comparison to some of their metal complexes were screened for their anticancer activity against colorectal adenocarcinoma (HT-29) cells. The results showed that Co(II) complexes (1 and 7) exhibited higher anticancer activity when compared to the corresponding ligands.

Hippocampal mGluR5 predicts an occurrence of helplessness behavior after repetitive exposure to uncontrollable stress.

PubMed

Yim, Yeong Shin; Lee, Jinu; Kim, Gun-Tae; Song, Teresa; Kim, Chul Hoon; Kim, Dong Goo

2012-06-21

An individual's behavior is generally based on genetic blueprint and previous experiences. A coping strategy, affected by personal interpretation of past events, can be determined by behavioral controllability of stress. In this study, we examined the relationship between the hippocampal mGluR5 expression and coping strategies to stress. Rats were exposed to stress via inescapable and unpredictable footshocks on PNDs 14 and 90. Coping strategies to stress were also measured. Hippocampal mGluR5 was found to be linked to the behavioral coping strategy, as it increased in rats that showed helplessness behavior (HL (+) group) and decreased in those that did not (HL (-) group). Also, the HL (+) group showed a lack of adaptation in a novel environment but the HL (-) group did not. The results suggest that mGluR5 has a pivotal role in the controllability-based coping strategy. Hippocampal mGluR5 could be a target molecule in the manipulation of neuropsychiatric conditions for which maladaptation is a part of behavioral consequences. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The development of a highly constrained health level 7 implementation guide to facilitate electronic laboratory reporting to ambulatory electronic health record systems.

PubMed

Sujansky, Walter V; Overhage, J Marc; Chang, Sophia; Frohlich, Jonah; Faus, Samuel A

2009-01-01

Electronic laboratory interfaces can significantly increase the value of ambulatory electronic health record (EHR) systems by providing laboratory result data automatically and in a computable form. However, many ambulatory EHRs cannot implement electronic laboratory interfaces despite the existence of messaging standards, such as Health Level 7, version 2 (HL7). Among several barriers to implementing laboratory interfaces is the extensive optionality within the HL7 message standard. This paper describes the rationale for and development of an HL7 implementation guide that seeks to eliminate most of the optionality inherent in HL7, but retain the information content required for reporting outpatient laboratory results. A work group of heterogeneous stakeholders developed the implementation guide based on a set of design principles that emphasized parsimony, practical requirements, and near-term adoption. The resulting implementation guide contains 93% fewer optional data elements than HL7. This guide was successfully implemented by 15 organizations during an initial testing phase and has been approved by the HL7 standards body as an implementation guide for outpatient laboratory reporting. Further testing is required to determine whether widespread adoption of the implementation guide by laboratories and EHR systems can facilitate the implementation of electronic laboratory interfaces.

Data Warehouse Design from HL7 Clinical Document Architecture Schema.

PubMed

Pecoraro, Fabrizio; Luzi, Daniela; Ricci, Fabrizio L

2015-01-01

This paper proposes a semi-automatic approach to extract clinical information structured in a HL7 Clinical Document Architecture (CDA) and transform it in a data warehouse dimensional model schema. It is based on a conceptual framework published in a previous work that maps the dimensional model primitives with CDA elements. Its feasibility is demonstrated providing a case study based on the analysis of vital signs gathered during laboratory tests.

Synthesis, structure, luminescence, and magnetic properties of a single-ion magnet "mer"-[tris(N-[(imidazol-4-yl)-methylidene]-DL-phenylalaninato)terbium(III) and related "fac"-DL-alaninato derivative.

PubMed

Yamauchi, Suguru; Fujinami, Takeshi; Matsumoto, Naohide; Mochida, Naotaka; Ishida, Takayuki; Sunatsuki, Yukinari; Watanabe, Masayuki; Tsuchimoto, Masanobu; Coletti, Cecilia; Re, Nazzareno

2014-06-16

Two Tb(III) complexes with the same N6O3 donor atoms but different coordination geometries, "fac"-[Tb(III)(HL(DL-ala))3]·7H2O (1) and "mer"-[Tb(III)(HL(DL-phe))3]·7H2O (2), were synthesized, where H2L(DL-ala) and H2L(DL-phe) are N-[(imidazol-4-yl)methylidene]-DL-alanine and -DL-phenylalanine, respectively. Each Tb(III) ion is coordinated by three electronically mononegative NNO tridentate ligands to form a coordination geometry of a tricapped trigonal prism. Compound 1 consists of enantiomers "fac"-[Tb(III)(HL(D-ala))3] and "fac"-[Tb(III)(HL(L-ala))3], while 2 consists of "mer"-[Tb(III)(HL(D-phe))2(HL(L-phe))] and "mer"-[Tb(III)(HL(D-phe))(HL(L-phe))2]. Magnetic data were analyzed by a spin Hamiltonian including the crystal field effect on the Tb(III) ion (4f(8), J = 6, S = 3, L = 3, gJ = 3/2, (7)F6). The Stark splitting of the ground state (7)F6 was evaluated from magnetic analysis, and the energy diagram pattern indicated easy-plane and easy-axis (Ising type) magnetic anisotropies for 1 and 2, respectively. Highly efficient luminescences with Φ = 0.50 and 0.61 for 1 and 2, respectively, were observed, and the luminescence fine structure due to the (5)D4 → (7)F6 transition is in good accordance with the energy diagram determined from magnetic analysis. The energy diagram of 1 shows an approximate single-well potential curve, whereas that of 2 shows a double- or quadruple-well potential within the (7)F6 multiplets. Complex 2 displayed an onset of the out-of-phase signal in alternating current (ac) susceptibility at a direct current bias field of 1000 Oe on cooling down to 1.9 K. A slight frequency dependence was recorded around 2 K. On the other hand, 1 did not show any meaningful out-of-phase ac susceptibility. Pulsed-field magnetizations of 1 and 2 were measured below 1.6 K, and only 2 exhibited magnetic hysteresis. This finding agrees well with the energy diagram pattern from crystal field calculation on 1 and 2. DFT calculation allowed us to estimate the negative charge distribution around the Tb(III) ion, giving a rationale to the different magnetic anisotropies of 1 and 2.

Cellulase and Xylanase Production from Three Isolates of Indigenous Endophytic Fungi

NASA Astrophysics Data System (ADS)

Yopi; Tasia, W.; Melliawati, R.

2017-12-01

Cellulases and hemicellulases have good potential to be used in energy production, in pulp, paper, textile industries, as well as in animal feed industries. Moreover, its utilization in food industries also cannot be ignored, among others, cellulase and xylanase roles in bakery, wine, and fruit and vegetables juice production. One of the potential enzyme source is endophytic fungi. Object of this study is to explore the potency of endophytic fungi isolated from medicinal plants as source of cellulolytic and xylanolytic enzymes. HL.47F.216 is endophytic fungi isolated from traditional medicinal plants ironwood tree was determined as xylanase producer. HL.51F.235 from pin-flower tree is cellulase producer, while CBN.6F.29 which produces both xylanase and cellulase is originated from Madagascar periwinkle. HL.47F.216 showed 2.5 cm in clear zone diameter and its xylanase activity was 0.262 U/mL with optimum condition pH 7 at 50°C. HL.51F.235 showed 2.4 cm clear zone diameter and 0.239 U/mL of cellulase activity at pH 5 and 70°C. CBN.6F.29 showed 2.8 cm and 0.394 U/mL (pH 5, 40°C) for its cellulase activity, while 2.3 cm and 0.439 U/mL (pH 8, 70°C) for its xylanase activity. Xylanase from HL.47F.216 and CBN.6F.29 showed low molecular masses of 20 kDa and 37-50 kDa, respectively. Molecular masses for cellulases from HL.51F.235 and CBN.6F.29 were 25 and 50 kDa for HL.51F.235 and 100 kDa for CBN.6F.29. Based on macroscopic and microscopic identification, fungal isolate CBN.6F.29 is a member of Class Coelomycetes, while HL.47F.216 was Acremonium sp. and HL.51F.235 was Aspergillus nigri.

Economic Impact of Hearing Loss and Reduction of Noise-Induced Hearing Loss in the United States.

PubMed

Neitzel, Richard L; Swinburn, Tracy K; Hammer, Monica S; Eisenberg, Daniel

2017-01-01

Hearing loss (HL) is pervasive and debilitating, and noise-induced HL is preventable by reducing environmental noise. Lack of economic analyses of HL impacts means that prevention and treatment remain a low priority for public health and environmental investment. This article estimates the costs of HL on productivity by building on established estimates for HL prevalence and wage and employment differentials between those with and without HL. We estimate that HL affects more than 13% of the working population. Not all HL can be prevented or treated, but if the 20% of HL resulting from excessive noise exposure were prevented, the economic benefit would be substantial-we estimate a range of $58 billion to $152 billion annually, with a core estimate of $123 billion. We believe this is a conservative estimate, because consideration of additional costs of HL, including health care and special education, would likely further increase the benefits associated with HL prevention. HL is costly and warrants additional emphasis in public and environmental health programs. This study represents an important first step in valuing HL prevention-in particular, prevention of noise-induced HL-where new policies and technologies appear promising.

Validation of self-reported health literacy questions among diverse English and Spanish-speaking populations.

PubMed

Sarkar, Urmimala; Schillinger, Dean; López, Andrea; Sudore, Rebecca

2011-03-01

Limited health literacy (HL) contributes to poor health outcomes and disparities, and direct measurement is often time-intensive. Self-reported HL questions have not been validated among Spanish-speaking and diverse English-speaking populations. To evaluate three self-reported questions: 1 "How confident are you filling out medical forms?"; 2 "How often do you have problems learning about your medical condition because of difficulty understanding written information?"; and 3 "How often do you have someone help you read hospital materials?" Answers were based on a 5-point Likert scale. This was a validation study nested within a trial of diabetes self-management support in the San Francisco Department of Public Health. English and Spanish-speaking adults with type 2 diabetes receiving primary care. Using the Test of Functional Health Literacy in Adults (s-TOFHLA) in English and Spanish as the reference, we classified HL as inadequate, marginal, or adequate. We calculated the C-index and test characteristics of the three questions and summative scale compared to the s-TOFHLA and assessed variations in performance by language, race/ethnicity, age, and education. Of 296 participants, 48% were Spanish-speaking; 9% were White, non-Hispanic; 47% had inadequate HL and 12% had marginal HL. Overall, 57% reported being confident with forms "somewhat" or less. The "confident with forms" question performed best for detecting inadequate (C-index = 0.82, (0.77-0.87)) and inadequate plus marginal HL (C index = 0.81, (0.76-0.86); p<0.01 for differences from other questions), and performed comparably to the summative scale. The "confident with forms" question and scale also performed best across language, race/ethnicity, educational attainment, and age. A single self-reported HL question about confidence with forms and a summative scale of three questions discriminated between Spanish and English speakers with adequate HL and those with inadequate and/or inadequate plus marginal HL. The "confident with forms" question or the summative scale may be useful for estimating HL in clinical research involving Spanish-speaking and English-speaking, chronically-ill, diverse populations.

Magnetic configuration flexibility of snowflake divertor for HL-2M [Analysis of snowflake divertor configurations for HL-2M

DOE PAGES

Zheng, G. Y.; Xu, X. Q.; Ryutov, D. D.; ...

2014-07-09

HL-2M (Li, 2013 [1]) is a tokamak device that is under construction. Based on the magnetic coils design of HL-2M, four kinds of divertor configurations are calculated by CORSICA code (Pearlstein et al., 2001 [2]) with the same main plasma parameters, which are standard divertor, exact snowflake divertor, snowflake-plus divertor and snowflake-minus divertor configurations. The potential properties of these divertors are analyzed and presented in this paper: low poloidal field area around X-point, connection length from outside mid-plane to the primary X-point, target plate design and magnetic field shear. The results show that the snowflake configurations not only can reducemore » the heat load at divertor target plates, but also may improve the magneto-hydrodynamic stability by stronger magnetic shear at the edge. Furthermore, a new divertor configuration, named “tripod divertor”, is designed by adjusting the positions of the two X-points according to plasma parameters and magnetic coils current of HL-2M.« less

The effects of transportation stress on Japanese quail (Coturnix Coturnix japonica) fed corn-based diet in comparison with wheat-based diet supplemented with xylanase and phytase.

PubMed

Mehraei Hamzekolaei, M H; Zamani Moghaddam, A K; Tohidifar, S S; Dehghani Samani, A; Heydari, A

2016-08-01

Harvesting, handling and transporting quails to the slaughterhouses, other farms and laboratories might covertly reduce their welfare. The aim of this study was to evaluate the effects of two major sources of energy in poultry nutrition on reducing transportation stress in Japanese quail (Coturnix Coturnix japonica). Male quails (n = 60) were divided into two groups. The first group was fed corn-based diet, and the second was fed wheat-based diet supplemented with xylanase and phytase. At the end of the experiment (day 35), quails were subjected to 80 km of transportation. Immediately on arrival and after 24 h, heterophil counts, lymphocyte counts and H:L ratios were measured. On arrival, H counts were lower, L counts were higher, and H:L ratios were lower for corn-fed group. After 24 h, wheat-fed group showed lower increment of H counts, greater increment of L counts and also decrement of H:L ratios rather than corn-fed group which showed increment of H:L ratios. However, these ratios were still lower in corn-fed group. Results indicate that corn-based diets can help Japanese quail to better resist transportation stress, although it seems that feeding wheat-based diets supplemented with xylanase and phytase could have positive effects for coping better with stress after journeys. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Leaf physiological versus morphological acclimation to high-light exposure at different stages of foliar development in oak.

PubMed

Rodríguez-Calcerrada, J; Reich, P B; Rosenqvist, E; Pardos, J A; Cano, F J; Aranda, I

2008-05-01

We investigated light acclimation in seedlings of the temperate oak Quercus petraea (Matt.) Liebl. and the co-occurring sub-Mediterranean oak Quercus pyrenaica Willd. Seedlings were raised in a greenhouse for 1 year in either 70 (HL) or 5.3% (LL) of ambient irradiance of full sunlight, and, in the following year, subsets of the LL-grown seedlings were transferred to HL either before leaf flushing (LL-HLBF plants) or after full leaf expansion (LL-HLAF plants). Gas exchange, chlorophyll a fluorescence, nitrogen fractions in photosynthetic components and leaf anatomy were examined in leaves of all seedlings 5 months after plants were moved from LL to HL. Differences between species in the acclimation of LL-grown plants to HL were minor. For LL-grown plants in HL, area-based photosynthetic capacity, maximum rate of carboxylation, maximum rate of electron transport and the effective photochemical quantum yield of photosystem II were comparable to those for plants grown solely in HL. A rapid change in nitrogen distribution among photosynthetic components was observed in LL-HLAF plants, which had the highest photosynthetic nitrogen-use efficiency. Increases in mesophyll thickness and dry mass per unit area governed leaf acclimation in LL-HLBF plants, which tended to have less nitrogen in photosynthetic components and a lower assimilation potential per unit of leaf mass or nitrogen than LL-HLAF plants. The data indicate that the phenological state of seedlings modified the acclimatory response of leaf attributes to increased irradiance. Morphological adaptation of leaves of LL-HLBF plants enhanced photosynthetic capacity per unit leaf area, but not per unit leaf dry mass, whereas substantial redistribution of nitrogen among photosynthetic components in leaves of LL-HLAF plants enhanced both mass- and area-based photosynthetic capacity.

The effect of hydraulic lift on organic matter decomposition, soil nitrogen cycling, and nitrogen acquisition by a grass species.

PubMed

Armas, Cristina; Kim, John H; Bleby, Timothy M; Jackson, Robert B

2012-01-01

Hydraulic lift (HL) is the passive movement of water through plant roots, driven by gradients in water potential. The greater soil-water availability resulting from HL may in principle lead to higher plant nutrient uptake, but the evidence for this hypothesis is not universally supported by current experiments. We grew a grass species common in North America in two-layer pots with three treatments: (1) the lower layer watered, the upper one unwatered (HL), (2) both layers watered (W), and (3) the lower layer watered, the upper one unwatered, but with continuous light 24 h a day to limit HL (no-HL). We inserted ingrowth cores filled with enriched-nitrogen organic matter ((15)N-OM) in the upper layer and tested whether decomposition, mineralization and uptake of (15)N were higher in plants performing HL than in plants without HL. Soils in the upper layer were significantly wetter in the HL treatment than in the no-HL treatment. Decomposition rates were similar in the W and HL treatments and lower in no-HL. On average, the concentration of NH(4)(+)-N in ingrowth cores was highest in the W treatment, and NO(3)(-)-N concentrations were highest in the no-HL treatment, with HL having intermediate values for both, suggesting differential mineralization of organic N among treatments. Aboveground biomass, leaf (15)N contents and the (15)N uptake in aboveground tissues were higher in W and HL than in no-HL, indicating higher nutrient uptake and improved N status of plants performing HL. However, there were no differences in total root nitrogen content or (15)N uptake by roots, indicating that HL affected plant allocation of acquired N to photosynthetic tissues. Our evidence for the role of HL in organic matter decomposition and nutrient cycling suggests that HL could have positive effects on plant nutrient dynamics and nutrient turnover.

A hydrazone covalent organic polymer based micro-solid phase extraction for online analysis of trace Sudan dyes in food samples.

PubMed

Zhang, Chengjiang; Li, Gongke; Zhang, Zhuomin

2015-11-06

Covalent organic polymers (COPs) connected by covalent bonds are a new class of porous network materials with large surface area and potential superiority in sample pretreatment. In this study, a new hydrazone linked covalent organic polymer (HL-COP) adsorbent was well-designed and synthesized based on a simple Schiff-base reaction. The condensation of 1,4-phthalaldehyde and 1,3,5-benzenetricarbohydrazide as organic building blocks led to the synthesis of HL-COP with uniform particle size and good adsorption performance. This HL-COP adsorbent with high hydrophobic property and rich stacking π electrons contained abundant phenyl rings and imine (CN) groups throughout the entire molecular framework. The adsorption mechanism was explored and discussed based on π-π affinity, hydrophobic effect, hydrogen bonding and electron-donor-acceptor (EDA) interaction, which contributed to its strong recognition affinity to target compounds. Enrichment factors were 305-757 for six Sudan dyes by HL-COP micro-solid phase extraction (μ-SPE), indicating its remarkable preconcentration ability. Furthermore, the adsorption amounts by HL-COP μ-SPE were 1.0-11.0 folds as those by three commonly used commercial adsorbents. Then, HL-COP was applied as adsorbent of online μ-SPE coupled with high performance liquid chromatography (HPLC) for enrichment and analysis of trace Sudan dyes in food samples with detection limit of 0.03-0.15μg/L. The method was successfully applied for online analysis of chilli powder and sausage samples. Sudan II and Sudan III in one positive chilli powder sample were actually found and determined with concentrations of 8.3 and 6.8μg/kg, respectively. The recoveries of chilli powder and sausage samples were in range of 75.8-108.2% and 73.8-112.6% with relative standard deviations of 1.2-8.5% and 1.9-9.4% (n=5), respectively. The proposed method was accurate, reliable and convenient for the online simultaneous analysis of trace Sudan dyes in food samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Feasibility of 30-day hospital readmission prediction modeling based on health information exchange data.

PubMed

Swain, Matthew J; Kharrazi, Hadi

2015-12-01

Unplanned 30-day hospital readmission account for roughly $17 billion in annual Medicare spending. Many factors contribute to unplanned hospital readmissions and multiple models have been developed over the years to predict them. Most researchers have used insurance claims or administrative data to train and operationalize their Readmission Risk Prediction Models (RRPMs). Some RRPM developers have also used electronic health records data; however, using health informatics exchange data has been uncommon among such predictive models and can be beneficial in its ability to provide real-time alerts to providers at the point of care. We conducted a semi-systematic review of readmission predictive factors published prior to March 2013. Then, we extracted and merged all significant variables listed in those articles for RRPMs. Finally, we matched these variables with common HL7 messages transmitted by a sample of health information exchange organizations (HIO). The semi-systematic review resulted in identification of 32 articles and 297 predictive variables. The mapping of these variables with common HL7 segments resulted in an 89.2% total coverage, with the DG1 (diagnosis) segment having the highest coverage of 39.4%. The PID (patient identification) and OBX (observation results) segments cover 13.9% and 9.1% of the variables. Evaluating the same coverage in three sample HIOs showed data incompleteness. HIOs can utilize HL7 messages to develop unique RRPMs for their stakeholders; however, data completeness of exchanged messages should meet certain thresholds. If data quality standards are met by stakeholders, HIOs would be able to provide real-time RRPMs that not only predict intra-hospital readmissions but also inter-hospital cases. A RRPM derived using HIO data exchanged through may prove to be a useful method to prevent unplanned hospital readmissions. In order for the RRPM derived from HIO data to be effective, hospitals must actively exchange clinical information through the HIO and develop actionable methods that integrate into the workflow of providers to ensure that patients at high-risk for readmission receive the care they need. Copyright © 2015. Published by Elsevier Ireland Ltd.

Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

PubMed Central

Lorusso, Bruno; Falco, Angela; Madeddu, Denise; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Gervasi, Andrea; Rinaldi, Laura; Lagrasta, Costanza; Maselli, Davide; Gnetti, Letizia; Silini, Enrico M.; Quaini, Eugenio; Ampollini, Luca; Carbognani, Paolo; Quaini, Federico

2015-01-01

Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID:26137493

Security architecture for HL/7 message interchange.

PubMed

Chen, T S; Liao, B S; Lin, M G; Gough, T G

2001-01-01

The promotion of quality medical treatment is very important to the healthcare providers as well as to patients. It requires that the medical resources of different hospitals be combined to ensure that medical information is shared and that resources are not wasted. A computer-based patient record is one of the best methods to accomplish the interchange of the patient's clinical data. In our system, the Health Level/Seven (HL/7) format is used for the interchange of the clinical data, as it has been supported by many healthcare providers and become a â standard'. The security of the interchange of clinical data is a serious issue for people using the Internet for data communication. Several international well-developed security algorithms, models and secure policies are adopted in the design of a security handler for an HL/7 architecture. The goal of our system is to combine our security system with the end-to-end communication systems constructed from the HL/7 format to establish a safe delivery channel. A suitable security interchange environment is implemented to address some shortcomings in clinical data interchange. located at the application layer of the ISO/OSI reference model. The medical message components, sub-components, and related types of message event are the primary goals of the HL/7 protocols. The patient management system, the doctor's system for recording his advice, examination and diagnosis as well as any financial management system are all covered by the HL/7 protocols. Healthcare providers and hospitals in Taiwan are very interested in developing the HL/7 protocols as a common standard for clinical data interchange.

Antioxidant & anticancer activities of isatin (1H-indole-2,3-dione), isolated from the flowers of Couroupita guianensis Aubl

PubMed Central

Premanathan, Mariappan; Radhakrishnan, Srinivasan; Kulangiappar, Kumarasamy; Singaravelu, Ganesan; Thirumalaiarasu, Velayutham; Sivakumar, Thangavel; Kathiresan, Kandasamy

2012-01-01

Background & objectives: Derivatives of isatin are known to have cytotoxicity against human carcinoma cell lines. This compound therefore, has a potential to be used as a chemotherapeutic agent against cancer. This study was done to investigate the antioxidant and anticancer activities of isatin, extracted from flower of a folklore medicinal plant Couroupita guianensis against human promylocytic leukemia (HL60) cells. Methods: Active fractions demonstrating anticancer and antioxidant activities were isolated from the extracts of shade-dried flowers of C. guianensis by bioassay guided fractionation. The free radical scavenging activity was determined using lipid peroxidation assay. Cytotoxicity against human promylocytic leukemia HL60 cells was determined by MTT assay. Apoptotic activity was analyzed by DNA fragmentation and flowcytometry. Results: Isatin isolated from the active fraction showed antioxidant activity with the EC50 value of 72.80 μg/ml. It also exhibited cytotoxicity against human promylocytic leukemia HL60 cells in dose-dependant manner with the CC50 value of 2.94 μg/ml. The isatin-treated cells underwent apoptosis and DNA fragmentation. Apoptosis was confirmed by the FACS analysis using FITC-annexin V markers. Interpretation & conclusions: Isatin showed antioxidant activity and was cytotoxic to the HL60 cells due to induction of apoptosis. The isatin can be further evaluated to be used as a prophylactic agent to prevent the free radical-induced cancer and as a chemotherapeutic agent to kill the cancer cells. PMID:23287130

Synthesis, physicochemical studies, embryos toxicity and DNA interaction of some new Iron(II) Schiff base amino acid complexes

NASA Astrophysics Data System (ADS)

Abdel-Rahman, Laila H.; El-Khatib, Rafat M.; Nassr, Lobna A. E.; Abu-Dief, Ahmed M.

2013-05-01

New Fe(II) Schiff base amino acid complexes derived from the condensation of o-hydroxynaphthaldehyde with L-alanine, L-phenylalanine, L-aspartic acid, L-histidine and L-arginine were synthesized and characterized by elemental analysis, IR, electronic spectra, and conductance measurements. The stoichiometry and the stability constants of the complexes were determined spectrophotometrically. The investigated Schiff bases exhibited tridentate coordination mode with the general formulae [Fe(HL)2]·nH2O for all amino acids except L-histidine. But in case of L-histidine, the ligand acts as tetradentate ([FeL(H2O)2]·2H2O), where HL = mono anion and L = dianion of the ligand. The structure of the prepared complexes is suggested to be octahedral. The prepared complexes were tested for their toxicity on chick embryos and found to be safe until a concentration of 100 μg/egg with full embryos formation. The interaction between CT-DNA and the investigated complexes were followed by spectrophotometry and viscosity measurements. It was found that, the prepared complexes bind to DNA via classical intercalative mode and showed a different DNA cleavage activity with the sequence: nhi > nari > nali > nasi > nphali. The thermodynamic Profile of the binding of nphali complex and CT-DNA was constructed by analyzing the experimental data of absorption titration and UV melting studies with the McGhee equation, van't Hoff's equation, and the Gibbs-Helmholtz equation.

Ligational behavior of Schiff bases towards transition metal ion and metalation effect on their antibacterial activity

NASA Astrophysics Data System (ADS)

Devi, Jai; Batra, Nisha; Malhotra, Rajesh

2012-11-01

New Schiff bases pyrazine-2-carboxylicacid (phenyl-pyridin-2-yl-methylene)-hydrazide (Hpch-bp) HL1 and pyrazine-2-carboxylicacid (pyridin-2-ylmethylene)-hydrazide (Hpch-pc) HL2 derived from condensation of pyrazine carboxylic hydrazide (Hpch) with 2-benzoyl pyridine (bp) or pyridine 2-carbaldehyde (pc) and their transition metal complexes of type ML(1-2)2 have been synthesized, where M = Mn(II), Co(II), Ni(II), Cu(II) and Zn(II). Characterization of ligands and their metal complexes was carried out by elemental analysis, conductimetric studies, magnetic susceptibility, spectroscopic techniques (IR, UV-VIS, NMR, ESR, Mass) and thermogravimetric analysis. The physico-chemical studies revealed octahedral geometry or distorted octahedral geometry around metal ion. These azomethine Schiff base ligands acted as tridentate ? coordinating through carbonyl, azomethine and pyridine nitrogen present in the ligand. The thermodynamic and thermal properties of the complexes have been investigated and it was observed on the basis of these studies that thermal stability of complexes follows the order Mn < Zn < Cu < Co < Ni. The ligands and their complexes were tested for in vitro antibacterial activity at different concentrations against bacteria viz. Gram positive Bacillus subtilis, Micrococcus luteus and Gram negative Pseudomonas aeruginosa, Pseudomonas mendocina. A marked enhancement in biocidal activity of the ligands under similar experimental conditions was observed as a consequence of coordination with metal ions. The trend of growth inhibition in the complexes was found to be in the order: Cu > Mn > Ni > Co > Zn.

Moving towards a Comprehensive Approach for Health Literacy Interventions: The Development of a Health Literacy Intervention Model.

PubMed

Geboers, Bas; Reijneveld, Sijmen A; Koot, Jaap A R; de Winter, Andrea F

2018-06-15

Low health literacy (HL) is associated with many negative health outcomes, and is a major challenge in public health and healthcare. Interventions to improve outcomes associated with HL are needed. In this paper, we aim to develop a comprehensive HL intervention model. We used a multimethod approach, consisting of (1) a literature review of articles listed in MEDLINE, presenting HL intervention models, (2) online consultation of international HL experts, and (3) two consensus meetings with members ( n = 36 and 27) of a consortium studying HL among older adults (50+) in Europe. In our literature review, we identified twenty-two HL models, only a few of which focused explicitly on interventions. Sixty-eight health literacy experts took part in the online survey. The results from all three methods came together in a comprehensive HL intervention model. This model conceptualized interventions as potentially targeting five factors affecting HL outcomes: (1) individuals’ personal characteristics, (2) individuals’ social context, (3) communication between individuals and health professionals, (4) health professionals’ HL capacities, and (5) health systems. Our model is the first comprehensive HL model focused specifically on interventions. The model can support the further development of HL interventions to improve the health outcomes of people with low HL.

The Relationship between Exposure to Missiles and PTSD Symptoms as a Function of Hemispheric Preference in Israelis.

PubMed

Herzog, Daniela; Farchi, Moshe; Gidron, Yori

2018-01-01

Recent research proposes that left hemispheric lateralization (HL) may protect against the effects of life events on mental distress. This study extends these findings by examining the protective role of left HL in the relationship between war threat (missile exposure) and PTSD symptoms. A sample of 186 Israelis, exposed to missile attacks, completed brief scales of self-reported missile exposure, a subjective and a neuropsychological HL measure, and of PTSD symptoms. The sample was split into right HL and left HL individuals on both HL measures. Self-reported missile exposure was positively associated with PTSD symptoms in right HL, but not in left HL individuals on both HL measures. These results replicate, extend our previous results and suggest that left HL may even protect against the effects of severe life threatening events. Results are discussed in relation to neuropsychological and neurophysiological differences between the hemispheres.

Potent in vitro anticancer activity of metacycloprodigiosin and undecylprodigiosin from a sponge-derived actinomycete Saccharopolyspora sp. nov.

PubMed

Liu, Rui; Cui, Cheng-Bin; Duan, Lin; Gu, Qian-Qun; Zhu, Wei-Ming

2005-12-01

Bioassay-guided fractionation of CHCl3 extract from the fermentation broth of a sponge Mycale plumose-derived actinomycete Saccharopolyspora sp. nov., led to the isolation of two known prodigiosin analogs--metacycloprodigiosin (1) and undecylprodigiosin (2). These compounds exhibited significant cytotoxic activities against five cancer cell lines: P388, HL60, A-549, BEL-7402, and SPCA4. This is the first report on the significant cytotoxicity of metacycloprodigiosin (1) against human cancer cell lines.

Standardizing intensive care device data to enable secondary usages.

PubMed

Ingenerf, Josef; Kock, Ann-Kristin; Poelker, Marcel; Seidl, Konrad; Zeplin, Georg; Mersmann, Stefan; Handels, Heinz

2012-01-01

To represent medical device observations in a format that is consumable by clinical software, standards like HL7v3 and ISO/IEEE 11073 should be used jointly. This is demonstrated in a project with Dräger Medical GmbH focusing on their Patient Data Management System (PDMS) in intensive care, called Integrated Care Manager (ICM). Patient and device data of interest should be mapped to suitable formats to enable data exchange and decision support. Instead of mapping device data to target formats bilaterally we use a generic HL7v3 Refined Message Information Model (RMIM) with device specific parts adapted to ISO/IEEE 11073 DIM. The generality of the underlying model (based on Yuksel et al. [1]) allows the flexible inclusion of IEEE 11073 conformant device models of interest on the one hand and the generation of needed artifacts for secondary usages on the other hand, e.g. HL7 V2 messages, HL7 CDA documents like the Personal Health Monitoring Report (PHMR) or web services. Hence, once the medical device data are obtained in the RMIM format, it can quite easily be transformed into HL7-based standard interfaces through XSL transformations because these interfaces all have their building blocks from the same RIM. From there data can be accessed uniformly, e.g. as needed by Dräger´s decision support system SmartCare [2] for automated control and optimization of weaning from mechanical ventilation.

The Use and Role of Pop Culture in Heritage Language Learning: A Study of Advanced Learners of Korean

ERIC Educational Resources Information Center

Choi, Jayoung; Yi, Youngjoo

2012-01-01

Despite the important use of pop culture in many instructional settings, its use in the heritage language (HL) classroom remains largely unexplored. Thus, this article reports findings from classroom-based qualitative research that examined the use and role of pop culture in advanced Korean HL learners' literacy engagement and identity…

Synthesis, structural characterization, fluorescence, antimicrobial, antioxidant and DNA cleavage studies of Cu(II) complexes of formyl chromone Schiff bases.

PubMed

Kavitha, P; Saritha, M; Laxma Reddy, K

2013-02-01

Cu(II) complexes have been synthesized from different Schiff bases, such as 3-((2-hydroxy phenylimino)methyl)-4H-chromen-4-one (HL(1)), 2-((4-oxo-4H-chromen-3-yl)methylneamino) benzoicacid (HL(2)), 3-((3-hydroxypyridin-2-ylimino)methyl)-4H-chromen-4-one (HL(3)) and 3-((2-mercaptophenylimino)methyl)-4H-chromen-4-one (HL(4)). The complexes were characterized by analytical, molar conductance, IR, electronic, magnetic, ESR, thermal, powder XRD and SEM studies. The analytical data reveal that metal to ligand molar ratio is 1:2 in all the complexes. Molar conductivity data indicates that all the Cu(II) complexes are neutral. On the basis of magnetic and electronic spectral data, distorted octahedral geometry is proposed for all the Cu(II) complexes. Thermal behaviour of the synthesized complexes illustrates the presence of lattice water molecules in the complexes. X-ray diffraction studies reveal that all the ligands and their Cu(II) complexes have triclinic system with different unit cell parameters. Antimicrobial, antioxidant and DNA cleavage activities indicate that metal complexes exhibited greater activity as compared with ligands. Copyright © 2012 Elsevier B.V. All rights reserved.

Dose- and Time-Dependent Response of Human Leukemia (HL-60) Cells to Arsenic Trioxide Treatment

PubMed Central

Yedjou, Clement G.; Moore, Pamela; Tchounwou, Paul B.

2006-01-01

The treatment of acute promyelocytic leukemia (APL) has been based on the administration of all-trans retinoic acid plus anthracycline chemotherapy, which is very effective as first line therapy; however 25 to 30% of patients will relapse with their disease becoming refractory to conventional therapy. Recently, studies have shown arsenic trioxide to be effective in the treatment of acute promyelocytic leukemia. In this study, we used the human leukemia (HL-60) cell line as a model to evaluate the cytoxicity of arsenic trioxide based on the MTT assay. Data obtained from this assay indicated that arsenic trioxide significantly reduced the viability of HL-60 cells, showing LD50 values of 14.26 ± 0.5μg/mL, 12.54 ± 0.3μg/mL, and 6.4 ± 0.6μg/mL upon 6, 12, and 24 hours of exposure, respectively; indicating a dose- and time-dependent response relationship. Findings from the present study indicate that arsenic trioxide is highly cytotoxic to human leukemia (HL-60) cells, supporting its use as an effective therapeutic agent in the management of acute promyelocytic leukemia. PMID:16823087

The effects of feeding rations that differ in fiber and fermentable starch within a day on milk production and the daily rhythm of feed intake and plasma hormones and metabolites in dairy cows.

PubMed

Niu, M; Ying, Y; Bartell, P A; Harvatine, K J

2017-01-01

A daily pattern of feed intake, milk synthesis, and plasma metabolites and hormones occurs in dairy cows fed a total mixed ration once or twice a day. The objective of this study was to determine if feeding multiple rations within a day, complementing these rhythms, would improve milk production. Twelve Holstein cows were used in a replicated 3×3 Latin square design with 21-d periods. Cows were housed in tie stalls with feed tubs, and feed weight was recorded every 10 s for observation of feeding behavior. Rations were a low fiber and high fermentable starch ration [LFHS; 27.4% neutral detergent fiber (NDF) and 31.7% starch based on 55.7% corn silage and 14.1% steam-flaked corn], a high fiber and low fermentable starch ration (HFLS; 31.7% NDF and 22.3% starch based on 44% corn silage, 26.3% alfalfa haylage, and no steam-flaked corn), and a total mixed ration that was a 1:3 ratio of LFHS and HFLS (30.7% NDF, 24.5% starch). The control treatment (CON) cows were fed the total mixed ration at 0700h, the high/low treatment (HL) fed HFLS ration at 0700h and LFHS ration at 2200h, and the low/high (LH) treatment fed LFHS ration at 0700h and HFLS ration at 1100h (LFHS and HFLS rations fed at a 1:3 ratio). No effect was found of treatment on daily milk, but LH decreased milk fat concentration and yield compared with HL (0.2 percentage units and 0.24kg, respectively). Daily dry matter and NDF intake and total-tract digestibility did not differ between treatments. The HL treatment reduced intake at the morning-conditioned meal after feeding and reduced intake before the evening feeding. A treatment by time of day interaction was found for fecal NDF and indigestible NDF concentration, blood urea nitrogen (BUN), plasma insulin, and fatty acid concentration, and body temperature. The CON and LH treatments increased the daily amplitude of fecal NDF by 1.0 and 1.1 percentage units compared with HL. Plasma insulin was higher in HL than CON at 0100 and 0400h, but lower at 1300 and 1900h. Plasma fatty acids were higher for CON than HL at 0700h and HL was lower than LH at 0400 and 1900h. Plasma BUN was higher for HL than control at 0100h, but lower at 1000h. Body temperature in CON and HL treatments followed a similar diurnal pattern, whereas body temperature for LH was lower than that of HL treatment at 1300 and 2300h. No daily rhythm was found of fecal indigestible NDF concentration, plasma glucose, or fatty acids detected in the HL treatment, and the amplitude of plasma insulin and BUN was lower for HL compared with CON (70 and 60% decrease, respectively). In conclusion, feeding 2 rations that differ in fiber and fermentable starch modifies diurnal rhythms in dairy cows. Furthermore, feeding a high fiber and low fermentable starch ration during the high intake period of the day may stabilize nutrient absorption across the day. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Synthesis, characterization and antitumor activity of Ln(III) complexes with hydrazone Schiff base derived from 2-acetylpyridine and isonicotinohydrazone

PubMed Central

Xie, Jing; Shen, Shanshan; Chen, Ruhua; Xu, Jun; Dong, Kun; Huang, Jiancui; Lu, Qin; Zhu, Wenjiao; Ma, Tieliang; Jia, Lei; Cai, Hongxin; Zhu, Taofeng

2017-01-01

In the present study, two isostructural lanthanide (Ln)(III) complexes, namely Ln(HL)2(NO3)(CH3OH)2)·CH3OH, where Ln = La in complex 1 and Ce in complex 2, and hydrogen ligand (HL) = (E)-N'-[1-(2-pyridinyl)ethylidene]isonicotinohydrazone, have been isolated and characterized by elemental analysis, infrared spectra and single-crystal X-ray diffraction analysis. The results revealed that the acylhydrazone ligand HL in each complex was deprotonated as an anionic ligand and coordinated to the central La(III) ion via enolization of oxygen and nitrogen atoms. Furthermore, the antitumor effects and potential mechanisms of the two complexes were explored in the human lung cancer cell line A549 and in the human gastric cancer cell lines BGC823 and SGC7901. In the present study, the roles the two complexes on the proliferation and apoptosis of the above tumor cell lines were determined by MTT assay and Annexin V/propidium iodide flow cytometry, respectively. Furthermore, various apoptosis-associated key genes, including caspase 3, B cell lymphoma (Bcl)-2-associated X protein (Bax) and Bcl-2, were detected by western blotting to explore the possible antitumor mechanisms of the two complexes. The results revealed that the two complexes had comparable antitumor activities in terms of inhibiting proliferation and inducing apoptosis in tumor cell lines. The changes in the protein expression levels of caspase 3, Bax and Bcl-2 further verified the apoptosis-promoting mechanisms of the two complexes in tumor cell lines. These findings have a great potential in biomedical applications of novel Ln(III) complexes. PMID:28599443

Effects of highly ripened cheeses on HL-60 human leukemia cells: antiproliferative activity and induction of apoptotic DNA damage.

PubMed

Yasuda, S; Ohkura, N; Suzuki, K; Yamasaki, M; Nishiyama, K; Kobayashi, H; Hoshi, Y; Kadooka, Y; Igoshi, K

2010-04-01

To establish cheese as a dairy product with health benefits, we examined the multifunctional role of cheeses. In this report, we clarify whether different types of commercial cheeses may possess antiproliferative activity using HL-60 human promyelocytic leukemia cell lines as a cancer model. Among 12 cheese extracts tested, 6 (Montagnard, Pont-l'Eveque, Brie, Camembert, Danablue, and Blue) revealed strong growth inhibition activity and induction of DNA fragmentation in HL-60 cells. Based on the quantification of nitrogen contents in different cheese samples, a positive correlation between the ripeness of various cheeses and their antiproliferative activity tested in HL-60 cells was displayed. Four varieties of Blue cheese ripened for 0, 1, 2, or 3 mo demonstrated that the Blue cheese ripened for a long term was capable of causing the strong suppression of the cell growth and the induction of apoptotic DNA damage as well as nucleic morphological change in HL-60 cells. Collectively, these results obtained suggest a potential role of highly ripened cheeses in the prevention of leukemic cell proliferation. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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.

Health literacy and health: rethinking the strategies for universal health coverage in Ghana.

PubMed

Amoah, Padmore Adusei; Phillips, David R

2018-06-01

Health literacy (HL) is generally thought to be associated with positive health behaviour, appropriate health service utilisation and acceptance of interventions to maximise health outcomes. It is, therefore, increasingly suggested that evidence-based research should investigate how HL may operate in the context of universal health coverage (UHC). However, the role of HL in the relationships between elements of UHC such as access to health care and health insurance has not been widely explored. This applies in particular in Sub-Saharan Africa, although service coverage and health outcomes vary hugely between and within many countries. This article addresses this lacuna in Ghana, today one of the Africa's most promising health systems. It is a cross-sectional study. The study used structured interviews to gather data from 779 rural and urban adults using a multistage cluster sampling approach. In a three-step multiple hierarchical linear regression model, HL (B = -.09, standard error [SE] = .04) and health insurance subscription (B = -.15, SE = .04) were found to be inversely associated with poor health-related quality of life (HRQoL). Access to health care did not predict HRQoL (B = -.02, SE = .02). However, the interaction between access to health care and HL produced a negative effect on poor HRQoL (B = -.08, SE = .03). The interaction between HL and health insurance subscription also showed a similar effect on HRQoL (B = -.10, SE = .03). Further analysis depicted that access to health care (β = -.09, P = .05) and health insurance subscription (β = -.24, P = .00) related positively to HRQoL only when HL was high. The article argues that where HL is low, even favourable policies for UHC are likely to miss set targets. While not losing sight of relevant sociocultural elements, enhancing HL should be a central strategy for policies aimed at bridging health inequalities and improving UHC. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Synthesis, characterization and biological approach of metal chelates of some first row transition metal ions with halogenated bidentate coumarin Schiff bases containing N and O donor atoms.

PubMed

Prabhakara, Chetan T; Patil, Sangamesh A; Toragalmath, Shivakumar S; Kinnal, Shivashankar M; Badami, Prema S

2016-04-01

The impregnation of halogen atoms in a molecule is an emerging trend in pharmaceutical chemistry. The presence of halogens (Cl, Br, I and F) increases the lipophilic nature of molecule and improves the penetration of lipid membrane. The presence of electronegative halogen atoms increases the bio- activity of core moiety. In the present study, Co(II), Ni(II) and Cu(II) complexes are synthesised using Schiff bases (HL(I) and HL(II)), derived from 8-formyl-7-hydroxy-4-methylcoumarin/3-chloro-8-formyl-7-hydroxy-4-methylcoumarin with 2,4-difluoroaniline/o-toluidine respectively. The synthesized compounds were characterized by spectral (IR, NMR, UV-visible, Mass, ESI-MS, ESR), thermal, fluorescence and molar conductivity studies. All the synthesized metal complexes are completely soluble in DMF and DMSO. The non-electrolytic nature of the metal complexes was confirmed by molar conductance studies. Elemental analysis study suggest [ML2(H2O)2] stoichiometry, here M=Co(II), Ni(II) and Cu(II), L=deprotonated ligand. The obtained IR data supports the binding of metal ion to Schiff base. Thermal study suggests the presence of coordinated water molecules. Electronic spectral results reveal six coordinated geometry for the synthesized metal complexes. The Schiff bases and their metal complexes were evaluated for antibacterial (Pseudomonas aureginosa and Proteus mirabilis), antifungal (Aspergillus niger and Rhizopus oryzae), anthelmintic (Pheretima posthuma) and DNA cleavage (Calf Thymus DNA) activities. Copyright © 2016 Elsevier B.V. All rights reserved.

Spectroscopic, thermal, catalytic and biological studies of Cu(II) azo dye complexes

NASA Astrophysics Data System (ADS)

El-Sonbati, A. Z.; Diab, M. A.; El-Bindary, A. A.; Shoair, A. F.; Hussein, M. A.; El-Boz, R. A.

2017-08-01

New complexes of copper(II) with azo compounds of 5-amino-2-(aryl diazenyl)phenol (HLn) are prepared and investigated by elemental analyses, molar conductance, IR, 1H NMR, UV-Visible, mass, ESR spectra, magnetic susceptibility measurements and thermal analyses. The complexes have a square planar structure and general formula [Cu(Ln)(OAc)]H2O. Study the catalytic activities of Cu(II) complexes toward oxidation of benzyl alcohol derivatives to carbonyl compounds were tested using H2O2 as the oxidant. The intrinsic binding constants (Kb) of the ligands (HLn) and Cu(II) complexes (1-4) with CT-DNA are determined. The formed compounds have been tested for biological activity of antioxidants, antibacterial against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and yeast Candida albicans. Antibiotic (Ampicillin) and antifungal against (Colitrimazole) and cytotoxic compounds HL1, HL2, HL3 and complex (1) showed moderate to good activity against S. aureus, E. coli and Candida albicans, and also to be moderate on antioxidants and toxic substances. Molecular docking is used to predict the binding between the ligands with the receptor of breast cancer (2a91).

[Effect of acoustic stimulus intensity on air-conducted sound elicited ocular vestibular-evoked myogenic potential and cervical vestibular-evoked myogenic potential].

PubMed

Zhang, Rui; Xu, Min; Zhang, Qing; Yang, Yin-Tong; Chen, Yanfei

2014-06-01

To observe the effect of acoustic stimulus intensity on air-conducted sound elicited ocular vestibular- evoked myogenic potential (oVEMP) and cervical vestibular-evoked myogenic potential (cVEMP) in normal young Chinese subjects. Thirty-five normal subjects aged 4-40 years (20.80∓8.89 years), including 16 males and 19 females, were recruited for conventional oVEMP and cVEMP examinations. The responses obtained from each side using 500 Hz tone bursts were divided into 6 groups according to different sound intensities (100, 95, 90, 85, 80 and 75dB nHL). The response rate and normal parameters of each stimulus intensity group were calculated. As the acoustic stimulus intensity decreased, the oVEMP response rate decreased from 100% in both 100 dB nHL and 95dB nHL groups to 97.14% (90 dB nHL), 54.29% (85 dB nHL), 14.29% (80 dB nHL), and 2.86% (75 dB nHL), and the response rate of cVEMP, 100% in both 100 dB nHL and 95dB nHL groups, was lowered to 97.14% (90 dB nHL), 84.29% (85 dB nHL), 38.57% (80 dB nHL) and 8.57% (75 dB nHL). The response rate and the parameters were comparable between 100 and 95 dB nHL groups. As the acoustic stimulus intensity decreases, both oVEMP and cVEMP show decreased response rate and amplitude. For Chinese subjects under 40 years of age, we recommend 95dB nHL as the maximum initial stimulus intensity in VEMPs test.

Different composition and distribution patterns of mineral-protected versus hydrolyzable lipids in shrubland soils

NASA Astrophysics Data System (ADS)

Cai, Yue; Tang, Zhiyao; Xiong, Gaoming; Xie, Zongqiang; Liu, Zongguang; Feng, Xiaojuan

2017-09-01

Mineral protection is known as an important mechanism stabilizing soil organic carbon (SOC). However, the composition, sources, and variations of mineral-protected SOC remain poorly constrained. To fill this knowledge gap, we used hydrofluoric acid to demineralize soil matrix and compared the sources and distribution of mineral-protected lipids (ML) versus hydrolyzable lipids (HL) of four typical Chinese shrubland soils. ML was found to represent a sizable fraction (9-32%) of total aliphatic lipids (including n-alkanols; n-alkanoic acids; α,ω-alkanedioic acids; hydroxyalkanoic acids; and midchain-substituted acids) in all soils. Based on carbon chain length and branch positions, microbe- and plant-derived lipids were distinguished. No significant difference was found in the ratio of microbe- to plant-derived lipids in ML versus HL, implying that plant and microbial inputs are equally important for the mineral-associated soil lipids. However, ML contained a higher proportion of nonspecific lipids, especially at depths. Furthermore, to evaluate key environmental variable(s) controlling the distribution of different lipid components, a multiple stepwise regression analysis was conducted. Notably, ML was mainly affected by SOC-to-nitrogen ratio instead of mineralogical properties, implying that the accrual of mineral-associated soil lipids relies strongly on organic matter properties. Collectively, our findings provide novel insights on sources and accumulation mechanisms of mineral-protected soil lipids. SOC decomposition and subsequent accretion of degradation products appear to be vital for the sequestration of mineral-associated soil lipids and warrant better recognition in the investigations of stable soil carbon accumulation mechanisms.

Nondeducibility-Based Analysis of Cyber-Physical Systems

NASA Astrophysics Data System (ADS)

Gamage, Thoshitha; McMillin, Bruce

Controlling information flow in a cyber-physical system (CPS) is challenging because cyber domain decisions and actions manifest themselves as visible changes in the physical domain. This paper presents a nondeducibility-based observability analysis for CPSs. In many CPSs, the capacity of a low-level (LL) observer to deduce high-level (HL) actions ranges from limited to none. However, a collaborative set of observers strategically located in a network may be able to deduce all the HL actions. This paper models a distributed power electronics control device network using a simple DC circuit in order to understand the effect of multiple observers in a CPS. The analysis reveals that the number of observers required to deduce all the HL actions in a system increases linearly with the number of configurable units. A simple definition of nondeducibility based on the uniqueness of low-level projections is also presented. This definition is used to show that a system with two security domain levels could be considered “nondeducibility secure” if no unique LL projections exist.

Prototype of a Standards-Based EHR and Genetic Test Reporting Tool Coupled with HL7-Compliant Infobuttons

PubMed Central

Crump, Jacob K.; Del Fiol, Guilherme; Williams, Marc S.; Freimuth, Robert R.

2018-01-01

Integration of genetic information is becoming increasingly important in clinical practice. However, genetic information is often ambiguous and difficult to understand, and clinicians have reported low-self-efficacy in integrating genetics into their care routine. The Health Level Seven (HL7) Infobutton standard helps to integrate online knowledge resources within Electronic Health Records (EHRs) and is required for EHR certification in the US. We implemented a prototype of a standards-based genetic reporting application coupled with infobuttons leveraging the Infobutton and Fast Healthcare Interoperability Resources (FHIR) Standards. Infobutton capabilities were provided by Open Infobutton, an open source package compliant with the HL7 Infobutton Standard. The resulting prototype demonstrates how standards-based reporting of genetic results, coupled with curated knowledge resources, can provide dynamic access to clinical knowledge on demand at the point of care. The proposed functionality can be enabled within any EHR system that has been certified through the US Meaningful Use program.

Cytotoxic Effects of Dimorfolido-N-Trichloroacetylphosphorylamide and Dimorfolido-N-Benzoylphosphorylamide in Combination with C60 Fullerene on Leukemic Cells and Docking Study of Their Interaction with DNA.

PubMed

Prylutska, S; Grynyuk, I; Grebinyk, A; Hurmach, V; Shatrava, Iu; Sliva, T; Amirkhanov, V; Prylutskyy, Yu; Matyshevska, O; Slobodyanik, M; Frohme, M; Ritter, U

2017-12-01

Dimorfolido-N-trichloroacetylphosphorylamide (HL1) and dimorfolido-N-benzoylphosphorylamide (HL2) as representatives of carbacylamidophosphates were synthesized and identified by the methods of IR, 1 H, and 31 P NMR spectroscopy. In vitro HL1 and HL2 at 1 mM concentration caused cell specific and time-dependent decrease of leukemic cell viability. Compounds caused the similar gradual decrease of Jurkat cells viability at 72 h (by 35%). HL1 had earlier and more profound toxic effect as compared to HL2 regardless on leukemic cell line. Viability of Molt-16 and CCRF-CEM cells under the action of HL1 was decreased at 24 h (by 32 and 45%, respectively) with no substantial further reducing up to 72 h. Toxic effect of HL2 was detected only at 72 h of incubation of Jurkat and Molt-16 cells (cell viability was decreased by 40 and 45%, respectively).It was shown that C 60 fullerene enhanced the toxic effect of HL2 on leukemic cells. Viability of Jurkat and CCRF-CEM cells at combined action of C 60 fullerene and HL2 was decreased at 72 h (by 20 and 24%, respectively) in comparison with the effect of HL2 taken separately.In silico study showed that HL1 and HL2 can interact with DNA and form complexes with DNA both separately and in combination with C 60 fullerene. More stable complexes are formed when DNA interacts with HL1 or C 60  + HL2 structure. Strong stacking interactions can be formed between HL2 and C 60 fullerene. Differences in the types of identified bonds and ways of binding can determine distinction in cytotoxic effects of studied compounds.

Epidemiology and Long-term Clinical and Biologic Risk Factors for Pneumonia in Community-Dwelling Older Americans

PubMed Central

Alvarez, Karina; Loehr, Laura; Folsom, Aaron R.; Newman, Anne B.; Weissfeld, Lisa A.; Wunderink, Richard G.; Kritchevsky, Stephen B.; Mukamal, Kenneth J.; London, Stephanie J.; Harris, Tamara B.; Bauer, Doug C.; Angus, Derek C.

2013-01-01

Background: Preventing pneumonia requires better understanding of incidence, mortality, and long-term clinical and biologic risk factors, particularly in younger individuals. Methods: This was a cohort study in three population-based cohorts of community-dwelling individuals. A derivation cohort (n = 16,260) was used to determine incidence and survival and develop a risk prediction model. The prediction model was validated in two cohorts (n = 8,495). The primary outcome was 10-year risk of pneumonia hospitalization. Results: The crude and age-adjusted incidences of pneumonia were 6.71 and 9.43 cases/1,000 person-years (10-year risk was 6.15%). The 30-day and 1-year mortality were 16.5% and 31.5%. Although age was the most important risk factor (range of crude incidence rates, 1.69-39.13 cases/1,000 person-years for each 5-year increment from 45-85 years), 38% of pneumonia cases occurred in adults < 65 years of age. The 30-day and 1-year mortality were 12.5% and 25.7% in those < 65 years of age. Although most comorbidities were associated with higher risk of pneumonia, reduced lung function was the most important risk factor (relative risk = 6.61 for severe reduction based on FEV1 by spirometry). A clinical risk prediction model based on age, smoking, and lung function predicted 10-year risk (area under curve [AUC] = 0.77 and Hosmer-Lemeshow [HL] C statistic = 0.12). Model discrimination and calibration were similar in the internal validation cohort (AUC = 0.77; HL C statistic, 0.65) but lower in the external validation cohort (AUC = 0.62; HL C statistic, 0.45). The model also calibrated well in blacks and younger adults. C-reactive protein and IL-6 were associated with higher pneumonia risk but did not improve model performance. Conclusions: Pneumonia hospitalization is common and associated with high mortality, even in younger healthy adults. Long-term risk of pneumonia can be predicted in community-dwelling adults with a simple clinical risk prediction model. PMID:23744106

Impact of treatment and insurance on socioeconomic disparities in survival after adolescent and young adult Hodgkin lymphoma: A population-based study

PubMed Central

Keegan, Theresa H.M.; DeRouen, Mindy C.; Parsons, Helen M.; Clarke, Christina A.; Goldberg, Debbie; Flowers, Christopher R.; Glaser, Sally L.

2015-01-01

Background Previous studies documented racial/ethnic and socioeconomic disparities in survival after Hodgkin lymphoma (HL) among adolescents and young adults (AYAs), but did not consider the influence of combined-modality treatment and health insurance. Methods Data for 9,353 AYA patients aged 15–39 when diagnosed with HL during 1988–2011 were obtained from the California Cancer Registry. Using multivariate Cox proportional hazards regression, we examined the impact of socio-demographic characteristics (race/ethnicity, neighborhood socioeconomic status (SES), and health insurance), initial combined-modality treatment, and subsequent cancers on survival. Results Over the 24-year study period, we observed improvements in HL-specific survival by diagnostic period and differences in survival by race/ethnicity, neighborhood SES and health insurance for a subset of more recently diagnosed patients (2001–2011). In multivariable analyses, HL-specific survival was worse for Blacks than Whites with early-stage (Hazard Ratio (HR): 1.68; 95% Confidence Interval (CI): 1.14, 2.49) and late-stage disease (HR: 1.68; 95% CI: 1.17, 2.41) and for Hispanics than Whites with late-stage disease (HR: 1.58; 95% CI: 1.22, 2.04). AYAs diagnosed with early-stage disease experienced worse survival if they also resided in lower SES neighborhoods (HR: 2.06; 95% CI: 1.59, 2.68). Furthermore, more recently diagnosed AYAs with public health insurance or who were uninsured experienced worse HL-specific survival (HR: 2.08; 95% CI: 1.52, 2.84). Conclusion Our findings identify several subgroups of HL patients at higher risk for HL mortality. Impact Identifying and reducing barriers to recommended treatment and surveillance in these AYAs at much higher risk of mortality is essential to ameliorating these survival disparities. PMID:26826029

Realization of Real-Time Clinical Data Integration Using Advanced Database Technology

PubMed Central

Yoo, Sooyoung; Kim, Boyoung; Park, Heekyong; Choi, Jinwook; Chun, Jonghoon

2003-01-01

As information & communication technologies have advanced, interest in mobile health care systems has grown. In order to obtain information seamlessly from distributed and fragmented clinical data from heterogeneous institutions, we need solutions that integrate data. In this article, we introduce a method for information integration based on real-time message communication using trigger and advanced database technologies. Messages were devised to conform to HL7, a standard for electronic data exchange in healthcare environments. The HL7 based system provides us with an integrated environment in which we are able to manage the complexities of medical data. We developed this message communication interface to generate and parse HL7 messages automatically from the database point of view. We discuss how easily real time data exchange is performed in the clinical information system, given the requirement for minimum loading of the database system. PMID:14728271

Identification of three protein disulfide isomerase members from Haemaphysalis longicornis tick.

PubMed

Liao, Min; Hatta, Takeshi; Umemiya, Rika; Huang, Penglong; Jia, Honglin; Gong, Haiyan; Zhou, Jinlin; Nishikawa, Yoshifumi; Xuan, Xuenan; Fujisaki, Kozo

2007-07-01

Three genes encoding putative protein disulfide isomerase (PDI) were isolated from the Haemaphysalis longicornis EST database and designed as HlPDI-1, HlPDI-2, and HlPDI-3. All three PDI genes contain two typical PDI active sites CXXC and encode putative 435, 499, and 488 amino acids, respectively. The recombinant proteins expressed in Escherichia coli all show PDI activities, and the activities were inhibited by a PDI-specific inhibitor, zinc bacitracin. Western blot analysis and real-time PCR revealed that three HlPDIs were present in all the developmental stages of the tick as well as in the midgut, salivary glands, ovary, hemolymph, and fatbody of adult female ticks, but the three genes were expressed at the highest level in the egg stage. HlPDI-1 is expressed primarily in the ovary and secondarily in the salivary glands. HlPDI-2 and HlPDI-3 are expressed primarily in the salivary gland, suggesting that the PDI genes are important for tick biology, especially for egg development, and that they play distinct roles in different tissues. Blood feeding induced significantly increased expression of HlPDI-1 and HlPDI-3 in both partially fed nymphs and adults. Babesia gibsoni-infected larval ticks expressed HlPDI-1 and HlPDI-3 2.0 and 4.0 times higher than uninfected normal larval ticks, respectively. The results indicate that HlPDI-1 and HlPDI-3 might be involved in tick blood feeding and Babesia parasite infection in ticks.

Exploring the DNA binding/cleavage, cellular accumulation and topoisomerase inhibition of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases and their platinum(II) complexes.

PubMed

Neves, Amanda P; Pereira, Michelle X G; Peterson, Erica J; Kipping, Ralph; Vargas, Maria D; Silva, Floriano P; Carneiro, J Walkimar M; Farrell, Nicholas P

2013-02-01

Several chlorido and amino Pt(2+) complexes of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases HL exhibiting moderate to high cytotoxicity against cancer cell lines were studied in order to investigate their modes of DNA binding, in vitro DNA strand breaks, mechanism of topoisomerase (Topo I) inhibition and cellular accumulation. DNA model base studies have shown that complex 1a [Pt(HL1)Cl(2)] was capable of binding covalently to 9-ethylguanine (9-EtG) and 5'-GMP. (1)H NMR and mass spectrometry studies have shown that both chlorides were substituted by 9-EtG ligands, whereas 5'-GMP was able to replace only one chlorido ligand, due to steric hindrance. The chlorido Pt(2+) complexes [Pt(HL)Cl(2)] highly accumulate in prostate (PC-3) and melanoma (MDA-MB-435) cell lines, being able to induce DNA strand breaks in vitro and inhibit Topo I by a catalytic mode. On the other hand, the free 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones HL and the amino Pt(2+) complexes [Pt(L(-))(NH(3))(2)]NO(3) neither cause DNA strand breakage nor exhibit strong DNA interaction, nevertheless the latter were also found to be catalytic inhibitors of Topo I at 100μM. Thus, coordination of the Mannich bases HL to the "PtCl(2)" fragment substantially affects the chemical and biophysical properties of the pro-ligands, leading to an improvement of their DNA binding properties and generating compounds that cleave DNA and catalytically inhibit Topo I. Finally, the high cytotoxicity exhibited by the free (uncomplexed) 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones might be associated with their decomposition in solution, which is not observed for the Pt(2+) complexes. Copyright © 2012 Elsevier Inc. All rights reserved.

Syntheses, crystallographic, mass-spectroscopic determination and antioxidant studies of Co(II), Ni(II) and Cu(II) complexes of a new imidazol based Schiff base.

PubMed

Demir, Serkan; Güder, Aytaç; Yazıcılar, Turan K; Çağlar, Sema; Büyükgüngör, Orhan

2015-01-01

A new imidazole-based Schiff base, 2-((1H-imidazol-4-yl)methyleneamino)benzylalcohol (HL) and corresponding analogous bis(2-((1H-imidazol-4-yl)methyleneimino)benzylalcohol)metal(II) perchlorates (M: Co(1), Ni(2), Cu(3)) have prepared and characterized by elemental analyses, ESI-MS, IR, UV-Vis spectroscopies and conductivity measurements. X-ray single crystal structures of 1 and 2 have been also determined. Elemental analyses, spectroscopic and conductance data of 3 demonstrated similar structural features with these of crystallographically characterized complexes and based upon this relevances, HL ligands are neutrally coordinated to metal(II) ions in tridentate mode and all complexes are isostructural, dicathionic, contain perchlorate anions as complementary ions and, are in octahedral geometry with the formulae of [M(HL)2](ClO4)2 (for 3) and [M(HL)2](ClO4)2·H2O (for 1 and 2). Radical scavenging activities of the complexes have been evaluated by using DPPH, DMPD(+), and ABTS(+) assays. SC50 values (μg/mL) of the complexes and standards on DPPH, DMPD(+), ABTS(+) follow the sequences, BHA (9.06±0.33)>CMPD3 (15.62±0.52)>CMPD2 (17.43±0.29)>Rutin (21.65±0.60)>CMPD1 (25.67±0.51)>Trolox (28.57±0.37), Rutin>BHA>CMPD3>CMPD2>Trolox>CMPD1, and Trolox>BHA>CMPD3>CMPD2>Rutin>CMPD1 respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL.

PubMed

Pilichowska, Monika; Pittaluga, Stefania; Ferry, Judith A; Hemminger, Jessica; Chang, Hong; Kanakry, Jennifer A; Sehn, Laurie H; Feldman, Tatyana; Abramson, Jeremy S; Kritharis, Athena; Hernandez-Ilizaliturri, Francisco J; Lossos, Izidore S; Press, Oliver W; Fenske, Timothy S; Friedberg, Jonathan W; Vose, Julie M; Blum, Kristie A; Jagadeesh, Deepa; Woda, Bruce; Gupta, Gaurav K; Gascoyne, Randy D; Jaffe, Elaine S; Evens, Andrew M

2017-12-12

Gray zone lymphoma (GZL) is described as sharing features with classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 North American academic centers were evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universal B-cell derivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20 + , 83%; PAX5 + , 100%; BCL6 + , 20%; MUM1 + , 100%; CD30 + , 92%; EBV + , 4%). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n = 27 (including n = 10 NS grade 2); lymphocyte predominant HL, n = 4; DLBCL, n = 4; EBV + DLBCL, n = 3; primary mediastinal large BCL n = 2; lymphocyte-rich cHL and BCL-not otherwise specified, n = 1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69% vs 41%; P = .038) and less likely more than 1 extranodal site (0% vs 25%; P = .019). With a 44-month median follow-up, 3-year progression-free survival (PFS) and overall survival for patients with confirmed GZL were 39% and 95%, respectively, vs 58% and 85%, respectively, for reclassified cases ( P = .19 and P = .15, respectively). Interestingly, NS grade 2 reclassified patients had similar PFS as GZL consensus-confirmed cases. For prognostication of GZL cases, hypoalbuminemia was a negative factor (3-year PFS, 12% vs 64%; P = .01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab (CHOP±R) was associated with improved 3-year PFS (70% vs 20%; P = .03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed.

Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL

PubMed Central

Pilichowska, Monika; Pittaluga, Stefania; Ferry, Judith A.; Hemminger, Jessica; Chang, Hong; Kanakry, Jennifer A.; Sehn, Laurie H.; Feldman, Tatyana; Abramson, Jeremy S.; Kritharis, Athena; Hernandez-Ilizaliturri, Francisco J.; Lossos, Izidore S.; Press, Oliver W.; Fenske, Timothy S.; Friedberg, Jonathan W.; Vose, Julie M.; Blum, Kristie A.; Jagadeesh, Deepa; Woda, Bruce; Gupta, Gaurav K.; Gascoyne, Randy D.; Jaffe, Elaine S.

2017-01-01

Gray zone lymphoma (GZL) is described as sharing features with classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 North American academic centers were evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universal B-cell derivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+, 83%; PAX5+, 100%; BCL6+, 20%; MUM1+, 100%; CD30+, 92%; EBV+, 4%). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n = 27 (including n = 10 NS grade 2); lymphocyte predominant HL, n = 4; DLBCL, n = 4; EBV+ DLBCL, n = 3; primary mediastinal large BCL n = 2; lymphocyte-rich cHL and BCL–not otherwise specified, n = 1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69% vs 41%; P = .038) and less likely more than 1 extranodal site (0% vs 25%; P = .019). With a 44-month median follow-up, 3-year progression-free survival (PFS) and overall survival for patients with confirmed GZL were 39% and 95%, respectively, vs 58% and 85%, respectively, for reclassified cases (P = .19 and P = .15, respectively). Interestingly, NS grade 2 reclassified patients had similar PFS as GZL consensus-confirmed cases. For prognostication of GZL cases, hypoalbuminemia was a negative factor (3-year PFS, 12% vs 64%; P = .01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab (CHOP±R) was associated with improved 3-year PFS (70% vs 20%; P = .03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed. PMID:29296913

Inward rectifier potassium channels in the HL-1 cardiomyocyte-derived cell line.

PubMed

Goldoni, Dana; Zhao, YouYou; Green, Brian D; McDermott, Barbara J; Collins, Anthony

2010-11-01

HL-1 is a line of immortalized cells of cardiomyocyte origin that are a useful complement to native cardiomyocytes in studies of cardiac gene regulation. Several types of ion channel have been identified in these cells, but not the physiologically important inward rectifier K(+) channels. Our aim was to identify and characterize inward rectifier K(+) channels in HL-1 cells. External Ba(2+) (100 µM) inhibited 44 ± 0.05% (mean ± s.e.m., n = 11) of inward current in whole-cell patch-clamp recordings. The reversal potential of the Ba(2+)-sensitive current shifted with external [K(+)] as expected for K(+)-selective channels. The slope conductance of the inward Ba(2+)-sensitive current increased with external [K(+)]. The apparent Kd for Ba(2+) was voltage dependent, ranging from 15 µM at -150  mV to 148 µM at -75  mV in 120  mM external K(+). This current was insensitive to 10 µM glybenclamide. A component of whole-cell current was sensitive to 150 µM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), although it did not correspond to the Ba(2+)-sensitive component. The effect of external 1 mM Cs(+) was similar to that of Ba(2+). Polymerase chain reaction using HL-1 cDNA as template and primers specific for the cardiac inward rectifier K(ir)2.1 produced a fragment of the expected size that was confirmed to be K(ir)2.1 by DNA sequencing. In conclusion, HL-1 cells express a current that is characteristic of cardiac inward rectifier K(+) channels, and express K(ir)2.1 mRNA. This cell line may have use as a system for studying inward rectifier gene regulation in a cardiomyocyte phenotype. © 2010 Wiley-Liss, Inc.

Effect of feeding long or short wheat hay v. wheat silage in the ration of lactating cows on intake, milk production and digestibility.

PubMed

Shaani, Y; Nikbachat, M; Yosef, E; Ben-Meir, Y; Mizrahi, I; Miron, J

2017-12-01

The objective of this study was to evaluate in lactating cows the effect of either chopping or ensiling of wheat roughage on: intake, digestibility, lactation performance and animal behavior. Three groups of 14 lactating cows each, were fed total mixed rations (TMRs) based on either long wheat hay (HL), short wheat hay (HS) or wheat silage (SI), as the sole roughage source (30% of TMR dry matter (DM)). Parameters examined: sorting behavior, DM intake, milk yield and composition, rumination, recumbence, average daily rumen pH, digesta passage rate, and in-vivo digestibility. Performance data was summarized by day and analyzed using a proc-mixed model. The content of physically effective neutral detergent fiber (peNDF) was similar in the HL and SI and lower in the HS, resulting in similar differences among the three corresponding TMRs. In vitro DM digestibility of wheat silage was higher than that of the two hays (65.6% v. 62.8%) resulting in higher in vitro DM digestibility of the SI-TMR compared with the hay-based TMRs (79.3 v. 77.0%). HS-TMR was better than HL- or SI-TMRs at preventing feed sorting by cows after 12 or 24 h eating of the diets. Cows fed HS-TMR consumed more DM and NDF but less peNDF than the other two groups. Average daily rumen pH was similar in the three groups, but daily rumination time was highest in the cows fed HS-TMR. Rumen retention time was longest in cows fed HL-TMR. DM digestibility in cows fed SI-TMR was higher than that of HS and HL groups (65.2%, 61.8% and 62.4%, respectively), but NDF digestibility was similar in the three treatments. The highest intake of digestible DM was observed in cows fed SI-TMR, HS cows were intermediate and HL cows were the lowest. Consequently, cows fed SI-TMR had higher yields of milk, 4% fat corrected milk and energy-corrected milk (47.1, 42.9 and 43.2 kg/day, respectively) than cows fed HS-TMR (45.7, 41.0 and 41.0 kg/day, respectively) or HL-TMR (44.1, 40.3 and 40.3 kg/day, respectively). Net energy production (NEL+M+gain) per kg DM intake was highest in the SI-TMR, lowest in the HS-TMR and intermediate in the HL-TMR (1.52, 1.40 and 1.45, respectively). Animal welfare, as expressed in daily recumbence time and BW gain was similar in the SI and HS groups and higher than the HL cows.

Relationship between mosquito (Diptera: Culicidae) landing rates on a human subject and numbers captured using CO2-baited light traps.

PubMed

Barnard, D R; Knue, G J; Dickerson, C Z; Bernier, U R; Kline, D L

2011-06-01

Capture rates of insectary-reared female Aedes albopictus (Skuse), Anopheles quadrimaculatus Say, Culex nigripalpus Theobald, Culex quinquefasciatus Say and Aedes triseriatus (Say) in CDC-type light traps (LT) supplemented with CO2 and using the human landing (HL) collection method were observed in matched-pair experiments in outdoor screened enclosures. Mosquito responses were compared on a catch-per-unit-effort basis using regression analysis with LT and HL as the dependent and independent variables, respectively. The average number of mosquitoes captured in 1 min by LT over a 24-h period was significantly related to the average number captured in 1 min by HL only for Cx. nigripalpus and Cx. quinquefasciatus. Patterns of diel activity indicated by a comparison of the mean response to LT and HL at eight different times in a 24-h period were not superposable for any species. The capture rate efficiency of LT when compared with HL was ≤15% for all mosquitoes except Cx. quinquefasciatus (43%). Statistical models of the relationship between mosquito responses to each collection method indicate that, except for Ae. albopictus, LT and HL capture rates are significantly related only during certain times of the diel period. Estimates of mosquito activity based on observations made between sunset and sunrise were most precise in this regard for An. quadrimaculatus and Cx. nigripalpus, as were those between sunrise and sunset for Cx. quinquefasciatus and Ae. triseriatus.

The Hispanic and Latino dentist workforce in the United States.

PubMed

Mertz, Elizabeth; Wides, Cynthia; Calvo, Jean; Gates, Paul

2017-03-01

The purpose of this paper is to describe the Hispanic/Latino (H/L) dentist workforce, their general practice patterns, and their contributions to oral health care for H/L and underserved patients. A national sample survey of underrepresented minority dentists was conducted in 2012 and received a 35.4 percent response rate for self-reported H/L dentists. Data were weighted for selection and response bias to be nationally representative. A workforce profile of H/L dentists was created using descriptive and multivariable statistics and published data. Among all H/L dentists (weighted n = 5,748), 31.9 percent self-identify their origin as Mexican, 13.4 percent as Puerto Rican, 13.0 percent as Cuban, and 41.7 percent as another H/L group. The largest share of H/L dentists are male, married, and have children under age 18. Fifty percent of H/L dentists are foreign-born and 25 percent are foreign-trained. H/L dentists report higher than average educational debt, with those completing International Dentist Programs reporting the highest debt load. Sixty-nine percent of clinically active H/L dentists own their own practices, and 85 percent speak Spanish in their practice. Among clinical H/L dentists, 7 percent work in safety-net settings, 40 percent primarily treat underserved populations, and, on average, 42 percent of their patient population is H/L. H/L dental providers are underrepresented in the dentist population, and those that are in practice shoulder a disproportionate share of dental care for minority and underserved communities. Improving the workforce diversity of dental providers is a critical part of strategy to address the high burden of dental disease in the H/L population. © 2016 American Association of Public Health Dentistry.

The Hispanic and Latino Dentist Workforce in the United State

PubMed Central

Mertz, Elizabeth; Wides, Cynthia; Calvo, Jean; Gates, Paul

2017-01-01

Objectives The purpose of this paper is to describe the Hispanic/Latino (H/L) dentist workforce, their general practice patterns, and their contributions to oral health care for H/L and underserved patients. Methods A national sample survey of underrepresented minority dentists was conducted in 2012 and received a 35.4% response rate for self-reported H/L dentists. Data were weighted for selection and response bias to be nationally representative. A workforce profile of H/L dentists was created using descriptive and multivariable statistics and published data. Results Among all H/L dentists (weighted n=5,748), 31.9% self-identify their origin as Mexican, 13.4% as Puerto Rican, 13.0% as Cuban, and 41.7% as another H/L group. The largest share of H/L dentists are male, married, and have children under age 18. Fifty percent of H/L dentists are foreign-born and 25% are foreign-trained. H/L dentists report higher than average educational debt, with those completing International Dentist Programs reporting the highest debt load. Sixty-nine percent of clinically active H/L dentists own their own practices, and 85% speak Spanish in their practice. Among clinical H/L dentists, 7% work in safety-net settings, 40% primarily treat underserved populations, and, on average, 42% of their patient population is H/L. Conclusions H/L dental providers are drastically underrepresented in the dentist population, and those that are in practice shoulder a disproportionate share of dental care for minority and underserved communities. Improving the workforce diversity of dental providers is a critical part of strategy to address the unacceptably high burden of dental disease in the H/L population. PMID:28025830

Description and status update on GELLO: a proposed standardized object-oriented expression language for clinical decision support.

PubMed

Sordo, Margarita; Boxwala, Aziz A; Ogunyemi, Omolola; Greenes, Robert A

2004-01-01

A major obstacle to sharing computable clinical knowledge is the lack of a common language for specifying expressions and criteria. Such a language could be used to specify decision criteria, formulae, and constraints on data and action. Al-though the Arden Syntax addresses this problem for clinical rules, its generalization to HL7's object-oriented data model is limited. The GELLO Expression language is an object-oriented language used for expressing logical conditions and computations in the GLIF3 (GuideLine Interchange Format, v. 3) guideline modeling language. It has been further developed under the auspices of the HL7 Clinical Decision Support Technical Committee, as a proposed HL7 standard., GELLO is based on the Object Constraint Language (OCL), because it is vendor-independent, object-oriented, and side-effect-free. GELLO expects an object-oriented data model. Although choice of model is arbitrary, standardization is facilitated by ensuring that the data model is compatible with the HL7 Reference Information Model (RIM).

Power measurement system of ECRH on HL-2A

NASA Astrophysics Data System (ADS)

Wang, He; Lu, Zhihong; Kubo, Shin; Chen, Gangyu; Wang, Chao; Zhou, Jun; Huang, Mei; Rao, Jun

2015-03-01

Electron Cyclotron Resonance Heating (ECRH) is one of the main auxiliary heating systems for HL-2A tokamak. The ECRH system with total output power 5MW has been equipped on HL-2A which include 6 sets of 0.5MW/1.0s at a frequency of 68GHz and 2 sets of 1MW/3s at a frequency of 140GHz. The power is one of important parameters in ECRH system. In this paper, the method for measuring the power of ECRH system on HL-2A is introduced which include calorimetric techniques and directional coupler. Calorimetric techniques is an existing method, which is used successfully in ECRH commissioning and experiment, and the transmission efficiency of ECRH system is achieved by measuring the absorbed microwave power in the Match Optical Unit (MOU), gyrotron output window and tours window of the EC system use this method. Now base on the theory of electromagnetic coupling through apertures, directional couplers are being designed, which is a new way for us.

Prevalence and management of helminthiasis among underfives living with HIV/AIDS at Amana Hospital, Tanzania.

PubMed

Mwambete, Kennedy D; Tunzo, Jones; Justin-Temu, Mary

2013-01-01

This was a cross-sectional study intended to assess the prevalence and management of helminthiasis (HL) among underfives living with HIV/AIDS (ULHA). Clinical histories of ULHA were scrutinized for HIV/AIDS status, antiretroviral therapy (ART), HL prevalence, and their management. About 364 ULHA were studied, 213 (58.5%) were girls and 151 (41.5%) were boys. Of the 364 ULHA, 171 (47.5%) had HL and 64.3% were treated with albendazole (ABZ). Trichuriasis was ascribed to 23.6% of HL. Majority (72.5%) of ULHA had a CD4 count below 200 cells/mm³. Direct association was observed between CD4 counts and HL. About 55% ULHA were on lamivudine (3TC)-stavudine (d4T)-nevirapine (NVP; LSN) combination therapy. The ABZ-LSN combination was frequently used for HIV/AIDS and HL management. High prevalence of HL and vivid correlation between HIV status and HL were observed. The LSN-ABZ combination was frequently employed for management of HIV/AIDS and HL. We recommended prompt diagnosis of HL to avoid acceleration of HIV infection to AIDS.

Adaptation to acidic soil is achieved by increased numbers of cis-acting elements regulating ALMT1 expression in Holcus lanatus.

PubMed

Chen, Zhi Chang; Yokosho, Kengo; Kashino, Miho; Zhao, Fang-Jie; Yamaji, Naoki; Ma, Jian Feng

2013-10-01

Yorkshire fog (Holcus lanatus), which belongs to the Poaceae family and is a close relative of the agronomic crop oat (Avena sativa), is a widely adaptable grass species that is able to grow on highly acidic soils with high levels of Al, but the mechanism underlying the high Al tolerance is unknown. Here, we characterized two accessions of H. lanatus collected from an acid plot (soil pH 3.6, HL-A) and a neutral plot (pH 7.1, HL-N) in terms of Al tolerance, organic acid anion secretion and related gene expression. In response to Al (pH 4.5), the HL-A roots secreted approximately twice as much malate as the HL-N roots, but there was no difference in citrate secretion. Cloning of the gene HlALMT1 responsible for malate secretion showed that the encoded amino acid sequence did not differ between two accessions, but the expression level in the outer cell layers of the HL-A roots was twice as high as in the HL-N roots. This difference was not due to the genomic copy number, but was due to the number of cis-acting elements for an Al-responsive transcription factor (HlART1) in the promoter region of HlALMT1, as demonstrated by both a yeast one-hybrid assay and a transient assay in tobacco protoplasts. Furthermore, introduction of HlALMT1 driven by the HL-A promoter into rice resulted in significantly more Al-induced malate secretion than introduction of HlALMT1 driven by the HL-N promoter. These findings indicate that the adaptation of H. lanatus to acidic soils may be achieved by increasing number of cis-acting elements for ART1 in the promoter region of the HlALMT1 gene, enhancing the expression of HlALMT1 and the secretion of malate. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Birth weight and risk of paediatric Hodgkin lymphoma: Findings from a population-based record linkage study in California.

PubMed

Triebwasser, Corey; Wang, Rong; DeWan, Andrew T; Metayer, Catherine; Morimoto, Libby; Wiemels, Joseph L; Kadan-Lottick, Nina; Ma, Xiaomei

2016-12-01

To evaluate the relationship between birth weight (along with a variety of pre and perinatal characteristics) and the risk of paediatric Hodgkin lymphoma (HL) diagnosed at age <20 years. We linked California statewide birth records from 1978-2009 and cancer diagnosis data from 1988-2011 to conduct a population-based case-control study with 1216 cases and 4485 controls (matched on birth month and year, sex, and race/ethnicity). Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) of paediatric HL overall and by age of diagnosis, controlling for other perinatal factors. Compared to children with a normal birth weight (2500-3999 g), those who had a high birth weight (≥4000 g) had an increased risk of paediatric HL overall (OR = 1.23, 95% CI: 1.02-1.48) after adjusting for birth order, maternal age at the time of delivery, and paternal age at the time of delivery. The magnitude of association appeared larger for subgroups of children whose age of diagnosis was 0-10 years (OR = 1.56, 95% CI: 1.04-2.24) or 15-19 years (OR = 1.43, 95% CI: 1.11-1.83), while no association was observed in 11-14 year olds. Compared with firstborn children, those who were third or higher in birth order had a reduced risk of paediatric HL overall (OR = 0.80, 95% CI: 0.67-0.95), and this association also varied by age of diagnosis. In this study with the largest number of paediatric HL cases, high birth weight was associated with an increased disease risk for most but not all ages of diagnosis. The different findings by age of diagnosis regarding both birth weight and birth order underscore the importance to stratify paediatric HL by age at diagnosis in future etiological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protodioscin, Isolated from the Rhizome of Dioscorea tokoro Collected in Northern Japan is the Major Antiproliferative Compound to HL-60 
Leukemic Cells

PubMed Central

Oyama, Manami; Tokiwano, Tetsuo; Kawaii, Satoru; Yoshida, Yasunori; Mizuno, Kouichi; Oh, Keimei; Yoshizawa, Yuko

2017-01-01

Abstract: Background: The rhizome of Oni-dokoro (a wild yam, Dioscorea tokoro) has extremely bitter taste and is not generally regarded edible;, however, in northern part of Japan, such as Iwate and a part of Aomori, it is used as health promoting food. To clarify the reason, we examined the biologically active compounds in the rhizome collected at Iwate and compared them from the other area in literature. Methods: The acetonitrile extract from northern part of Japan was purified by bioassay-guided separation using antiproliferative activity to human leukemia HL-60 cell, and protodioscin (PD) was isolated and identified by instrumental analyses as the major active compound. Results: PD known as a saponin with four sugar moieties, an inhibitor for platelet aggregation, and a low density lipoprotein (LPL) lowering agent, displayed strong growth inhibitory effect to HL-60. The literature search suggested that the rhizome from other area contained dioscin and other saponins with three sugar moieties as their major component. We assume that the edible and health promoting effect of the rhizome in the particular area is partially derived from these different components. Conclusion: We were interested in the differences of utilization in the rhizome of wild yam Dioscorea tokoro, and examined the chemical composition in the rhizome to find protodioscin as antiproliferative compound to HL-60. In the report from other area, the rhizome exhibited dioscin as the major compound. Our study indicated that the protodioscin/dioscin composition varied regionally, although the reason is still needs to be investigated. PMID:28579930

Protodioscin, Isolated from the Rhizome of Dioscorea tokoro Collected in Northern Japan is the Major Antiproliferative Compound to HL-60 
Leukemic Cells.

PubMed

Oyama, Manami; Tokiwano, Tetsuo; Kawaii, Satoru; Yoshida, Yasunori; Mizuno, Kouichi; Oh, Keimei; Yoshizawa, Yuko

2017-06-01

The rhizome of Oni-dokoro (a wild yam, Dioscorea tokoro) has extremely bitter taste and is not generally regarded edible;, however, in northern part of Japan, such as Iwate and a part of Aomori, it is used as health promoting food. To clarify the reason, we examined the biologically active compounds in the rhizome collected at Iwate and compared them from the other area in literature. The acetonitrile extract from northern part of Japan was purified by bioassay-guided separation using antiproliferative activity to human leukemia HL-60 cell, and protodioscin (PD) was isolated and identified by instrumental analyses as the major active compound. PD known as a saponin with four sugar moieties, an inhibitor for platelet aggregation, and a low density lipoprotein (LPL) lowering agent, displayed strong growth inhibitory effect to HL-60. The literature search suggested that the rhizome from other area contained dioscin and other saponins with three sugar moieties as their major component. We assume that the edible and health promoting effect of the rhizome in the particular area is partially derived from these different components. We were interested in the differences of utilization in the rhizome of wild yam Dioscorea tokoro, and examined the chemical composition in the rhizome to find protodioscin as antiproliferative compound to HL-60. In the report from other area, the rhizome exhibited dioscin as the major compound. Our study indicated that the protodioscin/dioscin composition varied regionally, although the reason is still needs to be investigated.

Characterisation of re-entrant circuit (or rotational activity) in vitro using the HL1-6 myocyte cell line.

PubMed

Houston, Charles; Tzortzis, Konstantinos N; Roney, Caroline; Saglietto, Andrea; Pitcher, David S; Cantwell, Chris D; Chowdhury, Rasheda A; Ng, Fu Siong; Peters, Nicholas S; Dupont, Emmanuel

2018-06-01

Fibrillation is the most common arrhythmia observed in clinical practice. Understanding of the mechanisms underlying its initiation and maintenance remains incomplete. Functional re-entries are potential drivers of the arrhythmia. Two main concepts are still debated, the "leading circle" and the "spiral wave or rotor" theories. The homogeneous subclone of the HL1 atrial-derived cardiomyocyte cell line, HL1-6, spontaneously exhibits re-entry on a microscopic scale due to its slow conduction velocity and the presence of triggers, making it possible to examine re-entry at the cellular level. We therefore investigated the re-entry cores in cell monolayers through the use of fluorescence optical mapping at high spatiotemporal resolution in order to obtain insights into the mechanisms of re-entry. Re-entries in HL1-6 myocytes required at least two triggers and a minimum colony area to initiate (3.5 to 6.4 mm 2 ). After electrical activity was completely stopped and re-started by varying the extracellular K + concentration, re-entries never returned to the same location while 35% of triggers re-appeared at the same position. A conduction delay algorithm also allows visualisation of the core of the re-entries. This work has revealed that the core of re-entries is conduction blocks constituted by lines and/or groups of cells rather than the round area assumed by the other concepts of functional re-entry. This highlights the importance of experimentation at the microscopic level in the study of re-entry mechanisms. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Health Literacy of Living Kidney Donors and Kidney Transplant Recipients

PubMed Central

Dageforde, Leigh Anne; Petersen, Alec W.; Feurer, Irene D.; Cavanaugh, Kerri L.; Harms, Kelly A.; Ehrenfeld, Jesse M.; Moore, Derek E.

2015-01-01

Background Health literacy (HL) may be a mediator for known socioeconomic and racial disparities in living kidney donation. Methods We evaluated the associations of patient and demographic characteristics with HL in living kidney donors (LD), living donor kidney transplant recipients (LDR), and deceased donor recipients (DDR) in a single center retrospective review of patients undergoing kidney donation or transplantation from September 2010 to July 2012. HL and demographic data were collected. HL was assessed via the Short Literacy Survey (SLS) comprising three self-reported screening questions scored using the 5-point Likert scale [low (3-8), moderate (9-14), high (15)]. Chi-square and logistic regression were used to test factors associated with lower HL. Results The sample included 360 adults (105 LD, 103 LDR, 152 DDR; 46±14 years; 70% white; 56% male; 14±3 years of education). HL scores were skewed (49% high, 41% moderate, 10% low). The distribution of HL categories differed significantly among groups (p=0.019). After controlling for age, race, gender, education and a race-education interaction term, DDR were more likely to have moderate or low HL than LDR (OR 1.911; 95%CI 1.096, 3.332; p=0.022) Conclusions Overall, living donors had high HL. The distribution of low, moderate and high HL differed significantly between LD, DDR and LDR. DDR had a higher likelihood of having low HL than LDR. Screening kidney transplant candidates and donors for lower HL may identify barriers to living donation. Future interventions addressing HL may be important to increase living donation and reduce disparities. PMID:24573114

Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph)

PubMed Central

Kamper-Jørgensen, M.; Rostgaard, K.; Glaser, S. L.; Zahm, S. H.; Cozen, W.; Smedby, K. E.; Sanjosé, S.; Chang, E. T.; Zheng, T.; La Vecchia, C.; Serraino, D.; Monnereau, A.; Kane, E. V.; Miligi, L.; Vineis, P.; Spinelli, J. J.; McLaughlin, J. R.; Pahwa, P.; Dosman, J. A.; Vornanen, M.; Foretova, L.; Maynadie, M.; Staines, A.; Becker, N.; Nieters, A.; Brennan, P.; Boffetta, P.; Cocco, P.; Hjalgrim, H.

2013-01-01

Summary Background The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes. Patients and methods Through the InterLymph Consortium, 12 case–control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein–Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls. Results Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01–1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29–1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27–2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90–1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72–1.44) was not increased. Conclusion These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified. PMID:23788758

Lethality to leukemia cell lines of DNA interstrand cross-links generated by Cloretazine derived alkylating species

PubMed Central

Penketh, Philip G.; Baumann, Raymond P.; Ishiguro, Kimiko; Shyam, Krishnamurthy; Seow, Helen A.; Sartorelli, Alan C.

2010-01-01

Cloretazine [1, 2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]-hydrazine; VNP40101M; 101M] is a relatively new prodrug with activity in elderly acute myelogenous leukemia patients. Its therapeutic action is due largely to the production of 1-(3-cytosinyl),2-(1-guanyl)ethane cross-links (G-C ethane cross-links) in DNA. The number of cross-links produced in three experimental leukemia lines (L1210, U937 and HL-60) were fewer than 10 per genome at their respective LC50 concentrations. Only 1 in approximately 20,000 90CE molecules produce a cross-link in the AGT (O6-alkylguanine-DNA alkyltransferase) negative L1210 and U937 cell lines and 1 in 400,000 in the AGT positive HL-60 cell line. PMID:18479747

Predictors of health literacy and numeracy concordance among adolescent with special health care needs and their parents

PubMed Central

Chisolm, Deena J; Sarkar, Madhurima; Kelleher, Kelly J.; Sanders, Lee M.

2015-01-01

Background Parent and teen health literacies (HL) are employed as teens with chronic illnesses transition to health self-management and the adult health system. This study explores the relationships between parent and teen HL. Methods Teens ages 12-18 with chronic conditions and their parents, sampled from a pediatric Medicaid ACO, completed an interview assessing HL and self-reported competence with written and numeric health information. Rates of teen and parent HL, degree of concordance, and relationship between concordance and teen-reported competence with health materials were measured. Results Half (52%) of teens had adequate HL. 62% of teens reported competence with written health materials and 69% with numeric information. Correlation between parent and teen HL was modest but significant (phi=0.13; p=0.03). 47% of parent-teen dyads were concordant for adequate HL while 10% were concordant inadequate. Adequate teen HL was associated with parental adequate HL and parental education. Discordance was associated with self-reported competence with written material and numeric material. Conclusion Over half of parent-teen dyads had at least one member with less than adequate health literacy and parent-teen HL concordance were associated with teen perception of health literacy. These findings support the consideration of both independent and dyad HL levels in adolescent care. PMID:26513030

[Drug resistance reversal of HL-60/ADR cells by simultaneous suppression of XIAP and MRP].

PubMed

Wang, Xiao-Fang; Wang, Chun; Qin, You-Wen; Yan, Shi-Ke; Gao, Yan-Rong

2006-12-01

This study was purposed to explore the mechanisms of drug resistance of HL-60/ADR cells and to compare the reversal drug-resistance effects of antisense oligonucleotides (AS ODN) of XIAP (X-linked inhibitor of apoptosis protein) and AS ODNs of MRP (multidrug resistance-associated protein) by use alone or in combination. Reverse transcription-PCR and Western blot were applied to detect the expression of XIAP, BCL-2, MRP and MDR1 in mRNA and protein levels of HL-60 cells and HL-60/ADR cells, respectively. Fully phosphorothioated AS ODN of XIAP and MRP was delivered into HL-60/ADR cells with Lipofectamine 2000 in the form of liposome-ODN complexes alone or in combination. CCK-8 cell viability assay was used to determine the effect of AS ODN of XIAP and MRP used alone or in combination on the chemotherapy sensitivity of HL-60/ADR cells to daunorubicin (DNR). Reverse transcription-PCR and Western blot were applied to examine the changes of XIAP, MRP in mRNA and protein levels respectively. The results showed that MRP and XIAP were both significantly higher in HL-60/ADR cells than those in HL-60 cells. AS ODN of XIAP and MRP down-regulated the expression of XIAP and MRP in HL-60/ADR cells and increased the sensitivity of HL-60/ADR cells to DNR, respectively. AS ODN of XIAP + MRP did not enhance the inhibition expression of XIAP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR significantly as compared with AS ODN of XIAP (P < 0.05). AS ODN of XIAP + MRP did not increase the concentration of DNR nor enhanced the inhibition expression of MRP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR significantly (P < 0.05), as compared with AS ODN of MRP. It is concluded that both XIAP and MRP may be involved in the drug resistance mechanisms of HL-60/ADR cells. Drug-resistance of HL-60/ADR cells can be reversed significantly when antisense oligonucleotides of XIAP and MRP were used in combination.

Elastase inhibitors as potential therapies for ELANE-associated neutropenia.

PubMed

Makaryan, Vahagn; Kelley, Merideth L; Fletcher, Breanna; Bolyard, Audrey Anna; Aprikyan, A Andrew; Dale, David C

2017-10-01

Mutations in ELANE , the gene for neutrophil elastase (NE), a protease expressed early in neutrophil development, are the most frequent cause of cyclic (CyN) and severe congenital neutropenia (SCN). We hypothesized that inhibitors of NE, acting either by directly inhibiting enzymatic activity or as chaperones for the mutant protein, might be effective as therapy for CyN and SCN. We investigated β-lactam-based inhibitors of human NE (Merck Research Laboratories, Kenilworth, NJ, USA), focusing on 1 inhibitor called MK0339, a potent, orally absorbed agent that had been tested in clinical trials and shown to have a favorable safety profile. Because fresh, primary bone marrow cells are rarely available in sufficient quantities for research studies, we used 3 cellular models: patient-derived, induced pluripotent stem cells (iPSCs); HL60 cells transiently expressing mutant NE; and HL60 cells with regulated expression of the mutant enzyme. In all 3 models, the cells expressing the mutant enzyme had reduced survival as measured with annexin V and FACS. Coincubation with the inhibitors, particularly MK0339, promoted cell survival and increased formation of mature neutrophils. These studies suggest that cell-permeable inhibitors of neutrophil elastase show promise as novel therapies for ELANE -associated neutropenia. © Society for Leukocyte Biology.

Evidence-based guidelines for recommending cochlear implantation for young children: Audiological criteria and optimizing age at implantation.

PubMed

Leigh, Jaime R; Dettman, Shani J; Dowell, Richard C

2016-01-01

Establish up-to-date evidence-based guidelines for recommending cochlear implantation for young children. Speech perception results for early-implanted children were compared to children using traditional amplification. Equivalent pure-tone average (PTA) hearing loss for cochlear implant (CI) users was established. Language of early-implanted children was assessed over six years and compared to hearing peers. Seventy-eight children using CIs and 62 children using traditional amplification with hearing losses ranging 25-120 dB HL PTA (speech perception study). Thirty-two children who received a CI before 2.5 years of age (language study). Speech perception outcomes suggested that children with a PTA greater than 60 dB HL have a 75% chance of benefit over traditional amplification. More conservative criteria applied to the data suggested that children with PTA greater than 82 dB HL have a 95% chance of benefit. Children implanted under 2.5 years with no significant cognitive deficits made normal language progress but retained a delay approximately equal to their age at implantation. Hearing-impaired children under three years of age may benefit from cochlear implantation if their PTA exceeds 60 dB HL bilaterally. Implantation as young as possible should minimize any language delay resulting from an initial period of auditory deprivation.

Watermelon (Citrullus lanatus) hydroperoxide lyase greatly increases C6 aldehyde formation in transgenic leaves.

PubMed

Fukushige, Hirotada; Hildebrand, David F

2005-03-23

Fatty acid hydroperoxide lyase (HL) is the key enzyme for the production of the "green note"compounds, leaf aldehyde [(2E)-hexenal] and leaf alcohol [(3Z)-hexenol], in plant tissues. A cDNA encoding HL was cloned from leaves of watermelon (Citrullus lanatus) and expressed in Nicotiana tabacum. The enzyme is 3 times more active with 13-hydroperoxylinolenic acid than with 13-hydroperoxylinoleic acid. The activity against 9-hydroperoxides of polyunsaturated fatty acids is minimal. Enzyme activity of the watermelon HL in the transgenic leaves was approximately 50 times higher than endogenous HL activity in the wild-type N. tabacum plants. When compared with Arabidopsis HL also expressed in N. tabacum, the highest HL activity is 10 times higher in watermelon HL overexpressing leaves than in Arabidopsis HL overexpressers.

What is Health Level 7?

PubMed

Kabachinski, Jeff

2006-01-01

HL7 is a huge undertaking and continues to grow. We talked about certain main themes of the spec that I've found interesting and thought you might too. You can always find additional information-especially from the HL7 website itself at www.hl7.org or www.altisinc.com/ IE/hl7.html. The main thing to remember is that HL7 is a specification for describing, formatting, encoding, and sharing of clinical and administrative data in healthcare. An easy way to remember that is that the 7 in HL7 refers to the Application layer in the OSI model. The next time someone talks about their HL7 software or application, you'll know that they really mean their HL7 compliant software or application. Then be sure to ask them how many composites are in their OBX segments!

Age- and sex-dependent regression models for predicting the live weight of West African Dwarf goat from body measurements.

PubMed

Sowande, O S; Oyewale, B F; Iyasere, O S

2010-06-01

The relationships between live weight and eight body measurements of West African Dwarf (WAD) goats were studied using 211 animals under farm condition. The animals were categorized based on age and sex. Data obtained on height at withers (HW), heart girth (HG), body length (BL), head length (HL), and length of hindquarter (LHQ) were fitted into simple linear, allometric, and multiple-regression models to predict live weight from the body measurements according to age group and sex. Results showed that live weight, HG, BL, LHQ, HL, and HW increased with the age of the animals. In multiple-regression model, HG and HL best fit the model for goat kids; HG, HW, and HL for goat aged 13-24 months; while HG, LHQ, HW, and HL best fit the model for goats aged 25-36 months. Coefficients of determination (R(2)) values for linear and allometric models for predicting the live weight of WAD goat increased with age in all the body measurements, with HG being the most satisfactory single measurement in predicting the live weight of WAD goat. Sex had significant influence on the model with R(2) values consistently higher in females except the models for LHQ and HW.

Obesity Increases Prevalence of Colonic Adenomas at Screening Colonoscopy: A Canadian Community-Based Study

PubMed Central

Chen, Grant I.; Devlin, Tim; Gibbs, Alison; Murray, Iain C.; Tran, Stanley; Weigensberg, Corey

2017-01-01

Background and Aims Obesity is a risk factor for colorectal neoplasia. We examined the influence of obesity and metabolic syndrome (MetS) on prevalence of neoplasia at screening colonoscopy. Methods We evaluated 2020 subjects undergoing first screening colonoscopy. Body mass index (BMI) was calculated at enrolment. Hyperlipidemia (HL), hypertension (HT), and diabetes mellitus (DM) were identified. Details of colonoscopy, polypectomy, and histology were recorded. Odds for adenomas (A) and advanced adenomas (ADV) in overweight (BMI 25.1–30) and obese (BMI > 30) subjects were assessed by multinomial regression, adjusted for covariates. Analyses included relationships between HL, HT, DM, age, tobacco usage, and neoplasia. Discriminatory power of HT, HL, DM, and BMI for neoplasia was assessed by binary logistic regression. Odds were calculated for neoplasia in each colonic segment related to BMI. Results A and ADV were commoner in overweight and obese males, obese females, older subjects, and smokers. HL, HT, and DM were associated with increased odds for neoplasia, significantly for A with hypertension. BMI alone predicted neoplasia as well as HT, HL, DM, or combinations thereof. All segments of the colon were affected. Multiple polyps were particularly prevalent in the obese. Conclusions Obesity and MetS are risk factors for colonic neoplasia in a Canadian population. PMID:28781966

Hearing loss in Waardenburg syndrome: a systematic review.

PubMed

Song, J; Feng, Y; Acke, F R; Coucke, P; Vleminckx, K; Dhooge, I J

2015-06-22

Waardenburg syndrome (WS) is a rare genetic disorder characterized by hearing loss (HL) and pigment disturbances of hair, skin and iris. Classifications exist based on phenotype and genotype. The auditory phenotype is inconsistently reported among the different Waardenburg types and causal genes, urging the need for an up-to-date literature overview on this particular topic. We performed a systematic review in search for articles describing auditory features in WS patients along with the associated genotype. Prevalences of HL were calculated and correlated with the different types and genes of WS. Seventy-three articles were included, describing 417 individual patients. HL was found in 71.0% and was predominantly bilateral and sensorineural. Prevalence of HL among the different clinical types significantly differed (WS1: 52.3%, WS2: 91.6%, WS3: 57.1%, WS4: 83.5%). Mutations in SOX10 (96.5%), MITF (89.6%) and SNAI2 (100%) are more frequently associated with hearing impairment than other mutations. Of interest, the distinct disease-causing genes are able to better predict the auditory phenotype compared with different clinical types of WS. Consequently, it is important to confirm the clinical diagnosis of WS with molecular analysis in order to optimally inform patients about the risk of HL. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Precision searches in dijets at the HL-LHC and HE-LHC

NASA Astrophysics Data System (ADS)

Chekanov, S. V.; Childers, J. T.; Proudfoot, J.; Wang, R.; Frizzell, D.

2018-05-01

This paper explores the physics reach of the High-Luminosity Large Hadron Collider (HL-LHC) for searches of new particles decaying to two jets. We discuss inclusive searches in dijets and b-jets, as well as searches in semi-inclusive events by requiring an additional lepton that increases sensitivity to different aspects of the underlying processes. We discuss the expected exclusion limits for generic models predicting new massive particles that result in resonant structures in the dijet mass. Prospects of the Higher-Energy LHC (HE-LHC) collider are also discussed. The study is based on the Pythia8 Monte Carlo generator using representative event statistics for the HL-LHC and HE-LHC running conditions. The event samples were created using supercomputers at NERSC.

Health literacy and health communication

PubMed Central

2010-01-01

Health communication consists of interpersonal or mass communication activities focused on improving the health of individuals and populations. Skills in understanding and applying information about health issues are critical to this process and may have a substantial impact on health behaviors and health outcomes. These skills have recently been conceptualized in terms of health literacy (HL). This article introduces current concepts and measurements of HL, and discusses the role of HL in health communication, as well as future research directions in this domain. Studies of HL have increased dramatically during the past few years, but a gap between the conceptual definition of HL and its application remains. None of the existing instruments appears to completely measure the concept of HL. In particular, studies on communication/interaction and HL remain limited. Furthermore, HL should be considered not only in terms of the characteristics of individuals, but also in terms of the interactional processes between individuals and their health and social environments. Improved HL may enhance the ability and motivation of individuals to find solutions to both personal and public health problems, and these skills could be used to address various health problems throughout life. The process underpinning HL involves empowerment, one of the major goals of health communication. PMID:21054840

Early investigational drugs for hearing loss

PubMed Central

Mukherjea, Debashree; Ghosh, Sumana; Bhatta, Puspanjali; Sheth, Sandeep; Tupal, Srinivasan; Borse, Vikrant; Brozoski, Thomas; Sheehan, Kelly E; Rybak, Leonard P; Ramkumar, Vickram

2017-01-01

Introduction Sensorineural hearing loss (HL) is becoming a global phenomenon at an alarming rate. Nearly 600 million people have been estimated to have significant HL in at least one ear. There are several different causes of sensorineural HL included in this review of new investigational drugs for HL. They are noise-induced, drug-induced, sudden sensorineural HL, presbycusis and HL due to cytomegalovirus infections. Areas covered This review presents trends in research for new investigational drugs encompassing a variety of causes of HL. The studies presented here are the latest developments either in the research laboratories or in preclinical, Phase 0, Phase I or Phase II clinical trials for drugs targeting HL. Expert opinion While it is important that prophylactic measures are developed, it is extremely crucial that rescue strategies for unexpected or unavoidable cochlear insult be established. To achieve this goal for the development of drugs for HL, innovative strategies and extensive testing are required for progress from the bench to bedside. However, although a great deal of research needs to be done to achieve the ultimate goal of protecting the ear against acquired sensorineural HL, we are likely to see exciting breakthroughs in the near future. PMID:25243609

Four New Chloro-Eremophilane Sesquiterpenes from an Antarctic Deep-Sea Derived Fungus, Penicillium sp. PR19N-1

PubMed Central

Wu, Guangwei; Lin, Aiqun; Gu, Qianqun; Zhu, Tianjiao; Li, Dehai

2013-01-01

A new chloro-trinoreremophilane sesquiterpene 1, three new chlorinated eremophilane sesquiterpenes 2–4, together with a known compound, eremofortine C (5), were isolated from an Antarctic deep-sea derived fungus, Penicillium sp. PR19N-1. Structures were established using IR, HRMS, 1D and 2D NMR techniques. In addition, the plausible metabolic network of these isolated products is proposed. Compound 1 showed moderate cytotoxic activity against HL-60 and A549 cancer cell lines. PMID:23612371

Clinical data integration of distributed data sources using Health Level Seven (HL7) v3-RIM mapping

PubMed Central

2011-01-01

Background Health information exchange and health information integration has become one of the top priorities for healthcare systems across institutions and hospitals. Most organizations and establishments implement health information exchange and integration in order to support meaningful information retrieval among their disparate healthcare systems. The challenges that prevent efficient health information integration for heterogeneous data sources are the lack of a common standard to support mapping across distributed data sources and the numerous and diverse healthcare domains. Health Level Seven (HL7) is a standards development organization which creates standards, but is itself not the standard. They create the Reference Information Model. RIM is developed by HL7's technical committees. It is a standardized abstract representation of HL7 data across all the domains of health care. In this article, we aim to present a design and a prototype implementation of HL7 v3-RIM mapping for information integration of distributed clinical data sources. The implementation enables the user to retrieve and search information that has been integrated using HL7 v3-RIM technology from disparate health care systems. Method and results We designed and developed a prototype implementation of HL7 v3-RIM mapping function to integrate distributed clinical data sources using R-MIM classes from HL7 v3-RIM as a global view along with a collaborative centralized web-based mapping tool to tackle the evolution of both global and local schemas. Our prototype was implemented and integrated with a Clinical Database management Systems CDMS as a plug-in module. We tested the prototype system with some use case scenarios for distributed clinical data sources across several legacy CDMS. The results have been effective in improving information delivery, completing tasks that would have been otherwise difficult to accomplish, and reducing the time required to finish tasks which are used in collaborative information retrieval and sharing with other systems. Conclusions We created a prototype implementation of HL7 v3-RIM mapping for information integration between distributed clinical data sources to promote collaborative healthcare and translational research. The prototype has effectively and efficiently ensured the accuracy of the information and knowledge extractions for systems that have been integrated PMID:22104558

Evidence for Transfer of Membranes from Mesenchymal Stem Cells to HL-1 Cardiac Cells.

PubMed

Boomsma, Robert A; Geenen, David L

2014-01-01

This study examined the interaction of mouse bone marrow mesenchymal stem cells (MSC) with cardiac HL-1 cells during coculture by fluorescent dye labeling and then flow cytometry. MSC were layered onto confluent HL-1 cell cultures in a 1 : 4 ratio. MSC gained gap junction permeant calcein from HL-1 cells after 4 hours which was partially reduced by oleamide. After 20 hours, 99% MSC gained calcein, unaffected by oleamide. Double-labeling HL-1 cells with calcein and the membrane dye DiO resulted in transfer of both calcein and DiO to MSC. When HL-1 cells were labeled with calcein and MSC with DiO, MSC gained calcein while HL-1 cells gained DiO. Very little fusion was observed since more than 90% Sca-1 positive MSC gained DiO from HL-1 cells while less than 9% gained gap junction impermeant CMFDA after 20 hours with no Sca-1 transfer to HL-1 cells. Time dependent transfer of membrane DiD was observed from HL-1 cells to MSC (100%) and vice versa (50%) after 20 hours with more limited transfer of CMFDA. These results demonstrate that MSC and HL-1 cells exchange membrane components which may account for some of the beneficial effect of MSC in the heart after myocardial infarction.

Design, synthesis, and biological evaluation of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives as anti-proliferative agents through ROS-induced cell apoptosis.

PubMed

Song, Zhuang; Chen, Cai-Ping; Liu, Jun; Wen, Xiaoan; Sun, Hongbin; Yuan, Haoliang

2016-11-29

A novel class of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives were designed and synthesized as potent anti-proliferative agents. Most of these compounds showed potent anti-proliferative activity against some tumor cell lines, including SK-BR-3, MDA-MB-231, HCT-116, SW480, Ovcar-3, HL-60, Saos-2 and HepG2. Compounds 8c and 11h were identified as the most potent ones, while HL-60, HCT116 and MDA-MB-231 were the most sensitive cell lines. Mechanistic study revealed that compound 8c enhanced reactive oxygen species level by inhibiting TrxR and then induced apoptosis by activating apoptosis proteins, bax and cleaved-caspase 3 in HCT116 cells. Preliminary SAR analysis indicated that modifications of the double bond and ester group made great effects on the anti-proliferative activity. Our findings suggested that it was worth further studies on the antitumor potency of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetates. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Standards to support information systems integration in anatomic pathology.

PubMed

Daniel, Christel; García Rojo, Marcial; Bourquard, Karima; Henin, Dominique; Schrader, Thomas; Della Mea, Vincenzo; Gilbertson, John; Beckwith, Bruce A

2009-11-01

Integrating anatomic pathology information- text and images-into electronic health care records is a key challenge for enhancing clinical information exchange between anatomic pathologists and clinicians. The aim of the Integrating the Healthcare Enterprise (IHE) international initiative is precisely to ensure interoperability of clinical information systems by using existing widespread industry standards such as Digital Imaging and Communication in Medicine (DICOM) and Health Level Seven (HL7). To define standard-based informatics transactions to integrate anatomic pathology information to the Healthcare Enterprise. We used the methodology of the IHE initiative. Working groups from IHE, HL7, and DICOM, with special interest in anatomic pathology, defined consensual technical solutions to provide end-users with improved access to consistent information across multiple information systems. The IHE anatomic pathology technical framework describes a first integration profile, "Anatomic Pathology Workflow," dedicated to the diagnostic process including basic image acquisition and reporting solutions. This integration profile relies on 10 transactions based on HL7 or DICOM standards. A common specimen model was defined to consistently identify and describe specimens in both HL7 and DICOM transactions. The IHE anatomic pathology working group has defined standard-based informatics transactions to support the basic diagnostic workflow in anatomic pathology laboratories. In further stages, the technical framework will be completed to manage whole-slide images and semantically rich structured reports in the diagnostic workflow and to integrate systems used for patient care and those used for research activities (such as tissue bank databases or tissue microarrayers).

Evaluation of health literacy among Spanish-speaking primary care patients along the US--Mexico border.

PubMed

Penaranda, Eribeth; Diaz, Marco; Noriega, Oscar; Shokar, Navkiran

2012-07-01

Health literacy (HL) is a measure of the communication skills that are needed by an individual to effectively navigate the healthcare system. Hispanic adults have lower average levels of HL than any other racial/ethnic group; however, the prevalence of adequate HL among Hispanics along the US-Mexico border is unknown. We performed a cross-sectional survey of 200 adult primary care patients who attended four low-income community clinics along the US-Mexico border. Patients were included in the study if they were self-described Hispanics whose first language was Spanish or bilingual patients who reported that they were primarily Spanish speakers. Adequate HL was defined as having a score of ≥38 on the Short Assessment of Health Literacy for Spanish Adults-50. Three patients (1.5%) had inadequate HL. Because of the high proportion of patients having adequate HL, we found no statistical differences between patients with adequate HL versus inadequate HL by age, sex, educational attainment, health coverage, or self-reported health status; however, all three patients with inadequate HL were found to be 60 years old or older and had less than a high school education. The results of HL assessment varied according to the tool and setting used in measuring Spanish-speaking Hispanics. In certain clinical scenarios, current tools may underestimate the actual prevalence of adequate HL. Further development and assessment of HL tools appropriate for Spanish-speaking Hispanics is needed as a first step in developing interventions to limit disparities in health care among all Americans.

"Why do you want your child to have braces?" Investigating the motivations of Hispanic/Latino and white parents.

PubMed

Davis, Blake B; Bayirli, Burcu; Ramsay, Douglas S; Turpin, David L; Paige, Andrew; Riedy, Christine A

2015-11-01

Many psychological, social, and cultural factors influence parents' motivation to seek orthodontic care for their children. In this study, we used Q methodology to identify and categorize shared motives and determine whether cultural differences exist between Hispanic/Latino (H/L) and non-Hispanic/Latino, white (W) parents. The fundamental question posed to the parents was "Why do you want your child to have braces?" Q methodology involves 3 stages. (1) Interviews of H/L (n = 5) and W (n = 5) parents generated 35 statements that represented different motives to seek orthodontic care. (2) In the Q sort, 70 new parents (22 H/L, 48 W) ranked statements in order of relative importance using a forced distribution grid. (3) Factor analysis was performed separately for the H/L and W groups to uncover cultural differences. Four motivational profiles were described for both the H/L and W parents based on the significant factors identified in each group. More H/L parents (18 of 22 parents) than W parents (22 of 48 parents) were characterized by 1 of their group's 4 profiles. Comparisons of the motivational profiles across the groups showed 4 global themes: well-timed treatment that prevents future dental problems, parental responsibility, perceived benefits, and perceived need instilled by the dentist. Four global themes captured the motives of most parents seeking orthodontic treatment for their children. Understanding these global themes can help clinicians frame their treatment discussions with parents. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Analysis of wave III of brain stem auditory evoked potential waveforms during microvascular decompression of cranial nerve VII for hemifacial spasm.

PubMed

Thirumala, Parthasarathy D; Krishnaiah, Balaji; Crammond, Donald J; Habeych, Miguel E; Balzer, Jeffrey R

2014-04-01

Intraoperative monitoring of brain stem auditory evoked potential during microvascular decompression (MVD) prevent hearing loss (HL). Previous studies have shown that changes in wave III (wIII) are an early and sensitive sign of auditory nerve injury. To evaluate the changes of amplitude and latency of wIII of brain stem auditory evoked potential during MVD and its association with postoperative HL. Hearing loss was classified by American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) criteria, based on changes in pure tone audiometry and speech discrimination score. Retrospective analysis of wIII in patients who underwent intraoperative monitoring with brain stem auditory evoked potential during MVD was performed. A univariate logistic regression analysis was performed on independent variables amplitude of wIII and latency of wIII at change max and On-Skin, or a final recording at the time of skin closure. A further analysis for the same variables was performed adjusting for the loss of wave. The latency of wIII was not found to be significantly different between groups I and II. The amplitude of wIII was significantly decreased in the group with HL. Regression analysis did not find any increased odds of HL with changes in the amplitude of wIII. Changes in wave III did not increase the odds of HL in patients who underwent brain stem auditory evoked potential s during MVD. This information might be valuable to evaluate the value of wIII as an alarm criterion during MVD to prevent HL.

The Impact of Health Literacy Status on the Comparative Validity and Sensitivity of an Interactive Multimedia Beverage Intake Questionnaire.

PubMed

Hooper, Lucy P; Myers, Emily A; Zoellner, Jamie M; Davy, Brenda M; Hedrick, Valisa E

2016-12-23

Self-reported dietary assessment methods can be challenging to validate, and reporting errors for those with lower health literacy (HL) may be augmented. Interactive multimedia (IMM) based questionnaires could help overcome these limitations. The objectives of this investigation are to assess the comparative validity and sensitivity to change of an IMM beverage intake questionnaire (IMM-BEVQ) as compared to dietary recalls and determine the impact of HL. Adults completed three 24-h dietary recalls and the IMM-BEVQ at baseline and after a six-month intervention targeting either sugar-sweetened beverages (SSB) or physical activity. Correlations and paired-samples t -tests are presented. For validity ( n = 273), intake of SSB (mean difference = 10.6 fl oz) and total beverage consumption (mean difference = 16.0 fl oz) were significantly different ( p ≤ 0.001) at baseline between the IMM-BEVQ and dietary recalls for all participants. However, the differences in intake were generally greater in low HL participants than in adequate HL participants. For sensitivity ( n = 162), change in SSB intake (mean difference = 7.2 fl oz) was significantly different ( p ≤ 0.01) between pre-/post-IMM-BEVQ and pre-/post-dietary recalls, but not total beverage intake (mean difference = 7.6 fl oz) for all participants. Changes in SSB and total beverage intake were not significantly different for those with adequate HL. The IMM-BEVQ is a valid dietary assessment tool that is as responsive to detecting changes in beverage intake as dietary recalls. However, adults with lower HL may need additional guidance when completing the IMM-BEVQ.

Maturation of hepatic lipase. Formation of functional enzyme in the endoplasmic reticulum is the rate-limiting step in its secretion.

PubMed

Ben-Zeev, Osnat; Doolittle, Mark H

2004-02-13

Among three lipases in the lipase gene family, hepatic lipase (HL), lipoprotein lipase, and pancreatic lipase, HL exhibits the lowest intracellular specific activity (i.e. minimal amounts of catalytic activity accompanied by massive amounts of inactive lipase mass in the endoplasmic reticulum (ER)). In addition, HL has a distinctive sedimentation profile, where the inactive mass overlaps the region containing active dimeric HL and trails into progressively larger molecular forms. Eventually, at least half of the HL inactive mass in the ER reaches an active, dimeric conformation (t(1/2) = 2 h) and is rapidly secreted. The remaining inactive mass is degraded. HL maturation occurs in the ER and is strongly dependent on binding to calnexin in the early co-/post-translational stages. Later stages of HL maturation occur without calnexin assistance, although inactive HL at all stages appears to be associated in distinct complexes with other ER proteins. Thus, unlike other lipases in the gene family, HL maturation is the rate-limiting step in its secretion as a functional enzyme.

A novel C-type lectin with triple carbohydrate recognition domains has critical roles for the hard tick Haemaphysalis longicornis against Gram-negative bacteria.

PubMed

Maeda, Hiroki; Miyata, Takeshi; Kusakisako, Kodai; Galay, Remil Linggatong; Talactac, Melbourne Rio; Umemiya-Shirafuji, Rika; Mochizuki, Masami; Fujisaki, Kozo; Tanaka, Tetsuya

2016-04-01

C-type lectins (CLecs) play an important role in innate immunity against invaders. In this study, a novel CLec was identified from Haemaphysalis longicornis ticks (HlCLec). HlCLec contains a signal peptide and a transmembrane region. Interestingly, HlCLec possesses three dissimilar carbohydrate recognition domains (CRDs). Each CRD contains the mutated motif of Ca(2+)-binding site 2. HlCLec mRNA was up-regulated during blood feeding, and had highest expression in the midgut and ovary. HlCLec localization was also confirmed by immunofluorescent antibody test (IFAT). HlCLec was found on the cell membrane and basal lamina of midgut and ovary. In addition, the recombinant HlCLec and individual CRDs demonstrated direct binding activity to Escherichia coli and Staphylococcus aureus; however, no growth inhibition activity was observed. Furthermore, E. coli injection after silencing of HlCLec caused drastic reduction in survival rate of ticks. These results strongly suggest the key role of HlCLec in tick innate immunity against Gram-negative bacteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lipase-catalyzed preparation of optically active 1'-acetoxychavicol acetates and their structure-activity relationships in apoptotic activity against human leukemia HL-60 cells.

PubMed

Azuma, Hideki; Miyasaka, Keita; Yokotani, Tsuyoshi; Tachibana, Taro; Kojima-Yuasa, Akiko; Matsui-Yuasa, Isao; Ogino, Kenji

2006-03-15

Structure-activity relationships of 1'-acetoxychavicol acetate (ACA) for apoptotic activity against human leukemia HL-60 cells were investigated using optically active ACA and various racemic ACA analogues. Natural-type (or with different acyl group) ACA showed a high apoptotic activity, but the ortho or meta isomers, 4-deacetoxy analogue, and the 2'-3' dehydrogenated derivative had no effect, or a weak activity. Optically active (R)- and (S)-ACA were prepared by a lipase-catalyzed esterification. Using a mixture of vinyl acetate-tetrahydrofuran (1:1 v/v) as a solvent at refluxing temperature, optically pure (R)- and (S)-ACA were obtained (99.7% ee and 99.1% ee, respectively). The apoptosis-inducing effects of both enantiomers were compared by means of an MTT assay and the detection of typical apoptotic phenomena (DNA fragmentation, caspase-3 activation, and PARP cleavage) and these two activities were almost equal. These results indicate that the essential moieties of ACA for apoptotic activity against HL-60 cells are both the presence of a 4-acetoxyl group and an unsaturated double bond between C-2' and C-3', and that the configuration at the 1'-position is unrelated to activity.

Rheumatoid arthritis and lymphoma: Incidence, pathogenesis, biology, and outcome.

PubMed

Klein, Alina; Polliack, Aaron; Gafter-Gvili, Anat

2018-06-03

Patients with rheumatoid arthritis (RA) have a greater risk of developing both Hodgkin lymphoma (HL) and non-HL than the general population. Non-Hodgkin lymphoma is more common than HL in these patients, and diffuse large B cell lymphoma is the most frequent subtype observed. Although the clinical course of lymphoma in RA is often aggressive, the prognosis in these cases is similar to that of lymphoma in the general population. In this review, we summarize data derived from both retrospective and prospective studies, regarding incidence, pathogenesis, and outcome of lymphomas in RA patients and outline the possible mechanisms and hypotheses linking these 2 disorders. Over the years, 3 main theories have been suggested to explain this association. These hypotheses relate to genetic predisposition, persistence of long standing disease activity with continued immune stimulation, and the role of anti-RA therapy given. A common genetic predisposition linking RA and lymphoma has not been established. As for treatment of RA, this includes immunosuppressive antitumor necrosis factor drugs or conventional disease modifying antirheumatic drugs like methotrexate. Neither of these drug categories appears to be associated with a higher risk of lymphoma in RA. The impact of continuing disease activity and immune stimulation appears to be the most significant in lymphomagenesis in these patients. Copyright © 2018 John Wiley & Sons, Ltd.

Magnetic Frequency Response of HL-LHC Beam Screens

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

Morrone, M.; Martino, M.; De Maria, R.

Magnetic fields used to control particle beams in accelerators are usually controlled by regulating the electrical current of the power converters. In order to minimize lifetime degradation and ultimately luminosity loss in circular colliders, current-noise is a highly critical figure of merit of power converters, in particular for magnets located in areas with high beta-function, like the High Luminosity Large Hadron Collider (HL-LHC) insertions. However, what is directly acting upon the beam is the magnetic field and not the current of the power converter, which undergoes several frequency-dependent transformations until the desired magnetic field, seen by the beam, is obtained.more » Beam screens are very rarely considered when assessing or specifying the noise figure of merit, but their magnetic frequency response is such that they realize relatively effective low pass filtering of the magnetic field produced by the system magnet-power converter. This work aims at filling this gap by quantifying the expected impact of different beam screen layouts for the most relevant HL-LHC insertion magnets. A welldefined post-processing technique is used to derive the frequency response of the different multipoles from multi-physics Finite Element Method (FEM) simulation results. In addition, a well approximated analytical formula for the low-frequency range of multi-layered beam screens is presented.« less

Intermedin A, a New Labdane Diterpene Isolated from Alpinia intermedia, Prolonged the Survival Time of P-388D1 Tumor-Bearing CDF1 Mice.

PubMed

Chen, Lih-Geeng; Su, Pei-Jung; Tsai, Po-Wei; Yang, Ling-Ling; Wang, Ching-Chiung

2017-01-01

Eight ethanolic extracts of indigenous Taiwanese plants of the genus Alpinia were tested for tumor cytotoxicity against AGS, Hep G2, HeLa, KB, and HL-60 cells. Among the 50 % and 95 % EtOH extracts of eight Alpinia species, the cytotoxic effects of Alpinia intermedia leaves were the strongest. When the leaf extract of A. intermedia was partitioned using n -hexane and aqueous solvents, the n -hexane layer showed a greater cytotoxic effect and could prolong the survival time of P-388D 1 tumor-bearing CDF1 mice. Two new labdane diterpene derivatives, intermedin A ( 1 ) and intermedin B ( 2 ), and coronarin E ( 3 ) were isolated from the n -hexane layer of A. intermedia . Intermedin A induced apoptosis in HL-60 cells at 30 µg/mL and significantly prolonged the survival time of P-388D 1 tumor-bearing CDF 1 mice by 48.7 % at 20 mg/kg of body weight. We suggest that intermedin A is a major compound of A. intermedia and has a cytotoxic effect on HL-60 and P-388D 1 cells. Georg Thieme Verlag KG Stuttgart · New York.

Synthesis, structural characterization, and pro-apoptotic activity of 1-indanone thiosemicarbazone platinum(II) and palladium(II) complexes: potential as antileukemic agents.

PubMed

Gómez, Natalia; Santos, Diego; Vázquez, Ramiro; Suescun, Leopoldo; Mombrú, Alvaro; Vermeulen, Monica; Finkielsztein, Liliana; Shayo, Carina; Moglioni, Albertina; Gambino, Dinorah; Davio, Carlos

2011-08-01

In the search for alternative chemotherapeutic strategies against leukemia, various 1-indanone thiosemicarbazones, as well as eight novel platinum(II) and palladium(II) complexes, with the formula [MCl₂(HL)] and [M(HL)(L)]Cl, derived from two 1-indanone thiosemicarbazones were synthesized and tested for antiproliferative activity against the human leukemia U937 cell line. The crystal structure of [Pt(HL1)(L1)]Cl·2MeOH, where L1=1-indanone thiosemicarbazone, was solved by X-ray diffraction. Free thiosemicarbazone ligands showed no antiproliferative effect, but the corresponding platinum(II) and palladium(II) complexes inhibited cell proliferation and induced apoptosis. Platinum(II) complexes also displayed selective apoptotic activity in U937 cells but not in peripheral blood monocytes or the human hepatocellular carcinoma HepG2 cell line used to screen for potential hepatotoxicity. Present findings show that, in U937 cells, 1-indanone thiosemicarbazones coordinated to palladium(II) were more cytotoxic than those complexed with platinum(II), although the latter were found to be more selective for leukemic cells suggesting that they are promising compounds with potential therapeutic application against hematological malignancies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessment of medication adherence app features, functionality, and health literacy level and the creation of a searchable Web-based adherence app resource for health care professionals and patients.

PubMed

Heldenbrand, Seth; Martin, Bradley C; Gubbins, Paul O; Hadden, Kristie; Renna, Catherine; Shilling, Rebecca; Dayer, Lindsey

2016-01-01

To assess the features and level of health literacy (HL) of available medication adherence apps and to create a searchable website to assist health care providers (HCP) and patients identify quality adherence apps. Medication nonadherence continues to be a significant problem and leads to poor health outcomes and avoidable health care expense. The average adherence rate for chronic medications, regardless of disease state, is approximately 50% leaving significant room for improvement. Smartphone adherence apps are a novel resource to address medication nonadherence. With widespread smartphone use and the growing number of adherence apps, both HCP and patients should be able to identify quality adherence apps to maximize potential benefits. Assess the features, functionality and level of HL of available adherence apps and create a searchable website to help both HCP and patients identify quality adherence apps. Online marketplaces (iTunes, Google Play, Blackberry) were searched in June of 2014 to identify available adherence apps. Online descriptions were recorded and scored based on 28 author-identified features across 4 domains. The 100 highest-scoring apps were user-tested with a standardized regimen to evaluate their functionality and level of HL. 461 adherence apps were identified. 367 unique apps were evaluated after removing "Lite/Trial" versions. The median initial score based on descriptions was 15 (max of 68; range: 3 to 47). Only 77 apps of the top 100 highest-scoring apps completed user-testing and HL evaluations. The median overall user-testing score was 30 (max of 73; range: 16 to 55). App design, functionality, and level of HL varies widely among adherence apps. While no app is perfect, several apps scored highly across all domains. The website www.medappfinder.com is a searchable tool that helps HCP and patients identify quality apps in a crowded marketplace. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

HL-10 after landing with pilot Bill Dana

NASA Technical Reports Server (NTRS)

1960-01-01

This movie clip, running about 56 seconds, shows NASA pilot Bill Dana exiting the cockpit of the HL-10 and waving to his B-52 drop aircraft, just after landing on the dry lakebed at Edwards Air Force Base, California. A fleet of lifting bodies flown at the NASA Flight Research Center, Edwards, California, from 1963 to l975 demonstrated the ability of pilots to maneuver (in the atmosphere) and safely land a wingless vehicle. These lifting bodies were basically designed so they could fly back to Earth from space and be landed like an aircraft at a pre-determined site. (In 1976 NASA renamed the FRC as the NASA Dryden Flight Research Center in honor of Hugh L. Dryden.) These unique research vehicles, with their unconventional aerodynamic shapes, were the M2-F1, M2-F2, M2-F3, HL-10, X-24A, and the X-24B. The information the lifting body program generated contributed to the database that led to development of the current space shuttle program as well as the X-33 and X-38 technology demonstrators. Aerodynamic lift -- essential to flight in the atmosphere -- was obtained from the shape of the vehicles rather than from wings on a normal aircraft. The addition of fins and control surfaces allowed the pilots to stabilize and control the vehicles and regulate their flight paths. All but the M2-F1 were powered by the same type of XLR-11 rocket engine used in the famed Bell X-1 -- first aircraft to fly faster than the speed of sound. The M2-F1, a lightweight prototype, was unpowered. The success of the Dryden M2-F1 program led to the NASA development and construction of two heavyweight lifting bodies based on studies at NASA Ames and Langley research centers -- the M2-F2 and the HL-10, both built by the Northrop Corporation. The 'M' refers to 'manned' and 'F' refers to 'flight' version. 'HL' comes from 'horizontal landing' and '10' is for the tenth lifting body model to be investigated by Langley Research Center, Hampton, Virginia. The HL-10 was delivered to the FRC by Northrop in January 1966. Its first flight was on December 22 of the same year. The pilot was Bruce Peterson, before he was injured in the M2-F2 accident. The HL-10 was flown 37 times and it set several program records. On Feb. 18, 1970, Air Force test pilot Major Peter Hoag flew it to 1,228 m.p.h. (Mach 1.86), fastest speed of any of the lifting bodies. Nine days later, NASA pilot Bill Dana flew the HL-10 to 90,303 feet, the highest altitude reached by any of the lifting body vehicles. The HL-10 was also the first lifting body to fly supersonically -- on May 9, 1969, with NASA pilot John Manke at the controls. The HL-10 featured a flat bottom and rounded top -- much like an airfoil -- and it had a delta planform. In its final configuration, three vertical fins, two of them canted outwards from the body and a tall center fin, gave the craft directional control. A flush canopy blended into the smooth rounded nose. It was about 21 feet long, with a span of 13.6 feet. Its glide-flight weight was 6,473 pounds and its maximum gross weight was over 10,000 pounds. Flights with the HL-10 contributed substantially to the decision to design the space shuttles without air-breathing engines that would have been used for landings. Its final flight was on July 17, 1970. The HL-10 is now on public display at Dryden.

Novel pyrrole derivatives bearing sulfonamide groups: Synthesis in vitro cytotoxicity evaluation, molecular docking and DFT study

NASA Astrophysics Data System (ADS)

Bavadi, Masoumeh; Niknam, Khodabakhsh; Shahraki, Omolbanin

2017-10-01

The synthesis of new derivatives of pyrrole substituted sulfonamide groups is described. The in vitro anticancer activity of these pyrroles was evaluated against MCF7, MOLT-4 and HL-60 cells using MTT assay. The target compounds showed inhibitory activity against tested cell lines. Among the compounds, compound 1a exhibited good cytotoxic activity. The potential of this analog to induce apoptosis was confirmed in a nuclear morphological assay by Hoechst 33258 staining in the PC-12 cells. Finally, molecular docking was performed to determine the probable binding mode of the designed pyrrole derivatives into the active site of FGFR1 protein. DFT calculations were carried out at the B3LYP levels of theory with 6-31+G (d,p) basis set for compound 1a. The point group (C1) of it was obtained based on the optimized structures; the calculation of the FT-IR vibrational frequencies, 1H NMR and 13C NMR chemical shifts of the compound were carried out and compared with those obtained experimentally.

Guanidinium-based derivatives: searching for new kinase inhibitors.

PubMed

Diez-Cecilia, Elena; Kelly, Brendan; Perez, Concepcion; Zisterer, Daniela M; Nevin, Daniel K; Lloyd, David G; Rozas, Isabel

2014-06-23

Considering the structural similarities between the kinase inhibitor sorafenib and 4,4'-bis-guanidinium derivatives previously prepared by Rozas and co., which display interesting cytotoxicity in cancer cells, we have studied whether this activity could result from kinase inhibition. Five new families have been prepared consisting of unsubstituted and aryl-substituted 3,4'-bis-guanidiniums, 3,4'-bis-2-aminoimidazolinium and 3-acetamide-4'-(4-chloro-3-trifluoromethylphenyl)guanidinium derivatives. Cytotoxicity (measuring the IC50 values) and apoptosis studies in human HL-60 promyelocytic leukemia cells were carried out for these compounds. Additionally, their potential inhibitory effect was explored on a panel of kinases known to be involved in apoptotic pathways. The previously prepared cytotoxic 4,4'-bis-guanidiniums did not inhibit any of these kinases; however, some of the novel 3,4'-substituted derivatives showed a high percentage inhibition of RAF-1/MEK-1, for which the potential mode of binding was evaluated by docking studies. The interesting antitumour properties showed by these compounds open up new exciting lines of investigation for kinase inhibitors as anticancer agents and also highlights the relevance of the guanidinium moiety for protein kinase inhibitors chemical design. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Lymphoma occurring during pregnancy: antenatal therapy, complications, and maternal survival in a multicenter analysis.

PubMed

Evens, Andrew M; Advani, Ranjana; Press, Oliver W; Lossos, Izidore S; Vose, Julie M; Hernandez-Ilizaliturri, Francisco J; Robinson, Barrett K; Otis, Stavroula; Nadav Dagan, Liat; Abdallah, Ramsey; Kroll-Desrosiers, Aimee; Yarber, Jessica L; Sandoval, Jose; Foyil, Kelley; Parker, Linda M; Gordon, Leo I; Blum, Kristie A; Flowers, Christopher R; Leonard, John P; Habermann, Thomas M; Bartlett, Nancy L

2013-11-10

Lymphoma is the fourth most frequent cancer in pregnancy; however, current clinical practice is based largely on small series and case reports. In a multicenter retrospective analysis, we examined treatment, complications, and outcomes for Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) occurring during pregnancy. Among 90 patients (NHL, n = 50; HL, n = 40), median age was 30 years (range, 18 to 44 years) and median diagnosis occurred at 24 weeks gestation. Of patients with NHL, 52% had advanced-stage versus 25% of patients with HL (P = .01). Pregnancy was terminated in six patients. Among the other 84 patients, 28 (33%) had therapy deferred to postpartum; these patients were diagnosed at a median 30 weeks gestation. This compared with 56 patients (67%) who received antenatal therapy with median lymphoma diagnosis at 21 weeks (P < .001); 89% of these patients received combination chemotherapy. The most common preterm complication was induction of labor (33%). Gestation went to full term in 56% of patients with delivery occurring at a median of 37 weeks. There were no differences in maternal complications, perinatal events, or median infant birth weight based on deferred versus antenatal therapy. At 41 months, 3-year progression-free survival (PFS) and overall survival (OS) for NHL were 53% and 82%, respectively, and 85% and 97%, respectively, for HL. On univariate analysis for NHL, radiotherapy predicted inferior PFS, and increased lactate dehydrogenase and poor Eastern Cooperative Oncology Group performance status (ECOG PS) portended worse OS. For HL patients, nulliparous status and "B" symptoms predicted inferior PFS. Standard (non-antimetabolite) combination chemotherapy administered past the first trimester, as early as 13 weeks gestation, was associated with few complications and expected maternal survival with lymphoma occurring during pregnancy.

Intercomparison of Streamflow Simulations between WRF-Hydro and Hydrology Laboratory-Research Distributed Hydrologic Model Frameworks

NASA Astrophysics Data System (ADS)

KIM, J.; Smith, M. B.; Koren, V.; Salas, F.; Cui, Z.; Johnson, D.

2017-12-01

The National Oceanic and Atmospheric Administration (NOAA)-National Weather Service (NWS) developed the Hydrology Laboratory-Research Distributed Hydrologic Model (HL-RDHM) framework as an initial step towards spatially distributed modeling at River Forecast Centers (RFCs). Recently, the NOAA/NWS worked with the National Center for Atmospheric Research (NCAR) to implement the National Water Model (NWM) for nationally-consistent water resources prediction. The NWM is based on the WRF-Hydro framework and is run at a 1km spatial resolution and 1-hour time step over the contiguous United States (CONUS) and contributing areas in Canada and Mexico. In this study, we compare streamflow simulations from HL-RDHM and WRF-Hydro to observations from 279 USGS stations. For streamflow simulations, HL-RDHM is run on 4km grids with the temporal resolution of 1 hour for a 5-year period (Water Years 2008-2012), using a priori parameters provided by NOAA-NWS. The WRF-Hydro streamflow simulations for the same time period are extracted from NCAR's 23 retrospective run of the NWM (version 1.0) over CONUS based on 1km grids. We choose 279 USGS stations which are relatively less affected by dams or reservoirs, in the domains of six different RFCs. We use the daily average values of simulations and observations for the convenience of comparison. The main purpose of this research is to evaluate how HL-RDHM and WRF-Hydro perform at USGS gauge stations. We compare daily time-series of observations and both simulations, and calculate the error values using a variety of error functions. Using these plots and error values, we evaluate the performances of HL-RDHM and WRF-Hydro models. Our results show a mix of model performance across geographic regions.

Using features of Arden Syntax with object-oriented medical data models for guideline modeling.

PubMed

Peleg, M; Ogunyemi, O; Tu, S; Boxwala, A A; Zeng, Q; Greenes, R A; Shortliffe, E H

2001-01-01

Computer-interpretable guidelines (CIGs) can deliver patient-specific decision support at the point of care. CIGs base their recommendations on eligibility and decision criteria that relate medical concepts to patient data. CIG models use expression languages for specifying these criteria, and define models for medical data to which the expressions can refer. In developing version 3 of the GuideLine Interchange Format (GLIF3), we used existing standards as the medical data model and expression language. We investigated the object-oriented HL7 Reference Information Model (RIM) as a default data model. We developed an expression language, called GEL, based on Arden Syntax's logic grammar. Together with other GLIF constructs, GEL reconciles incompatibilities between the data models of Arden Syntax and the HL7 RIM. These incompatibilities include Arden's lack of support for complex data types and time intervals, and the mismatch between Arden's single primary time and multiple time attributes of the HL7 RIM.

Quantitative Analysis of Global Proteome and Lysine Acetylome Reveal the Differential Impacts of VPA and SAHA on HL60 Cells.

PubMed

Zhu, Xiaoyu; Liu, Xin; Cheng, Zhongyi; Zhu, Jun; Xu, Lei; Wang, Fengsong; Qi, Wulin; Yan, Jiawei; Liu, Ning; Sun, Zimin; Liu, Huilan; Peng, Xiaojun; Hao, Yingchan; Zheng, Nan; Wu, Quan

2016-01-29

Valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) are both HDAC inhibitors (HDACi). Previous studies indicated that both inhibitors show therapeutic effects on acute myeloid leukaemia (AML), while the differential impacts of the two different HDACi on AML treatment still remains elusive. In this study, using 3-plex SILAC based quantitative proteomics technique, anti-acetyllysine antibody based affinity enrichment, high resolution LC-MS/MS and intensive bioinformatic analysis, the quantitative proteome and acetylome in SAHA and VPA treated AML HL60 cells were extensively studied. In total, 5,775 proteins and 1,124 lysine acetylation sites were successfully obtained in response to VAP and SAHA treatment. It is found that VPA and SAHA treatment differently induced proteome and acetylome profiling in AML HL60 cells. This study revealed the differential impacts of VPA and SAHA on proteome/acetylome in AML cells, deepening our understanding of HDAC inhibitor mediated AML therapeutics.

In vitro antileukaemic activity of extracts from chokeberry (Aronia melanocarpa [Michx] Elliott) and mulberry (Morus alba L.) leaves against sensitive and multidrug resistant HL60 cells.

PubMed

Skupień, Katarzyna; Kostrzewa-Nowak, Dorota; Oszmiański, Jan; Tarasiuk, Jolanta

2008-05-01

The aim of the present study was to determine in vitro antileukaemic activities of extracts obtained from chokeberry (Aronia melanocarpa [Michx] Elliot) and mulberry (Morus alba L.) leaves against promyelocytic HL60 cell line and its multidrug resistant sublines exhibiting two different MDR phenotypes: HL60/VINC (overexpressing P-glycoprotein) and HL60/DOX (overexpressing MRP1 protein). It was found that the extracts from chokeberry and mulberry leaves were active against the sensitive leukaemic cell line HL60 and retained the in vitro activity against multidrug resistant sublines (HL60/VINC and HL60/DOX). The values of resistance factor (RF) found for these extracts were very low lying in the range 1.2-1.6.

Cytotoxicity of Vitex agnus-castus fruit extract and its major component, casticin, correlates with differentiation status in leukemia cell lines.

PubMed

Kikuchi, Hidetomo; Yuan, Bo; Nishimura, Yoshio; Imai, Masahiko; Furutani, Ryota; Kamoi, Saki; Seno, Misako; Fukushima, Shin; Hazama, Shingo; Hirobe, Chieko; Ohyama, Kunio; Hu, Xiao-Mei; Takagi, Norio; Hirano, Toshihiko; Toyoda, Hiroo

2013-12-01

We have demonstrated that an extract from the ripe fruit of Vitex agnus-castus (Vitex) exhibits cytotoxic activities against various types of solid tumor cells, whereas its effects on leukemia cells has not been evaluated to date. In this study, the effects of Vitex and its major component, casticin, on leukemia cell lines, HL-60 and U-937, were investigated by focusing on proliferation, induction of apoptosis and differentiation. Identification and quantitation by NMR spectroscopy showed that casticin accounted for approximate 1% weight of Vitex. Dose-dependent cytotoxicity of Vitex and casticin was observed in both cell lines, and HL-60 cells were more sensitive to the cytotoxicity of Vitex/casticin compared to U-937 cells. Furthermore, compared to unstimulated HL-60 cells, phorbol 12-myristate 13-acetate (PMA)- and 1,25-dihydroxyvitamin D₃ (VD₃)-differentiated HL-60 cells acquired resistance to Vitex/casticin based on the results from cell viability and apoptosis induction analysis. Since the HL-60 cell line is more immature than the U-937 cell line, these results suggested that the levels of cytotoxicity of Vitex/casticin were largely attributed to the degree of differentiation of leukemia cells; that is, cell lines with less differentiated phenotype were more susceptible than the differentiated ones. RT-PCR analysis demonstrated that PMA upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) in HL-60 cells, and that anti-ICAM-1 monoclonal antibody not only abrogated PMA-induced aggregation and adhesion of the cells but also restored its sensitivity to Vitex. These results suggested that ICAM-1 plays a crucial role in the acquired resistance in PMA-differentiated HL-60 cells by contributing to cell adhesion. These findings provide fundamental insights into the clinical application of Vitex/casticin for hematopoietic malignancy.

Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes.

PubMed

Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

2015-01-01

Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

Projected Effects of Radiation-Induced Cancers on Life Expectancy in Patients Undergoing CT Surveillance for Limited-Stage Hodgkin Lymphoma: A Markov Model.

PubMed

Lowry, Kathryn P; Turan, Ekin A; Eisenberg, Jonathan; Kong, Chung Y; Barnes, Jeffrey A; Pandharipande, Pari Vijay

2015-06-01

Patients with limited-stage Hodgkin lymphoma (HL) undergo frequent posttreatment surveillance CT examinations, raising concerns about the cumulative magnitude of radiation exposure. The purpose of this study was to project radiation-induced cancer risks relative to competing risks of HL and account for the differential timing of each. We adapted a previously developed Markov model to project lifetime mortality risks and life expectancy losses due to HL versus radiation-induced cancers in HL patients undergoing surveillance CT. In the base case, we modeled 35-year-old men and women undergoing seven CT examinations of the chest, abdomen, and pelvis over 5 years. Radiation-induced cancer risks and deaths for 17 organ systems were modeled using an organ-specific approach, accounting for specific anatomy exposed at CT. Cohorts of 20-, 50-, and 65-year-old men and women were evaluated in secondary analyses. Markov chain Monte Carlo methods were used to estimate the uncertainty of radiation risk projections. For 35-year-old adults, we projected 3324/100,000 (men) and 3345/100,000 (women) deaths from recurrent lymphoma and 245/100,000 (men, 95% uncertainty interval [UI]: 121-369) and 317/100,000 (women, 95% UI: 202-432) radiation-induced cancer deaths. Discrepancies in life expectancy losses between HL (428 days in men, 482 days in women) and radiation-induced cancers (11.6 days in men, [95% UI: 5.7-17.5], 15.6 days in women [95% UI: 9.8-21.4]) were proportionately greater because of the delayed timing of radiation-induced cancers relative to recurrent HL. Deaths and life expectancy losses from radiation-induced cancers were highest in the youngest cohorts. Given the low rate of radiation-induced cancer deaths associated with CT surveillance, modest CT benefits would justify its use in patients with limited-stage HL.

HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma

PubMed Central

Hjalgrim, Henrik; Rostgaard, Klaus; Johnson, Paul C. D.; Lake, Annette; Shield, Lesley; Little, Ann-Margaret; Ekstrom-Smedby, Karin; Adami, Hans-Olov; Glimelius, Bengt; Hamilton-Dutoit, Stephen; Kane, Eleanor; Taylor, G. Malcolm; McConnachie, Alex; Ryder, Lars P.; Sundstrom, Christer; Andersen, Paal Skytt; Chang, Ellen T.; Alexander, Freda E.; Melbye, Mads; Jarrett, Ruth F.

2010-01-01

A proportion of classical Hodgkin lymphoma (HL) is believed to be causally related to infection with the ubiquitous lymphotropic EBV. The determining factors for development of EBV-related HL remain poorly understood, but likely involve immunological control of the viral infection. Accordingly, markers of the HLA class I region have been associated with risk of EBV-related HL. To study the host genetic component of EBV-related HL further, we investigated the lymphoma's association with HLA-A*01 and HLA-A*02 simultaneously in the setting of infectious mononucleosis (IM), a risk factor for EBV-related HL, in a case-series analysis including 278 EBV-related and 656 EBV-unrelated cases of HL. By logistic regression, HLA-A*01 alleles [odds ratio (OR) per allele, 2.15; 95% CI, 1.60–2.88] were associated with increased and HLA-A*02 alleles (OR per allele, 0.70; 95% CI, 0.51–0.97) with decreased risk of EBV-related HL. These allele-specific associations corresponded to nearly 10-fold variation in risk of EBV-related HL between HLA-A*01 and HLA-A*02 homozygotes. History of IM was also associated with risk of EBV-related HL (OR, 3.40; 95% CI, 1.74–6.66). The association between history of IM and EBV-related HL was not seen in the presence of HLA-A*02 because this allele appeared to neutralize the effect of IM on EBV-related HL risk. Our findings suggest that HLA class I-restricted EBV-specific cytotoxic T-cell responses and events in the early immune response to EBV infection in IM play critical roles in the pathogenesis of EBV-related HL. PMID:20308568

HL-A27 and anterior uveitis.

PubMed

Woodrow, J C; Mapstone, R; Anderson, J; Usher, N

1975-09-01

HL-A types were determined in 90 successive patients with non-granulomatous uveitis. Fifty-one were HL-A27 positive (55.7%) compared to 8.2% of controls. Of 16 patients with ankylosing spondylitis, 13 were HL-A27 positive, as were two patients with a history of Reiter's syndrome. Twenty-eight patients were HL-A27 positive but had no evidence of rheumatic disease. The findings are discussed in relation to the possible pathogenesis of uveitis.

Footwear used by older people and a history of hyperkeratotic lesions on the foot

PubMed Central

Palomo-López, Patricia; Becerro-de-Bengoa-Vallejo, Ricardo; Losa-Iglesias, Marta Elena; Rodríguez-Sanz, David; Calvo-Lobo, César; López-López, Daniel

2017-01-01

Abstract Inadequate footwear, painful and hyperkeratotic lesions (HL) are an extremely common problems amongst older people. Such problems increase the risk of falls, hamper mobility, reduction of quality of life, dignity, and ability to remain independent. The etiology of painful and feet conditions is poorly understood. To discover footwear preferences of older people, pain tolerance may favor presence of HL for the use of inadequate footwear in old age. A sample of 100 participants with a mean age of 74.90 ± 7.01 years attended an outpatient clinic where self-reported demographic data, frequency with which they checked their feet were recorded and measurements were taken of foot sensitivity. Additionally, all participants’ shoes were allocated into optimal, adequate, and dangerous categories based on design, structural and safety features, and materials. Only 12% of the sample population checked their feet every day, 37% revealed symptoms of neuropathy, 14% used optimal shoes, and 61% presented HL. In a bivariate analysis, no significant differences were observed. HL are associated with inadequate footwear, loss of sensitivity, and low frequency of foot health checks. PMID:28403112

Diterpenes from Xylopia langsdorffiana inhibit cell growth and induce differentiation in human leukemia cells.

PubMed

Castello Branco, Marianna V S; Anazetti, Maristella C; Silva, Marcelo S; Tavares, Josean F; Diniz, Margareth F F Melo; Frungillo, Lucas; Haun, Marcela; Melo, Patrícia S

2009-01-01

Two new diterpenes were isolated from stems and leaves of Xylopia langsdorffiana, ent-atisane-7alpha,16alpha-diol (xylodiol) and ent-7alpha-acetoxytrachyloban-18-oic acid (trachylobane), along with the known 8(17),12E,14-labdatrien-18-oic acid (labdane). We investigated their antitumour effects on HL60, U937 and K562 human leukemia cell lines. We found that xylodiol was the most potent diterpene in inhibiting cell proliferation of HL60, U937 and K562 cells, with mean IC50 values of 90, 80 and 50 microM, respectively. Based on the nitroblue tetrazolium (NBT) reduction assay, all the diterpenes were found to induce terminal differentiation in HL60 and K562 cells, with xylodiol being the most effective. NBT reduction was increased by almost 120% after 12 h exposure of HL60 cells to xylodiol at a concentration lower than the IC50 (50 microM). Thus, xylodiol inhibited human leukemia cell growth in vitro partly by inducing cell differentiation, and merits further studies to examine its mechanism of action as a potential antitumoural agent.

HL-20 operations and support requirements for the Personnel Launch System mission

NASA Technical Reports Server (NTRS)

Morris, W. D.; White, Nancy H.; Caldwell, Ronald G.

1993-01-01

The processing, mission planning, and support requirements were defined for the HL-20 lifting-body configuration that can serve as a Personnel Launch System. These requirements were based on the assumption of an operating environment that incorporates aircraft and airline support methods and techniques that are applicable to operations. The study covered the complete turnaround process for the HL-20, including landing through launch, and mission operations, but did not address the support requirements of the launch vehicle except for the integrated activities. Support is defined in terms of manpower, staffing levels, facilities, ground support equipment, maintenance/sparing requirements, and turnaround processing time. Support results were drawn from two contracted studies, plus an in-house analysis used to define the maintenance manpower. The results of the contracted studies were used as the basis for a stochastic simulation of the support environment to determine the sufficiency of support and the effect of variance on vehicle processing. Results indicate the levels of support defined for the HL-20 through this process to be sufficient to achieve the desired flight rate of eight flights per year.

Fluorometric detection of nitroaromatics by fluorescent lead complexes: A spectroscopic assessment of detection mechanism

NASA Astrophysics Data System (ADS)

Chattopadhyay, Tanmay; Chatterjee, Sourav; Majumder, Ishani; Ghosh, Soumen; Yoon, Sangee; Sim, Eunji

2018-04-01

Three Schiff base ligands such as 2-[(2-Hydroxy-3-methoxy-benzylidene)-amino]-2-hydroxymethyl-propane-1,3-diol (HL1), 2-[(2-Hydroxy-benzylidene)-amino]-2-hydroxymethyl-propane-1,3-diol (HL2), 2-[(3,5-Dichloro-2-hydroxy-benzylidene)-amino]-2-hydroxymethyl-propane-1,3-diol (HL3) have been synthesized by condensation of aldehydes (such as 3,5-Dichloro-2-hydroxy benzaldehyde, 2-Hydroxy-benzaldehyde, and 2-Hydroxy-3-methoxy-benzaldehyde) with Tris-(hydroxymethyl)amino methane and characterized by IR, UV-vis and 1H NMR spectroscopy. Then all these three ligands have been used to prepare Pb(II) complexes by reaction with lead(II) acetate tri-hydrate in methanol. In view of analytical and spectral (IR, UV-vis and Mass) studies, it has been concluded that, except HL2, other two ligands form 1:1 metal complexes (1 and 3) with lead. Between two complexes, complex 3 is highly fluorescent and this property has been used to identify the pollutant nitroaromatics. Finally, the quenching mechanism has been established by means of spectroscopic investigation.

C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro.

PubMed

Grebinyk, A; Prylutska, S; Grynyuk, I; Kolp, B; Hurmach, V; Sliva, T; Amirkhanov, V; Trush, V; Matyshevska, O; Slobodyanik, M; Prylutskyy, Yu; Frohme, M; Ritter, U

2018-03-09

New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C 60 fullerene.According to molecular simulation results, C 60 fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C 60 fullerene and DNA G nucleotide, as well as by interactions of HL CCl 3 group by ion-π bonds with C 60 molecule and by electrostatic bonds with DNA G nucleotide.With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC 50 value detected at 10 μM concentration at 72 h of cells treatment was shown. Under combined action of 16 μM C 60 fullerene and HL, the value of IC 50 was detected at lower 5 μM HL concentration and at earlier 48 h period of incubation, besides the cytotoxic effect of HL was observed at a low 2.5 μM concentration at which HL by itself had no influence on cell viability. Binding of C 60 fullerene and HL with minor DNA groove with formation of a stable complex is assumed to be one of the possible reasons of their synergistic inhibition of CCRF-CЕM cells proliferation.Application of C 60 fullerene in combination with 2.5 μM HL was shown to have no harmful effect on structural stability of blood erythrocytes membrane. Thus, combined action of C 60 fullerene and HL in a low concentration potentiated HL cytotoxic effect against human leukemic cells and was not followed by hemolytic effect.

C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro

NASA Astrophysics Data System (ADS)

Grebinyk, A.; Prylutska, S.; Grynyuk, I.; Kolp, B.; Hurmach, V.; Sliva, T.; Amirkhanov, V.; Trush, V.; Matyshevska, O.; Slobodyanik, M.; Prylutskyy, Yu.; Frohme, M.; Ritter, U.

2018-03-01

New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C60 fullerene. According to molecular simulation results, C60 fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C60 fullerene and DNA G nucleotide, as well as by interactions of HL CCl3 group by ion-π bonds with C60 molecule and by electrostatic bonds with DNA G nucleotide. With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC50 value detected at 10 μM concentration at 72 h of cells treatment was shown. Under combined action of 16 μM C60 fullerene and HL, the value of IC50 was detected at lower 5 μM HL concentration and at earlier 48 h period of incubation, besides the cytotoxic effect of HL was observed at a low 2.5 μM concentration at which HL by itself had no influence on cell viability. Binding of C60 fullerene and HL with minor DNA groove with formation of a stable complex is assumed to be one of the possible reasons of their synergistic inhibition of CCRF-CEM cells proliferation. Application of C60 fullerene in combination with 2.5 μM HL was shown to have no harmful effect on structural stability of blood erythrocytes membrane. Thus, combined action of C60 fullerene and HL in a low concentration potentiated HL cytotoxic effect against human leukemic cells and was not followed by hemolytic effect.

Designing of peptides with desired half-life in intestine-like environment.

PubMed

Sharma, Arun; Singla, Deepak; Rashid, Mamoon; Raghava, Gajendra Pal Singh

2014-08-20

In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life. In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides. In summary, this study describes a web server 'HLP' that has been developed for assisting scientific community for predicting intestinal half-life of peptides and to design mutant peptides with better half-life and physicochemical properties. HLP models were trained using a dataset of peptides whose half-lives have been determined experimentally in crude intestinal proteases preparation. Thus, HLP server will help in designing peptides possessing the potential to be administered via oral route (http://www.imtech.res.in/raghava/hlp/).

Convergence of Health Level Seven Version 2 Messages to Semantic Web Technologies for Software-Intensive Systems in Telemedicine Trauma Care.

PubMed

Menezes, Pedro Monteiro; Cook, Timothy Wayne; Cavalini, Luciana Tricai

2016-01-01

To present the technical background and the development of a procedure that enriches the semantics of Health Level Seven version 2 (HL7v2) messages for software-intensive systems in telemedicine trauma care. This study followed a multilevel model-driven approach for the development of semantically interoperable health information systems. The Pre-Hospital Trauma Life Support (PHTLS) ABCDE protocol was adopted as the use case. A prototype application embedded the semantics into an HL7v2 message as an eXtensible Markup Language (XML) file, which was validated against an XML schema that defines constraints on a common reference model. This message was exchanged with a second prototype application, developed on the Mirth middleware, which was also used to parse and validate both the original and the hybrid messages. Both versions of the data instance (one pure XML, one embedded in the HL7v2 message) were equally validated and the RDF-based semantics recovered by the receiving side of the prototype from the shared XML schema. This study demonstrated the semantic enrichment of HL7v2 messages for intensive-software telemedicine systems for trauma care, by validating components of extracts generated in various computing environments. The adoption of the method proposed in this study ensures the compliance of the HL7v2 standard in Semantic Web technologies.

Environmentally-Friendly Dense and Porous Geopolymers Using Fly Ash and Rice Husk Ash as Raw Materials

PubMed Central

Ziegler, Daniele; Formia, Alessandra; Tulliani, Jean-Marc; Palmero, Paola

2016-01-01

This paper assesses the feasibility of two industrial wastes, fly ash (FA) and rice husk ash (RHA), as raw materials for the production of geopolymeric pastes. Three typologies of samples were thus produced: (i) halloysite activated with potassium hydroxide and nanosilica, used as the reference sample (HL-S); (ii) halloysite activated with rice husk ash dissolved into KOH solution (HL-R); (iii) FA activated with the alkaline solution realized with the rice husk ash (FA-R). Dense and porous samples were produced and characterized in terms of mechanical properties and environmental impact. The flexural and compressive strength of HL-R reached about 9 and 43 MPa, respectively. On the contrary, the compressive strength of FA-R is significantly lower than the HL-R one, in spite of a comparable flexural strength being reached. However, when porous samples are concerned, FA-R shows comparable or even higher strength than HL-R. Thus, the current results show that RHA is a valuable alternative to silica nanopowder to prepare the activator solution, to be used either with calcined clay and fly ash feedstock materials. Finally, a preliminary evaluation of the global warming potential (GWP) was performed for the three investigated formulations. With the mix containing FA and RHA-based silica solution, a reduction of about 90% of GWP was achieved with respect to the values obtained for the reference formulation. PMID:28773587

Quantitative proteomic analysis of CMS-related changes in Honglian CMS rice anther.

PubMed

Sun, Qingping; Hu, Chaofeng; Hu, Jun; Li, Shaoqing; Zhu, Yingguo

2009-10-01

Honglian (HL) cytoplasmic male sterility (CMS) is one of the rice CMS types and has been widely used in hybrid rice production in China. The CMS line (Yuetai A, YTA) has a Yuetai B (maintainer line, YTB) nuclear genome, but has a rearranged mitochondrial (mt) genome consisting of Yuetai B. The fertility of hybrid (HL-6) was restored by restorer gene in nuclear genome of restorer line (9311). We used isotope-code affinity tag (ICAT) technology to perform the protein profiling of uninucleate stage rice anther and identify the CMS-HL related proteins. Two separate ICAT analyses were performed in this study: (1) anthers from YTA versus anthers from YTB, and (2) anthers from YTA versus anthers from HL-6. Based on the two analyses, a total of 97 unique proteins were identified and quantified in uninucleate stage rice anther under the error rate of less than 10%, of which eight proteins showed abundance changes of at least twofold between YTA and YTB. Triosephosphate isomerase, fructokinase II, DNA-binding protein GBP16 and ribosomal protein L3B were over-expressed in YTB, while oligopeptide transporter, floral organ regulator 1, kinase and S-adenosyl-L: -methionine synthetase were over-expressed in YTA. Reduction of the proteins associated with energy production and lesser ATP equivalents detected in CMS anther indicated that the low level of energy production played an important role in inducing CMS-HL.

Predicting High Health Care Resource Utilization in a Single-payer Public Health Care System: Development and Validation of the High Resource User Population Risk Tool (HRUPoRT).

PubMed

Rosella, Laura C; Kornas, Kathy; Yao, Zhan; Manuel, Douglas G; Bornbaum, Catherine; Fransoo, Randall; Stukel, Therese

2017-11-17

A large proportion of health care spending is incurred by a small proportion of the population. Population-based health planning tools that consider both the clinical and upstream determinants of high resource users (HRU) of the health system are lacking. To develop and validate the High Resource User Population Risk Tool (HRUPoRT), a predictive model of adults that will become the top 5% of health care users over a 5-year period, based on self-reported clinical, sociodemographic, and health behavioral predictors in population survey data. The HRUPoRT model was developed in a prospective cohort design using the combined 2005 and 2007/2008 Canadian Community Health Surveys (CCHS) (N=58,617), and validated using the external 2009/2010 CCHS cohort (N=28,721). Health care utilization for each of the 5 years following CCHS interview date were determined by applying a person-centered costing algorithm to the linked health administrative databases. Discrimination and calibration of the model were assessed using c-statistic and Hosmer-Lemeshow (HL) χ statistic. The best prediction model for 5-year transition to HRU status included 12 predictors and had good discrimination (c-statistic=0.8213) and calibration (HL χ=18.71) in the development cohort. The model performed similarly in the validation cohort (c-statistic=0.8171; HL χ=19.95). The strongest predictors in the HRUPoRT model were age, perceived general health, and body mass index. HRUPoRT can accurately project the proportion of individuals in the population that will become a HRU over 5 years. HRUPoRT can be applied to inform health resource planning and prevention strategies at the community level.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

The perspective of healthcare providers and patients on health literacy: a systematic review of the quantitative and qualitative studies.

PubMed

Rajah, Retha; Ahmad Hassali, Mohamed Azmi; Jou, Lim Ching; Murugiah, Muthu Kumar

2018-03-01

Health literacy (HL) is a multifaceted concept, thus understanding the perspective of healthcare providers, patients, and the system is vital. This systematic review examines and synthesises the available studies on HL-related knowledge, attitude, practice, and perceived barriers. CINAHL and Medline (via EBSCOhost), Google Scholar, PubMed, ProQuest, Sage Journals, and Science Direct were searched. Both quantitative and/or qualitative studies in the English language were included. Intervention studies and studies focusing on HL assessment tools and prevalence of low HL were excluded. The risk of biasness reduced with the involvement of two reviewers independently assessing study eligibility and quality. A total of 30 studies were included, which consist of 19 quantitative, 9 qualitative, and 2 mixed-method studies. Out of 17 studies, 13 reported deficiency of HL-related knowledge among healthcare providers and 1 among patients. Three studies showed a positive attitude of healthcare providers towards learning about HL. Another three studies demonstrated patients feel shame exposing their literacy and undergoing HL assessment. Common HL communication techniques reported practiced by healthcare providers were the use of everyday language, teach-back method, and providing patients with reading materials and aids, while time constraint was the most reported HL perceived barriers by both healthcare providers and patients. Significant gaps exists in HL knowledge among healthcare providers and patients that needs immediate intervention. Such as, greater effort placed in creating a health system that provides an opportunity for healthcare providers to learn about HL and patients to access health information with taking consideration of their perceived barriers.

A photophysical study of two fluorogen-activating proteins bound to their cognate fluorogens

NASA Astrophysics Data System (ADS)

Gaiotto, Tiziano; Nguyen, Hau B.; Jung, Jaemyeong; Gnanakaran, Gnana S.; Schmidt, Jurgen G.; Waldo, Geoffrey S.; Bradbury, Andrew M.; Goodwin, Peter M.

2011-03-01

We are exploring the use of fluorogen-activating proteins (FAPs) as reporters for single-molecule imaging. FAPs are single-chain antibodies selected to specifically bind small chromophoric molecules termed fluorogens. Upon binding to its cognate FAP the fluorescence quantum yield of the fluorogen increases giving rise to a fluorescent complex. Based on the seminal work of Szent-Gyorgyi et al. (Nature Biotechnology, Volume 26, Number 2, pp 235-240, 2008) we have chosen to study two fluorogen-activating single-chain antibodies, HL1.0.1-TO1 and H6-MG, bound to their cognate fluorogens, thiazole orange and malachite green derivatives, respectively. Here we use fluorescence correlation spectroscopy to study the photophysics of these fluorescent complexes.

Adult Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult Hodgkin lymphoma (HL) can be cured in over 75% of new cases with combination chemotherapy and/or radiation therapy. Subtypes include classical HL (nodular sclerosis mixed-cellularity, lymphocyte depletion, and lymphocyte-rich) and nodular lymphocyte–predominant HL. Get comprehensive information on HL and treatment in this clinician summary.

The Impact of Health Literacy Status on the Comparative Validity and Sensitivity of an Interactive Multimedia Beverage Intake Questionnaire

PubMed Central

Hooper, Lucy P.; Myers, Emily A.; Zoellner, Jamie M.; Davy, Brenda M.; Hedrick, Valisa E.

2016-01-01

Self-reported dietary assessment methods can be challenging to validate, and reporting errors for those with lower health literacy (HL) may be augmented. Interactive multimedia (IMM) based questionnaires could help overcome these limitations. The objectives of this investigation are to assess the comparative validity and sensitivity to change of an IMM beverage intake questionnaire (IMM-BEVQ) as compared to dietary recalls and determine the impact of HL. Adults completed three 24-h dietary recalls and the IMM-BEVQ at baseline and after a six-month intervention targeting either sugar-sweetened beverages (SSB) or physical activity. Correlations and paired-samples t-tests are presented. For validity (n = 273), intake of SSB (mean difference = 10.6 fl oz) and total beverage consumption (mean difference = 16.0 fl oz) were significantly different (p ≤ 0.001) at baseline between the IMM-BEVQ and dietary recalls for all participants. However, the differences in intake were generally greater in low HL participants than in adequate HL participants. For sensitivity (n = 162), change in SSB intake (mean difference = 7.2 fl oz) was significantly different (p ≤ 0.01) between pre-/post-IMM-BEVQ and pre-/post-dietary recalls, but not total beverage intake (mean difference = 7.6 fl oz) for all participants. Changes in SSB and total beverage intake were not significantly different for those with adequate HL. The IMM-BEVQ is a valid dietary assessment tool that is as responsive to detecting changes in beverage intake as dietary recalls. However, adults with lower HL may need additional guidance when completing the IMM-BEVQ. PMID:28025538

Incidence and time trends of childhood lymphomas: findings from 14 Southern and Eastern European cancer registries and the Surveillance, Epidemiology and End Results, USA.

PubMed

Georgakis, Marios K; Karalexi, Maria A; Agius, Domenic; Antunes, Luis; Bastos, Joana; Coza, Daniela; Demetriou, Anna; Dimitrova, Nadya; Eser, Sultan; Florea, Margareta; Ryzhov, Anton; Sekerija, Mario; Žagar, Tina; Zborovskaya, Anna; Zivkovic, Snezana; Bouka, Evdoxia; Kanavidis, Prodromos; Dana, Helen; Hatzipantelis, Emmanuel; Kourti, Maria; Moschovi, Maria; Polychronopoulou, Sophia; Stiakaki, Eftichia; Kantzanou, Μaria; Pourtsidis, Apostolos; Petridou, Eleni Th

2016-11-01

To describe epidemiologic patterns of childhood (0-14 years) lymphomas in the Southern and Eastern European (SEE) region in comparison with the Surveillance, Epidemiology and End Results (SEER), USA, and explore tentative discrepancies. Childhood lymphomas were retrieved from 14 SEE registries (n = 4,702) and SEER (n = 4,416), diagnosed during 1990-2014; incidence rates were estimated and time trends were evaluated. Overall age-adjusted incidence rate was higher in SEE (16.9/10 6 ) compared to SEER (13.6/10 6 ), because of a higher incidence of Hodgkin (HL, 7.5/10 6 vs. 5.1/10 6 ) and Burkitt lymphoma (BL, 3.1 vs. 2.3/10 6 ), whereas the incidence of non-Hodgkin lymphoma (NHL) was overall identical (5.9/10 6 vs. 5.8/10 6 ), albeit variable among SEE. Incidence increased with age, except for BL which peaked at 4 years; HL in SEE also showed an early male-specific peak at 4 years. The male preponderance was more pronounced for BL and attenuated with increasing age for HL. Increasing trends were noted in SEER for total lymphomas and NHL, and was marginal for HL, as contrasted to the decreasing HL and NHL trends generally observed in SEE registries, with the exception of increasing HL incidence in Portugal; of note, BL incidence trend followed a male-specific increasing trend in SEE. Registry-based data reveal variable patterns and time trends of childhood lymphomas in SEE and SEER during the last decades, possibly reflecting diverse levels of socioeconomic development of the populations in the respective areas; optimization of registration process may allow further exploration of molecular characteristics of disease subtypes.

Acclimation of shade-tolerant and light-resistant Tradescantia species to growth light: chlorophyll a fluorescence, electron transport, and xanthophyll content.

PubMed

Mishanin, Vladimir I; Trubitsin, Boris V; Patsaeva, Svetlana V; Ptushenko, Vasily V; Solovchenko, Alexei E; Tikhonov, Alexander N

2017-09-01

In this study, we have compared the photosynthetic characteristics of two contrasting species of Tradescantia plants, T. fluminensis (shade-tolerant species), and T. sillamontana (light-resistant species), grown under the low light (LL, 50-125 µmol photons m -2  s -1 ) or high light (HL, 875-1000 µmol photons m -2  s -1 ) conditions during their entire growth period. For monitoring the functional state of photosynthetic apparatus (PSA), we measured chlorophyll (Chl) a emission fluorescence spectra and kinetics of light-induced changes in the heights of fluorescence peaks at 685 and 740 nm (F 685 and F 740 ). We also compared the light-induced oxidation of P 700 and assayed the composition of carotenoids in Tradescantia leaves grown under the LL and HL conditions. The analyses of slow induction of Chl a fluorescence (SIF) uncovered different traits in the LL- and HL-grown plants of ecologically contrasting Tradescantia species, which may have potential ecophysiological significance with respect to their tolerance to HL stress. The fluorometry and EPR studies of induction events in chloroplasts in situ demonstrated that acclimation of both Tradescantia species to HL conditions promoted faster responses of their PSA as compared to LL-grown plants. Acclimation of both species to HL also caused marked changes in the leaf anatomy and carotenoid composition (an increase in Violaxanthin + Antheraxantin + Zeaxanthin and Lutein pools), suggesting enhanced photoprotective capacity of the carotenoids in the plants grown in nature under high irradiance. Collectively, the results of the present work suggest that the mechanisms of long-term PSA photoprotection in Tradescantia are based predominantly on the light-induced remodeling of pigment-protein complexes in chloroplasts.

Multiple vitellogenins from the Haemaphysalis longicornis tick are crucial for ovarian development.

PubMed

Boldbaatar, Damdinsuren; Umemiya-Shirafuji, Rika; Liao, Min; Tanaka, Tetsuya; Xuan, Xuenan; Fujisaki, Kozo

2010-11-01

Ovarian development and egg maturation are crucial processes for the success of reproduction in ticks. Three full-length cDNAs encoding the precursor of major yolk protein, vitellogenin, were obtained from cDNA libraries of the Haemaphysalis longicornis tick and designated as HlVg-1, HlVg-2 and HlVg-3. The HlVg mRNAs were found in fed females with major expression sites in the midgut, fat body and ovary. Native PAGE and Western blot demonstrated that HlVgs in the hemolymph, fat body and ovary of fed females consisted of four major polypeptides. RNAi results showed that HlVg dsRNA-injected ticks obtained lower body weight, egg weight and showed higher mortality of engorged females after blood sucking than control groups. Our results indicate that all HlVgs are essential for egg development and oviposition. Copyright 2010 Elsevier Ltd. All rights reserved.

Use of HL cells for improved isolation and passage of Chlamydia pneumoniae.

PubMed Central

Cles, L D; Stamm, W E

1990-01-01

We compared growth of the recently discovered respiratory pathogen Chlamydia pneumoniae in McCoy, HeLa 229, BHK-21, and HL cells. When cells were not pretreated with DEAE-dextran, HL cells had significantly higher mean numbers of inclusion-forming units (IFUs) on initial inoculation than the other cell lines. When cells were pretreated with DEAE-dextran, HeLa 229 and HL cells had equivalent mean numbers of IFUs on initial inoculation. HL cells had strikingly higher mean numbers of IFUs in passage than HeLa 229, BHK-21, or McCoy cells. In addition, HL cells did not require pretreatment with DEAE-dextran and could be used from 2 to 4 days after seeding. We conclude that HL cells are an excellent cell culture system for laboratory propagation of C. pneumoniae and may be a more sensitive cell line for initial isolation. PMID:2191013

Neurological Nuance: Hodgkin lymphoma presenting with Guillain-BarrÉ syndrome.

PubMed

Anderson, Dustin; Beecher, Grayson; Steve, Trevor A; Jen, Ho; Camicioli, Richard; Zochodne, Douglas W

2017-04-01

Hodgkin lymphoma (HL) is a common lymphoid malignancy rarely associated with Guillain-Barré syndrome (GBS). In most cases, GBS does not precede HL. We describe a patient with acute inflammatory demyelinating polyneuropathy who fulfilled criteria for GBS that heralded undiagnosed HL. Cerebrospinal fluid (CSF) studies revealed albuminocytologic dissociation with significant protein elevation (250 mg/dl). The patient worsened during intravenous immunoglobulin (IVIg) therapy. Constitutional symptoms with elevated inflammatory markers prompted further investigation, and imaging revealed an anterior mediastinal mass confirmed on biopsy to be HL. Chemotherapy yielded early clinical improvement. GBS preceding HL is rare, and this case highlights the importance of considering HL in the setting of GBS. Marked elevations in CSF protein, ongoing deterioration despite administration of IVIg, and constitutional symptoms with elevated inflammatory markers may be clues to possible HL-induced GBS. Muscle Nerve 55: 601-604, 2017. © 2016 Wiley Periodicals, Inc.

Selective killing of hepatocellular carcinoma HepG2 cells by three-dimensional nanographene nanoparticles based on triptycene

NASA Astrophysics Data System (ADS)

Xiong, Xiaoqin; Gan, Lu; Liu, Ying; Zhang, Chun; Yong, Tuying; Wang, Ziyi; Xu, Huibi; Yang, Xiangliang

2015-03-01

Carbon-based materials have been widely used in the biomedical fields including drug delivery and cancer therapies. In this paper, a recently synthesized three-dimensional nanographene (NG) based on triptycene self-assembles into nanoparticles which selectively kill human hepatocellular carcinoma HepG2 cells as compared to human normal liver HL7702 cells. Obvious differences in cellular accumulation, the endocytic pathway and intracellular trafficking of NG nanoparticles are observed in HepG2 cells and HL7702 cells. Further studies reveal that NG nanoparticles significantly increase the levels of reactive oxygen species (ROS) in HepG2 cells, but not in HL7702 cells. NG nanoparticle-induced ROS result in apoptosis induction and the decrease in mitochondrial membrane potential in HepG2 cells. Moreover, IKK/nuclear factor-κB (NF-κB) signaling is found to be activated by NG nanoparticle-induced ROS and serves to antagonize NG nanoparticle-induced apoptosis in HepG2 cells. Our studies show that the distinct behaviors of cellular uptake and ROS-mediated cytotoxicity are responsible for the selective killing of HepG2 cells. This study provides a foundation for understanding the mechanism of selective induction of apoptosis in cancer cells by NG nanoparticles and designing more effective chemotherapeutical agents.Carbon-based materials have been widely used in the biomedical fields including drug delivery and cancer therapies. In this paper, a recently synthesized three-dimensional nanographene (NG) based on triptycene self-assembles into nanoparticles which selectively kill human hepatocellular carcinoma HepG2 cells as compared to human normal liver HL7702 cells. Obvious differences in cellular accumulation, the endocytic pathway and intracellular trafficking of NG nanoparticles are observed in HepG2 cells and HL7702 cells. Further studies reveal that NG nanoparticles significantly increase the levels of reactive oxygen species (ROS) in HepG2 cells, but not in HL7702 cells. NG nanoparticle-induced ROS result in apoptosis induction and the decrease in mitochondrial membrane potential in HepG2 cells. Moreover, IKK/nuclear factor-κB (NF-κB) signaling is found to be activated by NG nanoparticle-induced ROS and serves to antagonize NG nanoparticle-induced apoptosis in HepG2 cells. Our studies show that the distinct behaviors of cellular uptake and ROS-mediated cytotoxicity are responsible for the selective killing of HepG2 cells. This study provides a foundation for understanding the mechanism of selective induction of apoptosis in cancer cells by NG nanoparticles and designing more effective chemotherapeutical agents. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07248k

Synthesis and structure-activity relationship studies of furan-ring fused chalcones as antiproliferative agents.

PubMed

Saito, Yusuke; Kishimoto, Maho; Yoshizawa, Yuko; Kawaii, Satoru

2015-02-01

As part of our continuing investigation of flavonoid derivatives as potential anticancer substances, the synthesis of 25 cinnamoyl derivatives of benzofuran as furan-fused chalcones was carried-out and these compounds were further evaluated for their antiproliferative activity towards HL60 promyelocytic leukemia cells. In comparison with 2',4'-dihydroxychalcone, attachment of a furan moiety on the A-ring enhanced activity by more than twofold. Benzofurans may be useful in the design of biologically active flavonoids. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

HMG CoA lyase deficiency: identification of five causal point mutations in codons 41 and 42, including a frequent Saudi Arabian mutation, R41Q.

PubMed Central

Mitchell, G A; Ozand, P T; Robert, M F; Ashmarina, L; Roberts, J; Gibson, K M; Wanders, R J; Wang, S; Chevalier, I; Plöchl, E; Miziorko, H

1998-01-01

The hereditary deficiency of 3-hydroxy-3-methylglutaryl (HMG) CoA lyase (HL; OMIM 246450 [http://www3.ncbi.nlm.nih. gov:80/htbin-post/Omim/dispmim?246450]) results in episodes of hypoketotic hypoglycemia and coma and is reported to be frequent and clinically severe in Saudi Arabia. We found genetic diversity among nine Saudi HL-deficient probands: six were homozygous for the missense mutation R41Q, and two were homozygous for the frameshift mutation F305fs(-2). In 32 non-Saudi HL-deficient probands, we found three R41Q alleles and also discovered four other deleterious point mutations in codons 41 and 42: R41X, D42E, D42G, and D42H. In purified mutant recombinant HL, all four missense mutations in codons 41 and 42 cause a marked decrease in HL activity. We developed a screening procedure for HL missense mutations that yields residual activity at levels comparable to those obtained using purified HL peptides. Codons 41 and 42 are important for normal HL catalysis and account for a disproportionate 21 (26%) of 82 of mutant alleles in our group of HL-deficient probands. PMID:9463337

Genetic basis of hearing loss in Spanish, Hispanic and Latino populations.

PubMed

Mittal, Rahul; Patel, Amit P; Nguyen, Desiree; Pan, Debbie R; Jhaveri, Vasanti M; Rudman, Jason R; Dharmaraja, Arjuna; Yan, Denise; Feng, Yong; Chapagain, Prem; Lee, David J; Blanton, Susan H; Liu, Xue Zhong

2018-03-20

Hearing loss (HL) is the most common neurosensory disorder affecting humans. The screening, prevention and treatment of HL require a better understanding of the underlying molecular mechanisms. Genetic predisposition is one of the most common factors that leads to HL. Most HL studies include few Spanish, Hispanic and Latino participants, leaving a critical gap in our understanding about the prevalence, impact, unmet health care needs, and genetic factors associated with hearing impairment among Spanish, Hispanic and Latino populations. The few studies which have been performed show that the gene variants commonly associated with HL in non-Spanish and non-Hispanic populations are infrequently responsible for hearing impairment in Spanish as well as Hispanic and Latino populations (hereafter referred to as Hispanic). To design effective screening tools to detect HL in Spanish and Hispanic populations, studies must be conducted to determine the gene variants that are most commonly associated with hearing impairment in this racial/ethnic group. In this review article, we summarize gene variants and loci associated with HL in Spanish and Hispanic populations. Identifying new genetic variants associated with HL in Spanish and Hispanic populations will pave the way to develop effective screening tools and therapeutic strategies for HL. Copyright © 2018 Elsevier B.V. All rights reserved.

Auditory, visual, and auditory-visual perceptions of emotions by young children with hearing loss versus children with normal hearing.

PubMed

Most, Tova; Michaelis, Hilit

2012-08-01

This study aimed to investigate the effect of hearing loss (HL) on emotion-perception ability among young children with and without HL. A total of 26 children 4.0-6.6 years of age with prelingual sensory-neural HL ranging from moderate to profound and 14 children with normal hearing (NH) participated. They were asked to identify happiness, anger, sadness, and fear expressed by an actress when uttering the same neutral nonsense sentence. Their auditory, visual, and auditory-visual perceptions of the emotional content were assessed. The accuracy of emotion perception among children with HL was lower than that of the NH children in all 3 conditions: auditory, visual, and auditory-visual. Perception through the combined auditory-visual mode significantly surpassed the auditory or visual modes alone in both groups, indicating that children with HL utilized the auditory information for emotion perception. No significant differences in perception emerged according to degree of HL. In addition, children with profound HL and cochlear implants did not perform differently from children with less severe HL who used hearing aids. The relatively high accuracy of emotion perception by children with HL may be explained by their intensive rehabilitation, which emphasizes suprasegmental and paralinguistic aspects of verbal communication.

The inhibitory activity of HL-7 and HL-10 peptide from scorpion venom (Hemiscorpius lepturus) on angiotensin converting enzyme: Kinetic and docking study.

PubMed

Setayesh-Mehr, Zahra; Asoodeh, Ahmad

2017-12-01

The hypertension is one of the highest risk factors for stroke, myocardial infarction, vascular disease and chronic kidney disease. Angiotensin converting enzyme (ACE) has an important role in the physiological regulation of cardiovascular system. ACE inhibition is a key purpose for hypertension treatment. In this study, two peptides named HL-7 with the sequence of YLYELAR (MW: 927.07Da) and HL-10 with the sequence of AFPYYGHHLG (MW: 1161.28Da) were identified from scorpion venom of H. lepturus. The inhibitory activity of HL-7 and HL-10 was examined on rabbit ACE. The inhibition mechanisms were assayed by kinetic and docking studies. The IC 50 values for ACE inhibition of HL-7 and HL-10 were 9.37µM and 17.22µM, respectively. Lineweaver-Burk plots showed that two peptides inhibited rabbit ACE with competitive manner. The molecular docking conformed experimental results and showed that the two peptides interacted with N-domain and C-domain active sites. Also, docking study revealed that the two peptides can form hydrogen and hydrophobic bonds at their binding sites. Both peptides had higher affinity to N-domain. Our results showed that HL-7 exhibited more strong interactions with amino acids at active site. It seems that HL-10 peptide could occupy more space, thereby inhibiting the substrate entrance to active site. Copyright © 2017 Elsevier Inc. All rights reserved.

[Effect of Magnolol on Proliferation and Apoptosis of HL-60 Cells and Its Molecular Mechanism].

PubMed

Fang, Ke; Yuan, Xiao-Fen; Liao, Qiong; Zhang, Zhi-Yong; Song, Guan-Hua; Guo, Qiang; Ren, Xia; Jiang, Guo-Sheng

2016-04-01

To investigate the effect of magnolol on proliferation and apoptosis of HL-60 cells and its mechanism. MTT assay was used to measure the proliferation of HL-60 cells after treatment with different concentration of magnolol (5, 10, 20, 40, 80 and 160 µg/ml). The morphological changes of HL-60 cells were examined by light microscopy, and DAPI staining was performed to observe the nuclear morphology of HL-60 cells. The early cell apoptosis was detected by flow cytometry with Annexin V-FITC/PI double-staining. RT-PCR was carried out to examine the mRNA expression of BAX and BCL-2. Western blot was performed to detect the protein expression of caspase family. The magnolol inhibited HL-60 cell proliferation, and the inhibitory rate of cell proliferation increased significantly in a dose- and time- dependent manner (P < 0.05). HL-60 cells became small, even apoptotic bodies appeared after treatment with magnolol. In addition, nuclear condensation or fragmentation could be observed, which is the typical morphological features of apoptosis. When HL-60 cells were treated with 40 µg/ml of magnolol for 24 h, the ratio of early apoptotic cells reached to (11.7 ± 2.4) %, which was significant different from control (1.4 ± 1.1) % (P < 0.05). RT-PCR results showed that treatment of HL-60 cells with magnolol up-regulated the expression of BAX, whereas down-regulated the expression of BCL-2. Western blot results showed that the cleavages of caspase-3, -8 and -9 were significantly enhanced by magnolol. The magnolol can significantly inhibit the proliferation of HL-60 cells and induce the apoptosis of HL-60 cells, which may occur through up-regulation of BAX, down-regulation of BCL-2 and the activation of caspases.

Risk of Second Cancer in Hodgkin Lymphoma Survivors and Influence of Family History.

PubMed

Sud, Amit; Thomsen, Hauke; Sundquist, Kristina; Houlston, Richard S; Hemminki, Kari

2017-05-10

Purpose Although advances in Hodgkin lymphoma (HL) treatment have led to improved disease-free survival, this has been accompanied by an increased risk of second cancers. We sought to quantify the second cancer risks and to investigate the impact of family history. Patients and Methods Using the Swedish Family-Cancer Project Database, we identified 9,522 individuals with primary HL diagnosed between 1965 and 2012. We calculated standardized incidence ratios and cumulative incidence of second cancer in HL survivors and compared the standardized incidence ratios of lung, breast, colorectal, and all second cancers in HL survivors with and without a site-specific family history of cancer. Interactions between family history of cancer and HL treatment were evaluated under additive and multiplicative models. Results Overall, the risk of a second cancer in HL survivors was increased 2.39-fold (95% CI, 2.29 to 2.53). The 30-year cumulative incidence of breast cancer in women diagnosed with HL at younger than 35 years of age was 13.8%. We observed no significant difference in cancer risk over successive time periods. The risk of all second cancers was 1.3-fold higher for HL survivors with a first-degree relative with cancer ( P < .001), with 3.3-fold, 2.1-fold, and 1.8-fold differences shown for lung, colorectal, and breast cancers, respectively. Moreover, a greater than additive interaction between family history of lung cancer and HL treatment was shown ( P = .03). Conclusion HL survivorship is associated with a substantive risk of a second cancer. Notably, the risk is higher in individuals with a family history of cancer. This information should be used to inform risk-adapted therapy and to assist in screening to reduce long-term morbidity and mortality in patients with HL.

Risk of Second Cancer in Hodgkin Lymphoma Survivors and Influence of Family History

PubMed Central

Sud, Amit; Thomsen, Hauke; Sundquist, Kristina; Houlston, Richard S.; Hemminki, Kari

2017-01-01

Purpose Although advances in Hodgkin lymphoma (HL) treatment have led to improved disease-free survival, this has been accompanied by an increased risk of second cancers. We sought to quantify the second cancer risks and to investigate the impact of family history. Patients and Methods Using the Swedish Family-Cancer Project Database, we identified 9,522 individuals with primary HL diagnosed between 1965 and 2012. We calculated standardized incidence ratios and cumulative incidence of second cancer in HL survivors and compared the standardized incidence ratios of lung, breast, colorectal, and all second cancers in HL survivors with and without a site-specific family history of cancer. Interactions between family history of cancer and HL treatment were evaluated under additive and multiplicative models. Results Overall, the risk of a second cancer in HL survivors was increased 2.39-fold (95% CI, 2.29 to 2.53). The 30-year cumulative incidence of breast cancer in women diagnosed with HL at younger than 35 years of age was 13.8%. We observed no significant difference in cancer risk over successive time periods. The risk of all second cancers was 1.3-fold higher for HL survivors with a first-degree relative with cancer (P < .001), with 3.3-fold, 2.1-fold, and 1.8-fold differences shown for lung, colorectal, and breast cancers, respectively. Moreover, a greater than additive interaction between family history of lung cancer and HL treatment was shown (P = .03). Conclusion HL survivorship is associated with a substantive risk of a second cancer. Notably, the risk is higher in individuals with a family history of cancer. This information should be used to inform risk-adapted therapy and to assist in screening to reduce long-term morbidity and mortality in patients with HL. PMID:28384078

Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin's Lymphoma Prior to Any Treatment Are Predictive of Second Cancers

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

M'kacher, Radhia; Bennaceur-Griscelli, Annelise; Girinsky, Theodore

Purpose: To investigate a potential link between telomere length, chromosomal instability, and the advent of a second cancer (SC) in patients with Hodgkin's lymphoma (HL), who are known to be at risk for SCs. This study was premised on the finding that telomere dysfunction and DNA repair pathways were related to many pathologic conditions. Methods and Materials: Three cohorts of patients with HL were studied: 73 who were prospectively followed >5 years after diagnosis (prospective HL cohort), 28 who developed a SC (SC HL cohort), and 18 long-term survivors with no evidence of disease or complication since their initial treatmentmore » (NED HL cohort). Telomere length was analyzed by a telomeric restriction fragment assay in peripheral blood lymphocytes. Thirty healthy donors and 70 patients with a newly diagnosed solid tumor were the control population. Results: Compared with controls, patients from the prospective HL cohort, before any treatment, showed age-independent shorter telomeres (mean, 8.3 vs. 11.7 kb in healthy donors; <6 kb in 18% in HL patients), increased spontaneous chromosomal abnormalities, and increased in vitro radiation sensitivity (p < 10{sup -4} each). After treatment, telomere shortening was associated with cytogenetic profiles characterized by the persistence of complex chromosomal rearrangement and clonal aberrations. Moreover, the two cases of SC in the prospective HL patients had short telomeres and CCR initially. In addition, the SC HL cohort was characterized by markedly short telomeres (6.6 vs. 9.7 kb in the NED HL cohort), the presence of complex chromosome rearrangements, and increased in vitro radiation sensitivity. Conclusions: An intimate relationship between pre-treatment telomere shortening, chromosomal instability, radiation sensitivity and occurrence of SC was found in HL patients.« less

HL-10 cockpit

NASA Technical Reports Server (NTRS)

1967-01-01

Cockpit of the HL-10 lifting body. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials.

PubMed

Bröckelmann, Paul J; Goergen, Helen; Kohnhorst, Charlotte; von Tresckow, Bastian; Moccia, Alden; Markova, Jana; Meissner, Julia; Kerkhoff, Andrea; Ludwig, Wolf-Dieter; Fuchs, Michael; Borchmann, Peter; Engert, Andreas

2017-05-01

Purpose Clinical characteristics, therapeutic approaches, and prognosis of late relapse (LR) in patients with classic Hodgkin lymphoma (cHL) are poorly understood. We performed a comprehensive analysis of LR of Hodgkin lymphoma (LR-HL). Methods To estimate the incidence of LR-HL, we retrospectively analyzed 6,840 patients with cHL included in the German Hodgkin Study Group trials HD7 to HD12. Patients who experienced a relapse > 5 years into remission were compared with patients in continued remission for > 5 years and with those who experienced a relapse ≤ 5 years after first diagnosis. Results With a median observation time of 10.3 years, 141 incidences of LR-HL were observed. Cumulative incidences at 10, 15, and 20 years rose linearly and were 2.5%, 4.3%, and 6.9%, respectively. The standardized incidence ratio for HL with respect to age- and sex-matched German reference data was 84.5 (95% CI, 71.2 to 99.7). LR-HL was more frequently observed in patients with early-stage favorable than unfavorable or advanced stage at first diagnosis (15-year cumulative incidence, 5.3% v 3.9% and 3.9%, respectively; P = .01). Overall survival from first diagnosis was worse after LR compared with nonrelapse survivors (10-year estimate, 95.8% v 86.1%; hazard ratio, 2.5; 95% CI, 1.7 to 3.5; P < .001). In patients with LR-HL, survival was better compared with 466 patients with earlier relapse (hazard ratio, 0.6; 95% CI, 0.4 to 0.9, P = .01). Forty-four percent and 49% of patients with LR-HL and earlier relapse, respectively, received stem cell transplantations. Conclusion Apart from treatment-associated adverse effects, survivors after initially successful therapy for cHL are at an 85-fold risk for recurrence of disease compared with the general German population. After risk-adapted treatment strategies, especially in early-stage favorable HL, regular clinical follow-up is recommended for timely detection of LR-HL. With adequate treatment, prognosis of LR-HL is better compared with early relapses.

HL-10 in flight, turning to line up with lakebed runway 18

NASA Technical Reports Server (NTRS)

1969-01-01

This photo shows the HL-10 in flight, turning to line up with lakebed runway 18. The pilot for this flight, the 29th of the HL-10 series, was Bill Dana. The HL-10 reached a peak altitude of 64,590 feet and a top speed of Mach 1.59 on this particular flight. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Pilot Peter Hoag and HL-10

NASA Technical Reports Server (NTRS)

1969-01-01

Air Force Major Peter Hoag stands in front of the HL-10 Lifting Body. Maj. Hoag joined the HL-10 program in 1969 and made his first glide flight on June 6, 1969. He made a total of 8 flights in the HL-10. They included the fastest lifting-body flight, which reached Mach 1.861 on Feb. 18, 1970. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Health literacy, source of information and impact on adherence to therapy in people living with HIV

PubMed Central

Ernst Dorner, Thomas; Schulte-Hermann, Kathrin; Zanini, Matteo; Leichsenring, Birgit; Stefanek, Wiltrut

2014-01-01

Introduction Adequate information and health literacy (HL) has a high impact on patients understanding on the causes and consequences of many chronic diseases, including HIV, and is a crucial prerequisite to ensure adherence to therapy regimens. Several Austrian patient organizations developed an online survey together with MSD (the so-called “PAB-test”) aimed to evaluate how people living with HIV perceive the level of care in Austria. Materials and Methods An online survey has been developed to assess HL in people living with HIV and to evaluate the impact of HL on therapy adherence. HL was assessed with seven items regarding the self-rated comprehension of HIV related information, which showed a high reliability (Cronbach's alpha=0.876). A low health literacy was defined by reaching a score below the median of 20 points in the related indicator. Results A total of 303 subjects completed the questionnaire. Women slightly had more often a low HL than men (57.1% vs 44.7%, p=0.335). Heterosexual subjects had more often a low HL compared to homosexual ones (58.3% vs 38.1%, p=0.007). Health literacy slightly increased with age (not significant). An increasing education level correlated with higher HL, (66.7%, 46.2%, and 38.9% of persons showed low HL with primary, secondary and tertiary education, respectively, p=0.037). The number of missed appointments with the HIV physician was significantly higher in the low HL population (30.0% vs 14.4%, p=0.002), which also showed to be more prone to interrupt the therapy without consulting a physician (22.4% vs 9.8%, p=0.006). The low HL population, however, did not report of having forgotten the medication intake more often than the one with high HL (33.1% vs 39.1%, p=0.305). The most important source of information is the treating physician, followed by NGOs/patient organizations and the internet (Figure 1). Conclusions There are significant differences in HL between different sub-groups in the HIV community. Low HL is significantly associated with a higher frequency of missed doctor appointments and interruptions of treatment, but does not impact adherence to therapy (self-reported). The identified information providers (medical doctors, NGOs/patient organizations) should be encouraged to contribute towards increased HL in HIV patients. PMID:25394103

Environmental Assessment: Proposed Consolidated Warehouse, Hill Air Force Base, Utah

DTIC Science & Technology

2011-02-01

can be evaluated. It...420 916 180 243 50 3 37 206 50 7 G 43 91 5 508 57 0 47 0 847 896 341 50 5 5 39 50 9 24 0 58 1 5 16 42 849 13 77 883 C 295 840 430 125 U -01-HL- 0164m U ...91-WC-687m U -95-WC-28OP U -02-HL-0008m Proposed Action (Alternative A) Future Training Complex Alternate Location (Alternative D) Fu tu re Au to m

Spectral, biological screening of metal chelates of chalcone based Schiff bases of N-(3-aminopropyl) imidazole.

PubMed

Kalanithi, M; Rajarajan, M; Tharmaraj, P; Sheela, C D

2012-02-15

Tridentate chelate complexes of Co(II), Ni(II), Cu(II) and Zn(II) have been synthesized from the chalcone based ligands 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-(phenylallyl)]phenol(HL(1)), 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-p-tolylallyl]phenol(HL(2)), 2-[1-(3-(1H-imidazol-1-yl)propylimino)-3-4-nitrophenylallyl]phenol(HL(3)). Microanalytical data, UV-vis spectrophotometric method, magnetic susceptibility measurements, IR, 1H NMR, Mass, and EPR techniques were used to characterize the structure of chelates. The electronic absorption spectra and magnetic susceptibility measurements suggest a distorted square planar geometry for the copper(II) ion. The other metal complexes show distorted tetrahedral geometry. The coordination of the ligands with metal(II) ions was further confirmed by solution fluorescence spectrum. The antimicrobial activity of the ligands and metal(II) complexes against the species Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albigans and Aspergillus niger has been carried out and compared. The electrochemical behavior of copper(II) complex is studied by cyclic voltammetry. Copyright © 2011 Elsevier B.V. All rights reserved.

Synthesis, characterization, crystal structure, DNA- and HSA-binding studies of a dinuclear Schiff base Zn(II) complex derived from 2-hydroxynaphtaldehyde and 2-picolylamine

NASA Astrophysics Data System (ADS)

Kazemi, Zahra; Rudbari, Hadi Amiri; Mirkhani, Valiollah; Sahihi, Mehdi; Moghadam, Majid; Tangestaninejad, Sharam; Mohammadpoor-Baltork, Iraj

2015-09-01

A tridentate Schiff base ligand NNO donor (HL: 1-((E)-((pyridin-2-yl)methylimino)methyl)naphthalen-2-ol was synthesized from condensation of 2-hydroxynaphtaldehyde and 2-picolylamine. Zinc complex, Zn2L2(NO3)2, was prepared from reaction of Zn(NO3)2 and HL at ambient temperature. The ligand and complex were characterized by FT-IR, 1H NMR, 13C NMR and elemental analysis (CHN). Furthermore, the structure of dinuclear Zn(II) complex was determined by single crystal X-ray analysis. The complex, Zn2L2(NO3)2, is centrosymmetric dimer in which deprotonated phenolates bridge the two Zn(II) atoms and link the two halves of the dimer. In the structure, Zinc(II) ions have a highly distorted six-coordinate structure bonded to two oxygen atoms from a bidentate nitrate group, the pyridine nitrogen, an amine nitrogen and phenolate oxygens. The interaction of dinuclear Zn(II) complex with fish sperm DNA (FS-DNA) and HSA was investigated under physiological conditions using fluorescence quenching, UV-Vis spectroscopy, molecular dynamics simulation and molecular docking methods. The estimated binding constants for the DNA-complex and HSA-complex were (3.60 ± 0.18) × 104 M-1 and (1.35 ± 0.24) × 104 M-1, respectively. The distance between dinuclear Zn(II) complex and HSA was obtained based on the Förster's theory of non-radiative energy transfer. Molecular docking studies revealed the binding of dinuclear Zn(II) complex to the major groove of FS-DNA and IIA site of protein by formation of hydrogen bond, π-cation and hydrophobic interactions.

Undifferentiated HL-60 cells internalize an antitumor alkyl ether phospholipid more rapidly than resistant K562 cells.

PubMed

Tsutsumi, T; Tokumura, A; Kitazawa, S

1998-02-05

In this study, we confirmed a previous finding that 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (methyl-PAF) expresses higher antineoplastic activity against the promyelocytic leukemia cell line HL-60, than against the erythroleukemic cell line K562, and intended to clarify the reason for this. Using an albumin back-exchange method, we measured the rates of binding and internalization of [3H]methyl-PAF by HL-60 and K562 cells. We found that methyl-PAF associated very rapidly and to similar extents with the two types of cells at low concentrations of extracellular bovine serum albumin, but that when bound to the cell surface, it was internalized into HL-60 cells faster than into K562 cells. The internalization of methyl-PAF by HL-60 cells was concentration-independent, intracellular ATP-independent and susceptible to thiol group-modifying reagents and cytochalasin B. Thus the inward transbilayer movement of methyl-PAF seems to occur by cytochalasin B-sensitive protein-mediated mechanism based on passive diffusion not requiring energy, in which SH-groups of protein play a critical role. We also found that the internalization of 1-hexadecanoyl-2-(4,4-difluoro-5,7- dimethyl-4-bora-3a, 4a-diaza-s-indacene-3-pentanoyl)-sn-glycero-3-phosphocholine (Bodipy-C5-PC), whose structure resembles that of methyl-PAF, into HL-60 cells was faster than that into K562 cells. Using a combination of an albumin back-exchange method and observation by confocal laser scanning microscopy, we next examined the intracellular distribution of this fluorescent phospholipid probe after its internalization. Intracellular membranes, especially those peripheral to nuclei, were fluorescence-labeled in both HL-60 and K562 cells, but fluorescence of the nuclear membranes was weak, suggesting that this probe seems mainly to accumulate in intracellular granules, and may interact directly with several key enzymes for phospholipid metabolism, leading to cell injury. Because the difference between the internalization rates of methyl-PAF in HL-60 and K562 cells was correlated with their different susceptibilities to the cytotoxic effect of methyl-PAF, we suggest that the capacities for uptake of methyl-PAF and its accumulation in intracellular membranes are critical factor for its induction of apoptosis. (c) 1998 Elsevier Science B.V.

Metal based biologically active compounds: Design, synthesis, DNA binding and antidiabetic activity of 6-methyl-3-formyl chromone derived hydrazones and their metal (II) complexes.

PubMed

Philip, Jessica Elizabeth; Shahid, Muhammad; Prathapachandra Kurup, M R; Velayudhan, Mohanan Puzhavoorparambil

2017-10-01

Two chromone hydrazone ligands HL 1 and HL 2 were synthesized and characterized by elemental analyses, IR, 1 H NMR & 13 C NMR, electronic absorption and mass spectra. The reactions of the chromone hydrazones with transition metals such as Ni, Cu, and Zn (II) salts of acetate afforded mononuclear metal complexes. Characterization and structure elucidation of the prepared chromone hydrazone metal (II) complexes were done by elemental, IR, electronic, EPR spectra and thermo gravimetric analyses as well as conductivity and magnetic susceptibility measurements. The spectroscopic data showed that the ligand acts as a mono basic bidentate with coordination sites are azomethine nitrogen and hydrazonic oxygen, and they exhibited distorted geometry. The biological studies involved antidiabetic activity i.e. enzyme inhibition of α-amylase and α-glucosidase, Calf Thymus - DNA (CT-DNA) interaction and molecular docking. Potential capacity of synthesized compounds to inhibit the α-amylase and α-glucosidase activity was assayed whereas DNA interaction studies were carried out with the help UV-Vis absorption titration and viscosity method. The docking studies of chromone hydrazones show that they are minor groove binders. Complexes were found to be good DNA - intercalates. Chromone hydrazones and its transition metal complexes have shown comparable antidiabetic activity with a standard drug acarbose. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanoleakage in Hybrid Layer and Acid-Base Resistant Zone at the Adhesive/Dentin Interface.

PubMed

Nikaido, Toru; Nurrohman, Hamid; Takagaki, Tomohiro; Sadr, Alireza; Ichinose, Shizuko; Tagami, Junji

2015-10-01

The aim of interfacial nanoleakage evaluation is to gain a better understanding of degradation of the adhesive-dentin interface. The acid-base resistant zone (ABRZ) is recognized at the bonded interface under the hybrid layer (HL) in self-etch adhesive systems after an acid-base challenge. The purpose of this study was to evaluate nanoleakage in HL and ABRZ using three self-etch adhesives; Clearfil SE Bond (SEB), Clearfil SE One (SEO), and G-Bond Plus (GBP). One of the three adhesives was applied on the ground dentin surface and light cured. The specimens were longitudinally divided into two halves. One half remained as the control group. The others were immersed in ammoniacal silver nitrate solution, followed by photo developing solution under fluorescent light. Following this, the specimens were subjected to acid-base challenges with an artificial demineralization solution (pH4.5) and sodium hypochlorite, and prepared in accordance with common procedures for transmission electron microscopy (TEM) examination. The TEM images revealed silver depositions in HL and ABRZ due to nanoleakage in all the adhesives; however, the extent of nanoleakage was material dependent. Funnel-shaped erosion beneath the ABRZ was observed only in the all-in-one adhesive systems; SEO and GBP, but not in the two-step self-etch adhesive system; SEB.

Bardoxolone Methyl and a Related Triterpenoid Downregulate cMyc Expression in Leukemia Cells

PubMed Central

Jin, Un-Ho; Cheng, Yating; Zhou, Beiyan

2017-01-01

Structurally related pentacyclic triterpenoids methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate [bardoxolone-methyl (Bar-Me)] and methyl 2-trifluoromethyl-3,11-dioxoolean-1,12-dien-30-oate (CF3DODA-Me) contain 2-cyano-1-en-3-one and 2-trifluoromethyl-1-en-3-one moieties, respectively, in their A-rings and differ in the position of their en-one structures in ring C. Only Bar-Me forms a Michael addition adduct with glutathione (GSH) and inhibits IKKβ phosphorylation. These differences may be due to steric hindrance by the 11-keto group in CF3DODA-Me, which prevents Michael addition by the conjugated en-one in the A-ring. In contrast, both Bar-Me and CF3DODA-Me induce reactive oxygen species in HL-60 and Jurkat leukemia cells, inhibit cell growth, induce apoptosis and differentiation, and decrease expression of specificity proteins (Sp) 1, 3, and 4, and cMyc, and these effects are significantly attenuated after cotreatment with the antioxidant GSH. In contrast to solid tumor–derived cells, cMyc and Sp transcriptions are regulated independently and cMyc plays a more predominant role than Sp transcription factors in regulating HL-60 or Jurkat cell proliferation and differentiation compared with that observed in cells derived from solid tumors. PMID:28275049

Structural, spectral and magnetic studies of two Co(II)-N-heterocyclic diphosphonates based on multinuclear units

NASA Astrophysics Data System (ADS)

Zhao, Chen; Ma, Kui-Rong; Zhang, Yu; Kan, Yu-He; Li, Rong-Qing; Hu, Hua-You

2016-01-01

Two examples of Co(II)-N-heterocyclic coordination polymers based on 1-hydroxyethylidenediphosphonic acid (H5L = CH3C(OH)(PO3H2)2), namely 0.5(H3NCH2CH2NH3)·[Co6(Cl2)(H3L)2(H2L)(HL)(2,2‧-bipy)6] 1 and 2(NH4)·[Co3(HL)2(H2O)2(phen)2]·2(H2O) 2, have been solvothermally obtained by introducing the second ligands 2,2‧-bipyridine/1,10-phenanthroline (2,2‧-bipy/phen) and characterized by powder X-ray diffraction (PXRD), elemental analysis, IR, TG-DSC. The single-crystal X-ray diffractions show that compound 1 possesses a 0-D structure with hexa-nuclear cluster [Co6(O-P-O)8] built through single/double O-P-O bridges and compound 2 displays a 1-D ladder-like chain structure with magnetic topology building blocks [Co4(O-P-O)4]n. Then H-bonding and π-π stacking interactions further expand the two low-dimensional structures into three-dimensional supramolecular frameworks. Fluorescent measurements reveal that both the maximum emission peaks of 1-2 are centered at 423 nm, mainly deriving from intraligand π*-π transition state of N-heterocyclic ligand 2,2‧-bipy/phen, respectively. Magnetism data indicate that 1 exhibits antiferromagnetic behavior within hexa-nuclear Co(II) clusters, while 2 shows weak ferromagnetic interactions in 1-D topology Co(II)-chain, showing promising potential as magnetic materials.

Convergence of Health Level Seven Version 2 Messages to Semantic Web Technologies for Software-Intensive Systems in Telemedicine Trauma Care

PubMed Central

Cook, Timothy Wayne; Cavalini, Luciana Tricai

2016-01-01

Objectives To present the technical background and the development of a procedure that enriches the semantics of Health Level Seven version 2 (HL7v2) messages for software-intensive systems in telemedicine trauma care. Methods This study followed a multilevel model-driven approach for the development of semantically interoperable health information systems. The Pre-Hospital Trauma Life Support (PHTLS) ABCDE protocol was adopted as the use case. A prototype application embedded the semantics into an HL7v2 message as an eXtensible Markup Language (XML) file, which was validated against an XML schema that defines constraints on a common reference model. This message was exchanged with a second prototype application, developed on the Mirth middleware, which was also used to parse and validate both the original and the hybrid messages. Results Both versions of the data instance (one pure XML, one embedded in the HL7v2 message) were equally validated and the RDF-based semantics recovered by the receiving side of the prototype from the shared XML schema. Conclusions This study demonstrated the semantic enrichment of HL7v2 messages for intensive-software telemedicine systems for trauma care, by validating components of extracts generated in various computing environments. The adoption of the method proposed in this study ensures the compliance of the HL7v2 standard in Semantic Web technologies. PMID:26893947

The Effect of TNF-α Blocker HL036337 and Its Best Concentration to Inhibit Dry Eye Inflammation.

PubMed

Choi, Wungrak; Noh, Hyemi; Yeo, Areum; Jang, Hanmil; Ahn, Hyea Kyung; Song, Yeon Jung; Lee, Hyung Keun

2016-08-01

Dry eye syndrome is commonly thought of as an inflammatory disease, and we have previously presented data showing the effectiveness of topical TNF-α blocker agents for the treatment of this condition. The purpose of this study was to investigate the effectiveness of the TNF-α blocking agent HL036337 compared to cyclosporine A for the treatment of dry eye induced inflammation in order to establish whether HL036337 represents a more effective method for suppressing inflammation. The efficacy of HL036337 and cyclosporine A was determined using an experimental murine dry eye model. The TNF-α blocker HL036337 is a modified form of TNF receptor I. Using dry eye induced C57BL/6 mice (n = 45), corneal erosion was measured at day 4 and 7 after topical treatment with cyclosporine A or HL036337. To determine the effective treatment dose, 0.25, 0.5, 1, 2.5, and 5 mg/mL of HL036337 were topically administered twice per day to dry eye induced murine corneas for 1 week. The optimal concentration of the TNF-α blocker HL036337 for treatment of dry eye induced corneal erosion was determined to be 1 mg/mL. Dry eye induced corneal erosion was improved after 1 week with topically applied cyclosporine A and HL036337 at 1 mg/mL. HL036337 administered topically at 1 mg/mL effectively improved corneal erosion induced by dry eye. This finding may also suggest that inhibition of TNF-α can improve dry eye syndrome.

Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake.

PubMed

Cedó, Lídia; Santos, David; Roglans, Núria; Julve, Josep; Pallarès, Victor; Rivas-Urbina, Andrea; Llorente-Cortes, Vicenta; Laguna, Joan Carles; Blanco-Vaca, Francisco; Escolà-Gil, Joan Carles

2017-01-01

Human hepatic lipase (hHL) is mainly localized on the hepatocyte cell surface where it hydrolyzes lipids from remnant lipoproteins and high density lipoproteins and promotes their hepatic selective uptake. Furthermore, hepatic lipase (HL) is closely associated with obesity in multiple studies. Therefore, HL may play a key role on lipid homeostasis in liver and white adipose tissue (WAT). In the present study, we aimed to evaluate the effects of hHL expression on hepatic and white adipose triglyceride metabolism in vivo. Experiments were carried out in hHL transgenic and wild-type mice fed a Western-type diet. Triglyceride metabolism studies included β-oxidation and de novo lipogenesis in liver and WAT, hepatic triglyceride secretion, and adipose lipoprotein lipase (LPL)-mediated free fatty acid (FFA) lipolysis and influx. The expression of hHL promoted hepatic triglyceride accumulation and de novo lipogenesis without affecting triglyceride secretion, and this was associated with an upregulation of Srebf1 as well as the main genes controlling the synthesis of fatty acids. Transgenic mice also exhibited more adiposity and an increased LPL-mediated FFA influx into the WAT without affecting glucose tolerance. Our results demonstrate that hHL promoted hepatic steatosis in mice mainly by upregulating de novo lipogenesis. HL also upregulated WAT LPL and promoted triglyceride-rich lipoprotein hydrolysis and adipose FFA uptake. These data support the important role of hHL in regulating hepatic lipid homeostasis and confirm the broad cardiometabolic role of HL.

Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake

PubMed Central

Cedó, Lídia; Santos, David; Roglans, Núria; Julve, Josep; Pallarès, Victor; Rivas-Urbina, Andrea; Llorente-Cortes, Vicenta; Laguna, Joan Carles

2017-01-01

Human hepatic lipase (hHL) is mainly localized on the hepatocyte cell surface where it hydrolyzes lipids from remnant lipoproteins and high density lipoproteins and promotes their hepatic selective uptake. Furthermore, hepatic lipase (HL) is closely associated with obesity in multiple studies. Therefore, HL may play a key role on lipid homeostasis in liver and white adipose tissue (WAT). In the present study, we aimed to evaluate the effects of hHL expression on hepatic and white adipose triglyceride metabolism in vivo. Experiments were carried out in hHL transgenic and wild-type mice fed a Western-type diet. Triglyceride metabolism studies included β-oxidation and de novo lipogenesis in liver and WAT, hepatic triglyceride secretion, and adipose lipoprotein lipase (LPL)-mediated free fatty acid (FFA) lipolysis and influx. The expression of hHL promoted hepatic triglyceride accumulation and de novo lipogenesis without affecting triglyceride secretion, and this was associated with an upregulation of Srebf1 as well as the main genes controlling the synthesis of fatty acids. Transgenic mice also exhibited more adiposity and an increased LPL-mediated FFA influx into the WAT without affecting glucose tolerance. Our results demonstrate that hHL promoted hepatic steatosis in mice mainly by upregulating de novo lipogenesis. HL also upregulated WAT LPL and promoted triglyceride-rich lipoprotein hydrolysis and adipose FFA uptake. These data support the important role of hHL in regulating hepatic lipid homeostasis and confirm the broad cardiometabolic role of HL. PMID:29244870

An assessment of streamflow vulnerability to climate using ...

EPA Pesticide Factsheets

Identifying regions with similar hydrology is useful for assessing water quality and quantity across the U.S., especially areas that are difficult or costly to monitor. For example, hydrologic landscapes (HLs) have been used to map streamflow variability and assess the spatial distribution of climatic response in Oregon, Alaska, and the Pacific Northwest. HLs have also been applied to assess historic and projected climatic impacts across the Western U.S. In this project, we summarized (1) the HL classification methodology and (2) the utility of using HLs as a tool to classify the vulnerability of streams to climatic changes in the Western U.S. During the HL classification process, we analyzed climate, seasonality, aquifer permeability, terrain, and soil permeability as the primary hydrologic drivers (and precipitation intensity as a secondary driver) associated with large scale hydrologic processes (storage, conveyance, and flow of water into or out of the watershed) in the West. We derived the dominant hydrologic pathways (surface runoff or deep or shallow groundwater) from the HL classification of different catchments to test our hypotheses: 1) Changes in climate will have greater impacts on streamflow in catchments dominated by surface runoff. 2) Catchments historically fed by surface runoff from winter snowmelt in the spring will experience greater impact if precipitation falls as rain instead of snow. We calculated S* (precipitation surplus, which includes

Cultivation of Anaplasma ovis in the HL-60 human promyelocytic leukemia cell line.

PubMed

Wei, Ran; Liu, Hong-Bo; Jongejan, Frans; Jiang, Bao-Gui; Chang, Qiao-Cheng; Fu, Xue; Jiang, Jia-Fu; Jia, Na; Cao, Wu-Chun

2017-09-20

The tick-borne bacterium Anaplasma ovis is a widely distributed pathogen affecting sheep, goats and wild ruminants. Here, the HL-60 human promyelocytic leukemia cell line was used to isolate A. ovis from PCR-positive sheep and goats in Heilongjiang Province, China. Two weeks after inoculation, morulae were observed in cytoplasmic vacuoles in four different HL-60 cultures. Confocal microscopy using a Cy3-labeled A. ovis-specific probe confirmed that the HL-60 cells were infected with A. ovis. Cells from the 6th HL-60 subculture displayed positive fluorescence when incubated with A. ovis antiserum in the indirect fluorescent antibody assay. PCR amplification and sequencing of 16S rRNA, groEL, gltA, msp2 and msp4 Anaplasma genes revealed that the four A. ovis culture isolates were identical. Phylogenetic analysis showed that the sequences clustered with other A. ovis strains but could clearly be distinguished from other Anaplasma species. When the 18th subculture of infected HL-60 cells was examined by electron microscopy, lysosomes were often observed near the vacuoles. After the 24th subculture, Giemsa staining and PCR indicated that the HL-60 cells were negative for A. ovis. Although A. ovis can infect HL-60 cells for only four months, the ability of the organism to infect and multiply in HL-60 cells provides a tool to study intra-erythrocytic Anaplasma and host cell interactions.

Economic Impact of Hearing Loss and Reduction of Noise-Induced Hearing Loss in the United States

ERIC Educational Resources Information Center

Neitzel, Richard L.; Swinburn, Tracy K.; Hammer, Monica S.; Eisenberg, Daniel

2017-01-01

Purpose: Hearing loss (HL) is pervasive and debilitating, and noise-induced HL is preventable by reducing environmental noise. Lack of economic analyses of HL impacts means that prevention and treatment remain a low priority for public health and environmental investment. Method: This article estimates the costs of HL on productivity by building…

Aerodynamic heating environment definition/thermal protection system selection for the HL-20

NASA Astrophysics Data System (ADS)

Wurster, K. E.; Stone, H. W.

1993-09-01

Definition of the aerothermal environment is critical to any vehicle such as the HL-20 Personnel Launch System that operates within the hypersonic flight regime. Selection of an appropriate thermal protection system design is highly dependent on the accuracy of the heating-environment prediction. It is demonstrated that the entry environment determines the thermal protection system design for this vehicle. The methods used to predict the thermal environment for the HL-20 Personnel Launch System vehicle are described. Comparisons of the engineering solutions with computational fluid dynamic predictions, as well as wind-tunnel test results, show good agreement. The aeroheating predictions over several critical regions of the vehicle, including the stagnation areas of the nose and leading edges, windward centerline and wing surfaces, and leeward surfaces, are discussed. Results of predictions based on the engineering methods found within the MINIVER aerodynamic heating code are used in conjunction with the results of the extensive wind-tunnel tests on this configuration to define a flight thermal environment. Finally, the selection of the thermal protection system based on these predictions and current technology is described.

Ascent abort capability for the HL-20

NASA Technical Reports Server (NTRS)

Naftel, J. C.; Talay, T. A.

1993-01-01

The HL-20 has been designed with the capability for rescue of the crew during all phases of powered ascent from on the launch pad until orbital injection. A launch-escape system, consisting of solid rocket motors located on the adapter between the HL-20 and the launch vehicle, provides the thrust that propels the HL-20 to a safe distance from a malfunctioning launch vehicle. After these launch-escape motors have burned out, the adapter is jettisoned and the HL-20 executes one of four abort modes. In three abort modes - return-to-launch-site, transatlantic-abort-landing, and abort-to-orbit - not only is the crew rescued, but the HL-20 is recovered intact. In the ocean-landing-by-parachute abort mode, which occurs in between the return-to-launch-site and the transatlantic-abort-landing modes, the crew is rescued, but the HL-20 would likely sustain damage from the ocean landing. This paper describes the launch-escape system and the four abort modes for an ascent on a Titan III launch vehicle.

Epstein–Barr virus and Hodgkin’s lymphoma in Cairo, Egypt

PubMed Central

Audouin, Josée; Nathwani, Bharat; Ishak, Elia; MacLennan, Kenneth; Mueller-Hermelink, Hans Konrad; Armitage, James O.; Weisenburger, Dennis D.

2010-01-01

Fifty-five consecutive cases of Hodgkin’s lymphoma (HL), collected between 1996 and 1998 from Cairo, Egypt, were histologically subtyped, phenotyped, and then studied for the presence of Epstein–Barr virus (EBV). We used immunohistochemical stains for EBV latent membrane protein 1 (LMP-1) and in situ hybridization stains for EBV-encoded small RNA (EBER-1) transcripts. Forty-five cases (82%) had classic HL (cHL), and ten cases (18%) had nodular lymphocyte predominant HL (NLPHL), with each group expressing its typical phenotype. LMP-1 stains were positive in 63% and 0% of cHL and NLPHL cases, respectively. EBER-positive Reed–Sternberg cells and variants were also present in 62% and 0% of each group, respectively. The cHL cases showed variable EBER positivity: nodular sclerosis, 58%; mixed cellularity, 100%; lymphocyte depletion, 100%; and unclassifiable, 67%. Our findings are similar to those from other developing countries and point towards a pathogenic role of EBV in cHL. PMID:21625283

Ultrastructural localization of human HL-A membrane antigens by use of hybrid antibodies

PubMed Central

Neauport-Sautes, Catherine; Silvestre, Daniele; Niccolai, Marie-Gabrielle; Kourilsky, F. M.; Levy, J. P.

1972-01-01

The localization of HL-A histocompatibility antigens at the surface of human lymphocytes in electron microscopy has been studied using hybrid antibodies to bind electron-dense particles (ferritin and plant viruses) to anti-HL-A antibody. A discontinuous distribution of the markers is observed at the cell surface, which is identical with that described for H-2 antigens on mouse lymphocytes with the same technique. Double labelling experiments suggest that the areas of the cell surface where HL-A antigens are detected contain also the heterologous lymphocyte antigens detected by an anti-thymocyte serum and that HL-A antigens are not renewed at a detectable level during the period of the labelling procedure in the areas of the cell surface which are not labelled primarily with ferritin-anti-IgG-anti-HL-A complexes. The interpretation of the discontinuous labelling of HL-A antigens with direct immunoferritin techniques is discussed. ImagesFIG. 2FIG. 3FIG. 4FIG. 5 PMID:5063188

Associations Between Caregiver Health Literacy and Preschool Children’s Secondhand Smoke Exposure

PubMed Central

Welkom, Josie S.; Riekert, Kristin A.; Rand, Cynthia S.

2016-01-01

Objective Examine the associations between caregiver health literacy (HL) and smoking-related outcome expectancies, implementation of home/car smoking bans (H/CSBs), and child secondhand smoke exposure (SHSe). Methods Caregivers of Head Start children residing with a smoker(s) completed measures assessing HL, outcome expectancies, and H/CSB implementation. Biomarkers of child SHSe included home air nicotine monitors and child salivary cotinine. Results Caregivers with lower HL had higher levels of home air nicotine and child salivary cotinine in the full sample and among smokers. After controlling for child age and number of smokers in the home, lower HL was associated with higher endorsement of negative smoking expectancies in the full sample and in smokers. HL was not associated with H/CSB implementation across groups. Conclusions Caregiver HL is associated with child SHSe and is important in shaping smoking-related beliefs. HL is not directly related to adoption of SHSe-reduction behaviors such as H/CSBs. PMID:26330535

Integration of IEEE 1451 and HL7 exchanging information for patients' sensor data.

PubMed

Kim, Wooshik; Lim, Suyoung; Ahn, Jinsoo; Nah, Jiyoung; Kim, Namhyun

2010-12-01

HL7 (Health Level 7) is a standard developed for exchanging incompatible healthcare information generated from programs or devices among heterogenous medical information systems. At present, HL7 is growing as a global standard. However, the HL7 standard does not support effective methods for treating data from various medical sensors, especially from mobile sensors. As ubiquitous systems are growing, HL7 must communicate with various medical transducers. In the area of sensor fields, IEEE 1451 is a group of standards for controlling transducers and for communicating data from/to various transducers. In this paper, we present the possibility of interoperability between the two standards, i.e., HL7 and IEEE 1451. After we present a method to integrate them and show the preliminary results of this approach.

Subjective health literacy: Development of a brief instrument for school-aged children.

PubMed

Paakkari, Olli; Torppa, Minna; Kannas, Lasse; Paakkari, Leena

2016-12-01

The present paper focuses on the measurement of health literacy (HL), which is an important determinant of health and health behaviours. HL starts to develop in childhood and adolescence; hence, there is a need for instruments to monitor HL among younger age groups. These instruments are still rare. The aim of the project reported here was, therefore, to develop a brief, multidimensional, theory-based instrument to measure subjective HL among school-aged children. The development of the instrument covered four phases: item generation based on a conceptual framework; a pilot study ( n = 405); test-retest ( n = 117); and construction of the instrument ( n = 3853). All the samples were taken from Finnish 7th and 9th graders. Initially, 65 items were generated, of which 32 items were selected for the pilot study. After item reduction, the instrument contained 16 items. The test-retest phase produced estimates of stability. In the final phase a 10-item instrument was constructed, referred to as Health Literacy for School-Aged Children (HLSAC). The instrument exhibited a high Cronbach alpha (0.93), and included two items from each of the five predetermined theoretical components (theoretical knowledge, practical knowledge, critical thinking, self-awareness, citizenship). The iterative and validity-driven development process made it possible to construct a brief multidimensional HLSAC instrument. Such instruments are suitable for large-scale studies, and for use with children and adolescents. Validation will require further testing for use in other countries.

Synthesis, crystal structures and antitumor activities of copper(II) complexes with a 2-acetylpyrazine isonicotinoyl hydrazone ligand

NASA Astrophysics Data System (ADS)

Xu, Jun; Zhou, Tao; Xu, Zhou-Qing; Gu, Xin-Nan; Wu, Wei-Na; Chen, Hong; Wang, Yuan; Jia, Lei; Zhu, Tao-Feng; Chen, Ru-Hua

2017-01-01

Five complexes, [Cu(L)2]·4.5H2O (1), [Cu(HL)2](NO3)2·CH3OH (2) {[Cu2(L)2(NO3)(H2O)2]·(NO3)}n (3), [Cu2(HL)2(SO4)2]·2CH3OH (4) and [Cu4(L)4Cl4]·5H2O (5) based on HL (where HL = 2-acetylpyrazine isonicotinoyl hydrazone) have been synthesized and characterized by X-ray diffraction analyses. The counter anion and organic base during the synthesis procedure influence the structures of the complexes efficiently, which generate five complexes as mono-, bi-, tetra-nuclear and one-dimensional structures. The antitumor activities of the complexes 1-5 (except for complex 3 with the poor solubility) against the Patu8988 human pancreatic cancer, ECA109 human esophagus cancer and SGC7901 human gastric cancer cell lines are screened by MTT assay. The results indicate that the chelation of Cu(II) with the ligand is responsible for the observed high cytotoxicity of the copper(II) complexes and the 1:2 copper species 1 and 2 demonstrate lower antitumor activities than that of the 1:1 copper species 4 and 5. In addition, the in vitro apoptosis inducing activity of the copper(II) complex 5 against SGC7901 cell line is determined. And the results show that the complex can bring about apoptosis of the cancerous cells in vitro.

Specific Mutations in the PB2 Protein of Influenza A Virus Compensate for the Lack of Efficient Interferon Antagonism of the NS1 Protein of Bat Influenza A-Like Viruses.

PubMed

Aydillo, Teresa; Ayllon, Juan; Pavlisin, Amzie; Martinez-Romero, Carles; Tripathi, Shashank; Mena, Ignacio; Moreira-Soto, Andrés; Vicente-Santos, Amanda; Corrales-Aguilar, Eugenia; Schwemmle, Martin; García-Sastre, Adolfo

2018-04-01

Recently, two new influenza A-like viruses have been discovered in bats, A/little yellow-shouldered bat/Guatemala/060/2010 (HL17NL10) and A/flat-faced bat/Peru/033/2010 (HL18NL11). The hemagglutinin (HA)-like (HL) and neuraminidase (NA)-like (NL) proteins of these viruses lack hemagglutination and neuraminidase activities, despite their sequence and structural homologies with the HA and NA proteins of conventional influenza A viruses. We have now investigated whether the NS1 proteins of the HL17NL10 and HL18NL11 viruses can functionally replace the NS1 protein of a conventional influenza A virus. For this purpose, we generated recombinant influenza A/Puerto Rico/8/1934 (PR8) H1N1 viruses containing the NS1 protein of the PR8 wild-type, HL17NL10, and HL18NL11 viruses. These viruses (r/NS1PR8, r/NS1HL17, and r/NS1HL18, respectively) were tested for replication in bat and nonbat mammalian cells and in mice. Our results demonstrate that the r/NS1HL17 and r/NS1HL18 viruses are attenuated in vitro and in vivo However, the bat NS1 recombinant viruses showed a phenotype similar to that of the r/NS1PR8 virus in STAT1 -/- human A549 cells and mice, both in vitro and in vivo systems being unable to respond to interferon (IFN). Interestingly, multiple mouse passages of the r/NS1HL17 and r/NS1HL18 viruses resulted in selection of mutant viruses containing single amino acid mutations in the viral PB2 protein. In contrast to the parental viruses, virulence and IFN antagonism were restored in the selected PB2 mutants. Our results indicate that the NS1 protein of bat influenza A-like viruses is less efficient than the NS1 protein of its conventional influenza A virus NS1 counterpart in antagonizing the IFN response and that this deficiency can be overcome by the influenza virus PB2 protein. IMPORTANCE Significant gaps in our understanding of the basic features of the recently discovered bat influenza A-like viruses HL17NL10 and HL18NL11 remain. The basic biology of these unique viruses displays both similarities to and differences from the basic biology of conventional influenza A viruses. Here, we show that recombinant influenza A viruses containing the NS1 protein from HL17NL10 and HL18NL11 are attenuated. This attenuation was mediated by their inability to antagonize the type I IFN response. However, this deficiency could be compensated for by single amino acid replacements in the PB2 gene. Our results unravel a functional divergence between the NS1 proteins of bat influenza A-like and conventional influenza A viruses and demonstrate an interplay between the viral PB2 and NS1 proteins to antagonize IFN. Copyright © 2018 American Society for Microbiology.

Plant Innate Immunity Induced by Flagellin Suppresses the Hypersensitive Response in Non-Host Plants Elicited by Pseudomonas syringae pv. averrhoi

PubMed Central

Wei, Chia-Fong; Hsu, Shih-Tien; Deng, Wen-Ling; Wen, Yu-Der; Huang, Hsiou-Chen

2012-01-01

A new pathogen, Pseudomonas syringae pv. averrhoi (Pav), which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR) in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta), glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns) contributed to induce the PAMP-triggered immunity (PTI). Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction. PMID:22911741

Plant innate immunity induced by flagellin suppresses the hypersensitive response in non-host plants elicited by Pseudomonas syringae pv. averrhoi.

PubMed

Wei, Chia-Fong; Hsu, Shih-Tien; Deng, Wen-Ling; Wen, Yu-Der; Huang, Hsiou-Chen

2012-01-01

A new pathogen, Pseudomonas syringae pv. averrhoi (Pav), which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR) in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta), glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns) contributed to induce the PAMP-triggered immunity (PTI). Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction.

Targeting functional fitness, hearing and health-related quality of life in older adults with hearing loss: Walk, Talk 'n' Listen, study protocol for a pilot randomized controlled trial.

PubMed

Lambert, Justin; Ghadry-Tavi, Rouzbeh; Knuff, Kate; Jutras, Marc; Siever, Jodi; Mick, Paul; Roque, Carolyn; Jones, Gareth; Little, Jonathan; Miller, Harry; Van Bergen, Colin; Kurtz, Donna; Murphy, Mary Ann; Jones, Charlotte Ann

2017-01-28

Hearing loss (HL) is a disability associated with poorer health-related quality of life including an increased risk for loneliness, isolation, functional fitness declines, falls, hospitalization and premature mortality. The purpose of this pilot trial is to determine the feasibility and acceptability of a novel intervention to reduce loneliness, improve functional fitness, social connectedness, hearing and health-related quality of life in older adults with HL. This 10-week, single-blind, pilot randomized control trial (RCT) will include a convenience sample of ambulatory adults aged 65 years or older with self-reported HL. Following baseline assessments, participants will be randomized to either intervention (exercise, health education, socialization and group auditory rehabilitation (GAR)) or control (GAR only) groups. The intervention group will attend a local YMCA twice a week and the control group once a week. Intervention sessions will include 45 min of strengthening, balance and resistance exercises, 30 min of group walking at a self-selected pace and 60 min of interactive health education or GAR. The control group will attend 60-min GAR sessions. GAR sessions will include education about hearing, hearing technologies, enhancing communication skills, and psychosocial support. Pre-post trial data collection and measures will include: functional fitness (gait speed, 30-s Sit to Stand Test), hearing and health-related quality of life, loneliness, depression, social participation and social support. At trial end, feasibility (recruitment, randomization, retention, acceptability) and GAR will be evaluated. Despite evidence suggesting that HL is associated with declines in functional fitness, there are no studies aimed at addressing functional fitness declines associated with the disability of HL. This pilot trial will provide knowledge about the physical, mental and social impacts on health related to HL as a disability. This will inform the feasibility of a larger RCT and preliminary evidence about the initial effects of a novel, community-based, holistic intervention addressing both the negative psychosocial and functional physical effects of HL among older adults. ClinicalTrials.gov, NCT02662192 . Registered on 14 January 2016.

Lahar flow simulation using Laharz_py program: Application for the Mt. Halla volcano, Jeju, Korea

NASA Astrophysics Data System (ADS)

Chang, C.; Yun, S. H.; Yi, W.

2017-12-01

Lahar, one of catastrophic events, has the potential to cause the loss of life and damage to infrastructure over inhabited areas. This study using Laharz_py, was performed schematic prediction on the impact area of lahar hazards at the Mt. Halla volcano, Jeju island. In order to comprehensively address the impact of lahar for the Mt. Halla, two distinct parameters, H/L ratio and lahar volume, were selected to influence variable for Laharz_py simulation. It was carried out on the basis of numerical simulation by estimating a possible lahar volumes of 30,000, 50,000, 70,000, 100,000, 300,000, 500,000 m3 according to H/L ratios (0.20, 0.22 and 0.25) was applied. Based on the numerical simulations, the area of the proximal hazard zone boundary is gradually decreased with increasing H/L ratio. The number of streams which affected by lahar, tended to decrease with increasing H/L ratio. In the case of H/L ratio 0.20, three streams (Gwangryeong stream, Dogeun stream, Han stream) in the Jeju-si area and six streams (Gungsan stream, Hogeun stream, Seohong stream, Donghong stream, Bomok stream, Yeong stream-Hyodon stream) in the Seogwipo-si area are affected. In the case of H/L ratio 0.22, two streams (Gwangryeong stream and Han stream) in the Jeju-si area and five streams (Gungsan stream, Seohong stream, Donghong stream, Bomok stream, Yeong stream-Hyodon stream) in the Seogwipo-si area are affected. And in the case of H/L ratio 0.25, two streams (Gwangryeong stream and Han stream) in the Jeju-si area and one stream (Yeong stream-Hyodon stream) in the Seogwipo-si area are affected. The results of this study will be used as basic data to create a risk map for the direct damage that can be caused due to volcanic hazards arising from Mt. Halla. This research was supported by a grant [MPSS-NH-2015-81] through the Disaster and Safety Management Institute funded by Ministry of Public Safety and Security of Korean government.

Kinematics and the origin of the internal structures in HL Tauri jet (HH 151)

NASA Astrophysics Data System (ADS)

Movsessian, T. A.; Magakian, T. Yu.; Moiseev, A. V.

2012-05-01

Context. Knotty structures of Herbig-Haro jets are common phenomena, and knowing the origin of these structures is essential for understanding the processes of jet formation. Basically, there are two theoretical approaches: different types of instabilities in stationary flow, and velocity variations in the flow. Aims: We investigate the structures with different radial velocities in the knots of the HL Tau jet as well as its unusual behaviour starting from 20'' from the source. Collation of radial velocity data with proper motion measurements of emission structures in the jet of HL Tau makes it possible to understand the origin of these structures and decide on the mechanism for the formation of the knotty structures in Herbig-Haro flows. Methods: We present observations obtained with a 6 m telescope (Russia) using the SCORPIO camera with scanning Fabry-Perót interferometer. Two epochs of the observations of the HL/XZ Tau region in Hα emission (2001 and 2007) allowed us to measure proper motions for high and low radial velocity structures. Results: The structures with low and high radial velocities in the HL Tau jet show the same proper motion. The point where the HL Tau jet bents to the north (it coincides with the trailing edge of so-called knot A) is stationary, i.e. does not have any perceptible proper motion and is visible in Hα emission only. Conclusions: We conclude that the high- and low-velocity structures in the HL Tau jet represent bow-shocks and Mach disks in the internal working surfaces of episodic outflows. The bend of the jet and the brightness increase starting some distance from the source coincides with the observed stationary deflecting shock. The increase of relative surface brightness of bow-shocks could be the result of the abrupt change of the physical conditions of the ambient medium as well as the interaction of a highly collimated flow and the side wind from XZ Tau. Based on observations collected with the 6 m telescope of the Special Astrophysical Observatory (SAO) of the Russian Academy of Sciences (RAS), operated under the financial support of the Science Department of Russia (registration number 01-43).

Fibroblast growth factor-2 (FGF2) and syndecan-1 (SDC1) are potential biomarkers for putative circulating CD15+/CD30+ cells in poor outcome Hodgkin lymphoma patients

PubMed Central

2013-01-01

Background High risk, unfavorable classical Hodgkin lymphoma (cHL) includes those patients with primary refractory or early relapse, and progressive disease. To improve the availability of biomarkers for this group of patients, we investigated both tumor biopsies and peripheral blood leukocytes (PBL) of untreated (chemo-naïve, CN) Nodular Sclerosis Classic Hodgkin Lymphoma (NS-cHL) patients for consistent biomarkers that can predict the outcome prior to frontline treatment. Methods and materials Bioinformatics data mining was used to generate 151 candidate biomarkers, which were screened against a library of 10 HL cell lines. Expression of FGF2 and SDC1 by CD30+ cells from HL patient samples representing good and poor outcomes were analyzed by qRT-PCR, immunohistochemical (IHC), and immunofluorescence analyses. Results To identify predictive HL-specific biomarkers, potential marker genes selected using bioinformatics approaches were screened against HL cell lines and HL patient samples. Fibroblast Growth Factor-2 (FGF2) and Syndecan-1 (SDC1) were overexpressed in all HL cell lines, and the overexpression was HL-specific when compared to 116 non-Hodgkin lymphoma tissues. In the analysis of stratified NS-cHL patient samples, expression of FGF2 and SDC1 were 245 fold and 91 fold higher, respectively, in the poor outcome (PO) group than in the good outcome (GO) group. The PO group exhibited higher expression of the HL marker CD30, the macrophage marker CD68, and metastatic markers TGFβ1 and MMP9 compared to the GO group. This expression signature was confirmed by qualitative immunohistochemical and immunofluorescent data. A Kaplan-Meier analysis indicated that samples in which the CD30+ cells carried an FGF2+/SDC1+ immunophenotype showed shortened survival. Analysis of chemo-naive HL blood samples suggested that in the PO group a subset of CD30+ HL cells had entered the circulation. These cells significantly overexpressed FGF2 and SDC1 compared to the GO group. The PO group showed significant down-regulation of markers for monocytes, T-cells, and B-cells. These expression signatures were eliminated in heavily pretreated patients. Conclusion The results suggest that small subsets of circulating CD30+/CD15+ cells expressing FGF2 and SDC1 represent biomarkers that identify NS-cHL patients who will experience a poor outcome (primary refractory and early relapsing). PMID:23988031

HL-10 on ramp

NASA Technical Reports Server (NTRS)

1966-01-01

The HL-10, seen here parked on the ramp at NASA's Flight Research Center in 1966, had a radically different shape from that of the M2-F2/F3. While the M2s were flat on top and had rounded undersides (giving them a bathtub shape), the HL-10 had a flat lower surface and a rounded top. Both shapes provided lift without wings, however. This photo was taken before the HL-10's fins were modified. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. The vehicle was unstable and required modifications to its fins to improve its handling qualities and stability. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

HL-10 first flight landing

NASA Technical Reports Server (NTRS)

1966-01-01

The HL-10 Lifting Body completes its first research flight with a landing on Rogers Dry Lake at Edwards AFB, California, on December 22, 1966. The HL-10 suffered from buffeting and poor control during the flight. Pilot Bruce Peterson was able to make a successful landing despite the severe problems. These were traced to airflow separation from the fins. As a result, the fins were no longer able to stabilize the vehicle. A small reshaping of the fins' leading edges cured the airflow separation, but it was not until March 15, 1968, that the second HL-10 flight occurred. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

HL-10 in flight over lakebed

NASA Technical Reports Server (NTRS)

1969-01-01

The HL-10 Lifting Body is seen here in flight over Rogers Dry lakebed. Like the other lifting bodies, the HL-10 made a steep descent toward the lakebed, followed by a high-speed landing. This was due to the vehicle's low lift-over-drag ratio. The first 11 flights of the HL-10 were unpowered, flown to check the vehicle's handling and stability before rocket-powered flights began using the XLR-11 rocket engine. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

HL-10 in flight after launch

NASA Technical Reports Server (NTRS)

1969-01-01

The HL-10 Lifting Body is seen here in powered flight shortly after launch from the B-52 mothership. When HL-10 powered flights began on October 23, 1968, the vehicle used the same basic XLR-11 rocket engine that powered the original X-1s. A total of five powered flights were made before the HL-10 first flew supersonically on May 9, 1969, with John Manke in the pilot's seat. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

HL-10 on lakebed with pilot Major Jerauld R. Gentry

NASA Technical Reports Server (NTRS)

1968-01-01

Pilot Major Jerauld R. Gentry stands in front of the HL-10 Lifting Body. Gentry was the Air Force project pilot for the HL-10 while it was making the early glide and powered flights in 1968 following its modification. He made a total of nine flights in the vehicle. For his work on the HL-10, Gentry was awarded the Harmon International Trophy for his outstanding contribution to the science of flying. He later became the Air Force pilot for the X-24A. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

HL-10 on lakebed with pilot Bill Dana

NASA Technical Reports Server (NTRS)

1969-01-01

This photo shows the HL-10 on Rogers Dry Lakebed with pilot Bill Dana in the foreground. Bill joined the HL-10 program in 1969 after flying the M2-F1 and the X-15, among other aircraft. His first glide flight was on April 25, 1969. Some months later, on September 3, 1969, he reached an altitude of 77,960 feet. This was one of a series of HL-10 flights to collect stability and control data at higher speeds and altitudes and at different angles of attack. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Multilingual Identity Development and Negotiation Amongst Heritage Language Learners: A Study of East European-American Schoolchildren in the United States

ERIC Educational Resources Information Center

Seals, Corinne A.

2013-01-01

Previous research in the field of heritage language (HL) acquisition has focused on the connection between frequency of language use and HL speakers' connection to and maintenance of their HL. This dissertation introduces the concept of positioning through discourse into the study of HLs to show evidence that while frequency of HL use contributes…

HL-10 mounted on a pedestal in front of the Dryden main gate at sunset

NASA Technical Reports Server (NTRS)

1992-01-01

The HL-10 Lifting Body, as shown here, is currently displayed on a pedestal in front of the main gate at NASA's Dryden Flight Research Center, Edwards, California. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Survey of health literacy level and related influencing factors in military college students in Chongqing, China: A cross-sectional analysis.

PubMed

Rong, Honghui; Cheng, Xin; Garcia, Jose M; Zhang, Ling; Lu, Lu; Fang, Jian; Le, Mingshan; Hu, Peng; Dong, Xinlu; Yang, Junli; Wang, Ya; Luo, Ting; Liu, Jun; Chen, Ji-An

2017-01-01

Health literacy (HL) has become an important public health issue and is receiving growing attention. However, the HL levels of military college students in China have never been analyzed. This study aimed to investigate the HL and related associate factors in military college students in Chongqing, China. Data was obtained with the "Chinese Citizen Health Literacy Questionnaire (2012 edition)" from 3183 military college students aged 16-28 years at Chongqing in December 2015. A total score of ≥80 points determined adequate HL, and HL level was defined as the proportion of students who had adequate HL out of the total number of participants. Multiple logistic regression analysis with a stepwise forward likelihood ratio (LR) method was used to determine the effects of sociodemographic characteristics, health-related behaviors, and family-related factors on HL level. The mean score of HL was 68.56, and the HL level of military college students was 21.05%; the overall knowledge rate was 71.33%. The independent factors that were associated with HL level were years in college, educational system, time playing online games, annual household income and father's education level. Senior (odds ratio [OR] = 1.229, 95% confidence interval [CI] 1.018∼1.484), undergraduate (OR = 1.509, 95% CI 1.151∼1.978), time played games more than 5 hours each week (OR = 0.638, 95% CI 0.486∼0.837), annual household incomes more than 50,000 yuan (OR = 1.231, 95% CI 1.027∼1.476) and father's education level (high school: OR = 2.327, 95% CI 1.186∼4.565; university: OR = 2.450, 95% CI 1.244∼4.825), were independently associated with higher HL level. HL levels of military college students in Chongqing need to be improved across the board. Our data suggests that special emphasis should be placed on students in junior and those in the specialist educational system. School departments may also benefit from incorporating health literacy into their curricula and helping students manage the time they spend playing online games.

Survey of health literacy level and related influencing factors in military college students in Chongqing, China: A cross-sectional analysis

PubMed Central

Rong, Honghui; Cheng, Xin; Garcia, Jose M.; Zhang, Ling; Lu, Lu; Fang, Jian; Le, Mingshan; Hu, Peng; Dong, Xinlu; Yang, Junli; Wang, Ya; Luo, Ting; Liu, Jun

2017-01-01

Health literacy (HL) has become an important public health issue and is receiving growing attention. However, the HL levels of military college students in China have never been analyzed. This study aimed to investigate the HL and related associate factors in military college students in Chongqing, China. Data was obtained with the “Chinese Citizen Health Literacy Questionnaire (2012 edition)” from 3183 military college students aged 16–28 years at Chongqing in December 2015. A total score of ≥80 points determined adequate HL, and HL level was defined as the proportion of students who had adequate HL out of the total number of participants. Multiple logistic regression analysis with a stepwise forward likelihood ratio (LR) method was used to determine the effects of sociodemographic characteristics, health-related behaviors, and family-related factors on HL level. The mean score of HL was 68.56, and the HL level of military college students was 21.05%; the overall knowledge rate was 71.33%. The independent factors that were associated with HL level were years in college, educational system, time playing online games, annual household income and father's education level. Senior (odds ratio [OR] = 1.229, 95% confidence interval [CI] 1.018∼1.484), undergraduate (OR = 1.509, 95% CI 1.151∼1.978), time played games more than 5 hours each week (OR = 0.638, 95% CI 0.486∼0.837), annual household incomes more than 50,000 yuan (OR = 1.231, 95% CI 1.027∼1.476) and father's education level (high school: OR = 2.327, 95% CI 1.186∼4.565; university: OR = 2.450, 95% CI 1.244∼4.825), were independently associated with higher HL level. HL levels of military college students in Chongqing need to be improved across the board. Our data suggests that special emphasis should be placed on students in junior and those in the specialist educational system. School departments may also benefit from incorporating health literacy into their curricula and helping students manage the time they spend playing online games. PMID:28545133

HL-10 on ramp

NASA Technical Reports Server (NTRS)

1966-01-01

The HL-10, seen here parked on the ramp, was one of five lifting body designs flown at NASA's Dryden Flight Research Center, Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Combining Archetypes with Fast Health Interoperability Resources in Future-proof Health Information Systems.

PubMed

Bosca, Diego; Moner, David; Maldonado, Jose Alberto; Robles, Montserrat

2015-01-01

Messaging standards, and specifically HL7 v2, are heavily used for the communication and interoperability of Health Information Systems. HL7 FHIR was created as an evolution of the messaging standards to achieve semantic interoperability. FHIR is somehow similar to other approaches like the dual model methodology as both are based on the precise modeling of clinical information. In this paper, we demonstrate how we can apply the dual model methodology to standards like FHIR. We show the usefulness of this approach for data transformation between FHIR and other specifications such as HL7 CDA, EN ISO 13606, and openEHR. We also discuss the advantages and disadvantages of defining archetypes over FHIR, and the consequences and outcomes of this approach. Finally, we exemplify this approach by creating a testing data server that supports both FHIR resources and archetypes.

Design and construction of high-frequency magnetic probe system on the HL-2A tokamak

NASA Astrophysics Data System (ADS)

Liang, S. Y.; Ji, X. Q.; Sun, T. F.; Xu, Yuan; Lu, J.; Yuan, B. S.; Ren, L. L.; Yang, Q. W.

2017-12-01

A high-frequency magnetic probe system is designed, calibrated and constructed on the HL-2A tokamak. To investigate the factors which affect the probe frequency response, the inductance and capacitance in the probe system are analyzed using an equivalent circuit. Suitable sizes and turn number of the coil, and the length of transmission cable are optimized based on the theory and detailed test in the calibration. To deal with the frequency response limitation and bake-out, the ceramic grooved technique is used and the probe is wound with a bare copper wire. A cascade filter is manufactured with a suitable bandwidth as well as a good phase consistency between channels. The system has been used in the experiment to measure high frequency (≤300 kHz) magnetohydrodynamic fluctuations, which can meet the requirement of physical analysis on HL-2A.

Radiation Hard Silicon Particle Detectors for Phase-II LHC Trackers

NASA Astrophysics Data System (ADS)

Oblakowska-Mucha, A.

2017-02-01

The major LHC upgrade is planned after ten years of accelerator operation. It is foreseen to significantly increase the luminosity of the current machine up to 1035 cm-2s-1 and operate as the upcoming High Luminosity LHC (HL-LHC) . The major detectors upgrade, called the Phase-II Upgrade, is also planned, a main reason being the aging processes caused by severe particle radiation. Within the RD50 Collaboration, a large Research and Development program has been underway to develop silicon sensors with sufficient radiation tolerance for HL-LHC trackers. In this summary, several results obtained during the testing of the devices after irradiation to HL-LHC levels are presented. Among the studied structures, one can find advanced sensors types like 3D silicon detectors, High-Voltage CMOS technologies, or sensors with intrinsic gain (LGAD). Based on these results, the RD50 Collaboration gives recommendation for the silicon detectors to be used in the detector upgrade.

Stego on FPGA: An IWT Approach

PubMed Central

Ramalingam, Balakrishnan

2014-01-01

A reconfigurable hardware architecture for the implementation of integer wavelet transform (IWT) based adaptive random image steganography algorithm is proposed. The Haar-IWT was used to separate the subbands namely, LL, LH, HL, and HH, from 8 × 8 pixel blocks and the encrypted secret data is hidden in the LH, HL, and HH blocks using Moore and Hilbert space filling curve (SFC) scan patterns. Either Moore or Hilbert SFC was chosen for hiding the encrypted data in LH, HL, and HH coefficients, whichever produces the lowest mean square error (MSE) and the highest peak signal-to-noise ratio (PSNR). The fixated random walk's verdict of all blocks is registered which is nothing but the furtive key. Our system took 1.6 µs for embedding the data in coefficient blocks and consumed 34% of the logic elements, 22% of the dedicated logic register, and 2% of the embedded multiplier on Cyclone II field programmable gate array (FPGA). PMID:24723794

New metal-organic complexes based on bis(tetrazole) ligands: Synthesis, structures and properties

NASA Astrophysics Data System (ADS)

Du, Ceng-Ceng; Fan, Jian-Zhong; Wang, Xin-Fang; Zhou, Sheng-Bin; Wang, Duo-Zhi

2017-04-01

In this paper, a series of new complexes, [Zn2(HL1)2(H2O)4]·H2O (1), [Co2(HL1)2]·TEA (2), [Co3(HL1)2(H2L1)2(H2O)4]n (3), [Cu(HL1)(H2O)2]n (4), {[Cu5(HL2)2(OH)4(ClO4)2]·4H2O}n (5) and [Cu2(L3)]n (6) were successfully prepared by utilizing three bis(tetrazole) ligands [bis-(1H-tetrazol-5-ylmethyl)-amine (H3L1), bis-(1H-tetrazol-5-ylethyl)-amine (H3L2) and 1,5-bis(5-tetrazolo)-3-thiapentane (H2L3)], all of which have been characterized by elemental analyses, FT-IR spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analyses as well as single-crystal X-ray diffraction analyses showing different dimensionalities (0D, 1D and 3D). Complexes 1 and 2 are 0D structures, 1 shows a dinuclear structure, 2 displays two crystallographically different mononuclear structures, 1 and 2 are further assembled to form 3D supramolecular framework and 2D supramolecular network by hydrogen-bonding interactions, respectively. Complexes 3, 4 and 5 are 1D structures, 3 features a mononuclear unit and a 1D chain, which are arranged into 3D supramolecular architecture by hydrogen-bonding interactions, 4 presents a zigzag chain, 5 shows an infinite chain structure constructed from pentanuclear Cu(II) subunits and ClO4- anions. Complex 6 exhibits a 3D coordination framework based on cyclic [Cu4(L3)2] dimmer subunits as nodes possessing an 8-connected network topology with the point symbol {424·64}. Further, semiconductor behaviors, the solid-state luminescent properties of the complexes 1-3 and 6 were measured and studied seriously at room temperature.

Hodgkin lymphoma incidence in California Hispanics: Influence of nativity and tumor Epstein–Barr virus

PubMed Central

Clarke, C. A.; Chang, E. T.; Yang, J.; Gomez, S. L.; Keegan, T. H.

2017-01-01

Purpose For classical Hodgkin lymphoma (HL), migrant studies could elucidate contributions of environmental factors (including Epstein–Barr virus (EBV)) to the lower rates in non-whites. Given the well-described etiologic complexity of HL, this research requires a large, immigrant population, such as California Hispanics. Methods With 1988–2004 California Cancer Registry data (2,595 Hispanic, 8,637 white HL cases) and tumor cell EBV status on a subset (218 Hispanics, 656 whites), we calculated ethnicity- and nativity-specific HL incidence rates simultaneously by age, sex, and histologic subtype, and tumor cell EBV prevalence. Results Compared with white rates, Hispanic HL rates were lower overall (70 %) and for nodular sclerosis HL, particularly among young adults (60–65 % for females). However, they were higher among children (200 %) and older adults, and for mixed cellularity HL. Compared with rates in foreign-born Hispanics, rates in US-born Hispanics were higher among young adults (>threefold in females), lower for children and adults over age 70, and consistently intermediate compared with rates in whites. EBV tumor prevalence was 67, 32, and 23 % among foreign-born Hispanics, US-born Hispanics, and whites, respectively, although with variation by age, sex, and histology. Conclusions Findings strongly implicate environmental influences, such as nativity-related sociodemographic differences, on HL occurrence. In addition, lower young adult rates and higher EBV prevalence in US-born Hispanics than in whites raise questions about the duration/extent of environmental change for affecting HL rates and also point to ethnic differences in genetic susceptibility. Lesser variation in mixed cellularity HL rates and greater variation in rates for females across groups suggest less modifiable factors interacting with environmental influences. PMID:24722952

Alterations of CHEK2 forkhead-associated domain increase the risk of Hodgkin lymphoma.

PubMed

Havranek, O; Spacek, M; Hubacek, P; Mocikova, H; Markova, J; Trneny, M; Kleibl, Z

2011-01-01

Checkpoint kinase 2 gene (CHEK2) codes for an important mediator of DNA damage response pathway. Mutations in the CHEK2 gene increase the risk of several cancer types, however, their role in Hodgkin lymphoma (HL) has not been studied so far. The most frequent CHEK2 alterations (including c.470T>C; p.I157T) cluster into the forkhead-associated (FHA) domain-coding region of the CHEK2 gene. We performed mutation analysis of the CHEK2 gene segment coding for FHA domain using denaturing high-performance liquid chromatography in 298 HL patients and analyzed the impact of characterized CHEK2 gene variants on the risk of HL development and progression-free survival (PFS). The overall frequency of CHEK2 alterations was significantly higher in HL patients (17/298; 5.7%) compared to the previously analyzed non-cancer controls (19/683; 2.8%; p= 0.04). Presence of any alteration within the analyzed region of the CHEK2 gene was associated with increased risk of HL development (OR = 2.11; 95% CI = 1.08 - 4.13; p= 0.04). The most frequent I157T mutation was found in 4.0% of HL patients and 2.5% of controls (p = 0.22), however, the frequency of 5 other alterations (excluding I157T) was significantly higher in HL cases and associated with increased risk of HL development (OR = 5.81; 95% CI = 1.12 - 30.12; p= 0.03). PFS in HL patients did not differ between CHEK2 mutation carriers and non-carriers. The predominant I157T mutation together with other alterations in its proximity represent moderate genetic predisposition factor increasing the risk of HL development.

Differentiation of HL-60 cells distinguishes between cytostatic and cytotoxic effects of the alkylphospholipid ET-18-OCH3.

PubMed

Civoli, F; Pauig, S B; Daniel, L W

1996-01-01

The synthetic dialkylphospholipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) inhibits growth of the acute myelogenous leukemia cell line HL-60. Incubation of HL-60 cells with demethyl-sulfoxide causes the cells to differentiate to a granulocyte-like phenotype and become quiescent. Incubation of the DMSO-treated cells with ET-18-OCH3 results in a reduction in cell numbers due to cytotoxicity. In contrast, treatment of undifferentiated HL-60 cells with lower concentrations of ET-18-OCH3 leads to growth inhibition. These data indicate that the model of differentiated HL-60 cells currently used for the study of resistance to growth inhibition is inappropriate. HL-60 cells can be used to measure growth inhibition and at higher doses cytotoxicity. However, the differentiated, nonproliferative, cells can only be used to measure direct cytotoxicity. Therefore, the results of studies directly comparing the effects of ET-18-OCH3 in proliferative HL-60 cells and quiescent DMSO-treated HL-60 cells should be reevaluated. An evaluation of the effects of low concentrations of ET-18-OCH3 (0.5-1.5 microM) in proliferative HL-60 cells indicated that ET-18-OCH3 was an effective cytostatic agent at nontoxic concentrations. In summary, studies on the mechanism of action of ET-18-OCH3, or related ether lipids, should carefully investigate differences in the effects at cytostatic versus cytotoxic concentrations.

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

Laouar, A.; Glesne, D.; Huberman, E.

The role of protein kinase C-{beta} (PKC-{beta}) in apoptosis induced by tumor necrosis factor (TNF)-{alpha} and anti-Fas monoclonal antibody (mAb) in the human myeloid HL-60 leukemia cell line was studied by using its variant HL-525, which is deficient in PKC-{beta}. In contrast to the parental HL-60 cells, HL-525 is resistant to TNF-{alpha}-induced apoptosis but sensitive to anti-Fas mAb-induced apoptosis. Both cell types expressed similar levels of the TNF-receptor I, whereas the Fas receptor was detected only in HL-525 cells. Transfecting the HL-525 cells with an expression vector containing PKC-{beta} reestablished their susceptibility to TNF-{alpha}-induced apoptosis. The apoptotic effect of TNF-{alpha}more » in HL-60 and the transfectants was abrogated by fumonisin, an inhibitor of ceramide generation, and by the peptide Ac-YVAD-BoMK, an inhibitor of caspase-1 and -4. Supplementing HL-525 cells with exogenous ceramides bypassed the PKC-{beta} deficiency and induced apoptosis, which was also restrained by the caspase-1 and -4 inhibitor. The apoptotic effect of anti-Fas mAb in HL-525 cells was abrogated by the antioxidants N-acetylcysteine and glutathione and by the peptide z-DEVD-FMK, an inhibitor of caspase-3 and -7. We suggest that TNF-{alpha}-induced apoptosis involves PKC-{beta} and then ceramide and, in turn, caspase-1 and/or -4, whereas anti-Fas mAb-induced apoptosis utilizes reactive oxygen intermediates and, in turn, caspase-3 and/or -7.« less

A photophysical study of two fluorogen-activating proteins bound to their cognate fluorogens

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

Gaiotto, Tiziano; Nguyen, Hau B; Jung, Jaemyeong

We are exploring the feasibility of using recently developed flu orogen-activating proteins (FAPs) as reporters for single-molecule imaging. FAPs are single-chain antibodies choosen to specifically bind small chromophoric molecules termed f1uorogens. Upon binding to its cognate FAP the fluorescence quantum yield of the fluorogen can increase substantially giving rise to a fluorescent complex. Based on the seminal work of Szent-Gyorgyi et al. (Nature Biotechnology, Volume 26, Number 2, pp 235-240, 2008) we have chosen to study two fluorogen-activating single-chain antibodies, HL 1.0.1-TOI and H6-MG bound to their cognate fluorogens, thiazole orange and malachite green derivatives, respectively. Here we use fluorescencemore » correlation spectroscopy study the photophysics of these fluorescent complexes.« less

Metabolic changes and induction of hepatic lipidosis during feed restriction in llamas.

PubMed

Tornquist, S J; Cebra, C K; Van Saun, R J; Smith, B B; Mattoon, J S

2001-07-01

To determine whether feed restriction induces hepatic lipidosis (HL) in llamas and to evaluate the metabolic changes that develop during feed restriction. 8 healthy adult female llamas. Llamas were fed grass hay at a rate of 0.25% of their body weight per day for 13 to 28 days. Llamas were monitored by use of clinical observation, serum biochemical analyses, and ultrasound-guided liver biopsies. All 8 llamas lost weight and mobilized fat. Five llamas developed HL, including 4 that were nursing crias. During the period of feed restriction, mean serum concentration of bile acids and activities of aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), and gamma-glutamyl transferase (GGT) were significantly higher in llamas that developed HL, compared with llamas that did not. Mean insulin-to-cortisol concentration ratios were lower in llamas with HL before and up to 7 days of feed restriction, compared with those that did not develop HL. HL in llamas may be induced by severe feed restriction, particularly in the face of increased energy demand. Llamas with weight loss attributable to inadequate dietary intake may develop biochemical evidence of hepatopathy and HL. Increases in serum concentration of bile acids and activities of GGT, AST, and SDH may indicate the development of HL in llamas and identify affected animals for aggressive therapeutic intervention.

Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis

PubMed Central

Glaser, Sally L.; Schupp, Clayton W.; Ekström Smedby, Karin; de Sanjosé, Silvia; Kane, Eleanor; Melbye, Mads; Forétova, Lenka; Maynadié, Marc; Staines, Anthony; Becker, Nikolaus; Nieters, Alexandra; Brennan, Paul; Boffetta, Paolo; Cocco, Pierluigi; Glimelius, Ingrid; Clavel, Jacqueline; Hjalgrim, Henrik; Chang, Ellen T.

2013-01-01

Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inverse associations with HL risk for UVR exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant dose-response relationships. Risks were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95% confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category), with a significant linear trend for overall exposure (P = .03). Pooled relative risk estimates were not heterogeneous across studies. Increased UVR exposure may protect against HL, particularly EBV-positive HL. Plausible mechanisms involving UVR induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets. PMID:24016459

Maximum likelihood identification and optimal input design for identifying aircraft stability and control derivatives

NASA Technical Reports Server (NTRS)

Stepner, D. E.; Mehra, R. K.

1973-01-01

A new method of extracting aircraft stability and control derivatives from flight test data is developed based on the maximum likelihood cirterion. It is shown that this new method is capable of processing data from both linear and nonlinear models, both with and without process noise and includes output error and equation error methods as special cases. The first application of this method to flight test data is reported for lateral maneuvers of the HL-10 and M2/F3 lifting bodies, including the extraction of stability and control derivatives in the presence of wind gusts. All the problems encountered in this identification study are discussed. Several different methods (including a priori weighting, parameter fixing and constrained parameter values) for dealing with identifiability and uniqueness problems are introduced and the results given. The method for the design of optimal inputs for identifying the parameters of linear dynamic systems is also given. The criterion used for the optimization is the sensitivity of the system output to the unknown parameters. Several simple examples are first given and then the results of an extensive stability and control dervative identification simulation for a C-8 aircraft are detailed.

Mannich bases of 1,2,4-triazole-3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies.

PubMed

Milošev, Milorad Z; Jakovljević, Katarina; Joksović, Milan D; Stanojković, Tatjana; Matić, Ivana Z; Perović, Milka; Tešić, Vesna; Kanazir, Selma; Mladenović, Milan; Rodić, Marko V; Leovac, Vukadin M; Trifunović, Snežana; Marković, Violeta

2017-06-01

A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-thione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells. The effects of compounds 5b, 5e, and 5j on the cell cycle were investigated by flow cytometric analysis. It was found that these compounds cause the accumulation of cells in the subG1 and G1 phases of the cell cycle and induce caspase-dependent apoptosis, while the anti-angiogenic effects of 5b, 5e, and 5j have been confirmed in EA.hy926 cells using a tube formation assay. Further, the interaction of Bax protein with compound 5b was investigated by means of molecular modeling, applying the combined molecular docking/molecular dynamics approach. © 2016 John Wiley & Sons A/S.

Serum free amino acid concentration in hepatic lipidosis of dairy cows in the periparturient period.

PubMed

Shibano, Ken-ichi; Kawamura, Seiichi

2006-04-01

Blood samples were taken from eight multiparous cows at a dairy farm on eight occasions between the prepartum period and peak lactation to study the serum concentrations of amino acids and biochemical constituents. The cows were classified as having either severe hepatic lipidosis (HL) or non-hepatic lipidosis (non-HL) according to their clinical condition after calving and changes in serum biochemical parameters. The serum concentrations of beta-hydroxybutyric acid were higher in the HL group than in the non-HL group (ANOVA: p<0.01). The serum concentrations of methionine (Met), phenylalanine, and arginine were significantly different between the two groups (ANOVA: p<0.05). In particular, the Met levels were significantly low for 14 days after calving in the HL group (p<0.05), although Met levels in the HL group tended to be lower than the values in the non-HL group until 30 days after calving, starting 14 days before calving. The results suggest that an insufficiency of Met during the periparturient period is related to the development of hepatic lipidosis.

Risk of Hodgkin lymphoma according to immigration status and origin: a migrant cohort study of 2.3 million Jewish Israelis.

PubMed

Levine, Hagai; Leiba, Merav; Bar Zeev, Yael; Keinan-Boker, Lital; Derazne, Estela; Leiba, Adi; Kark, Jeremy D

2017-04-01

Hodgkin Lymphoma (HL), a common early adulthood malignancy, has a complex etiology. We conducted a migrant cohort study to assess immigration status and origin as predictors of HL in Israel, which has among the highest rates of HL worldwide. Nationwide data on 2,285,009 16-19-year-old Jewish adolescents, collected from 1967-2011, were linked to Israel's Cancer Registry to obtain the incidence of HL until 2012. Two thousand and ninety-three HL cases were detected during 47.0 million person-years of follow-up. Using multivariable-adjusted Cox proportional hazards modeling, risk was higher for Israeli-born compared to immigrants, similarly across origin groups (HR = 1.59; 95%CI 1.32-1.92 for the dominant nodular sclerosis subtype). Risk of HL was greater for more recent year of birth, higher BMI, taller stature, and apparently for women. These findings suggest that exposure to as yet unidentified elements of the Israeli environment increase the risk of nodular sclerosis HL, and should aid in directing research efforts.

Associations Between Caregiver Health Literacy and Preschool Children's Secondhand Smoke Exposure.

PubMed

Welkom, Josie S; Riekert, Kristin A; Rand, Cynthia S; Eakin, Michelle N

2016-05-01

Examine the associations between caregiver health literacy (HL) and smoking-related outcome expectancies, implementation of home/car smoking bans (H/CSBs), and child secondhand smoke exposure (SHSe). Caregivers of Head Start children residing with a smoker(s) completed measures assessing HL, outcome expectancies, and H/CSB implementation. Biomarkers of child SHSe included home air nicotine monitors and child salivary cotinine. Caregivers with lower HL had higher levels of home air nicotine and child salivary cotinine in the full sample and among smokers. After controlling for child age and number of smokers in the home, lower HL was associated with higher endorsement of negative smoking expectancies in the full sample and in smokers. HL was not associated with H/CSB implementation across groups. Caregiver HL is associated with child SHSe and is important in shaping smoking-related beliefs. HL is not directly related to adoption of SHSe-reduction behaviors such as H/CSBs. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

New eremophilane-type sesquiterpenes from an Antarctic deepsea derived fungus, Penicillium sp. PR19 N-1.

PubMed

Lin, Aiqun; Wu, Guangwei; Gu, Qianqun; Zhu, Tianjiao; Li, Dehai

2014-07-01

Chemical investigation of an Antarctic deepsea derived fungus Penicillium sp. PR19 N-1 yielded five new eremophilane-type sesquiterpenes 1–5 and a new rare lactam-type eremophilane 6, together with three known compounds 7–9. The structures of these diverse sesquiterpenes were determined by extensive NMR and mass spectroscopic analyses. Compounds 1, 2, 4–6, 8 and 9 were evaluated for their cytotoxities against HL-60 and A-549 human cancer cell lines, and 5 was the most active one with IC50 value of 5.2 lM against the A-549 cells.

Zn(II), Ni(II), Cu(II) and Pb(II) complexes of tridentate asymmetrical Schiff base ligands: Synthesis, characterization, properties and biological activity

NASA Astrophysics Data System (ADS)

Şahin, Mustafa; Koçak, Nuriye; Erdenay, Damla; Arslan, Uğur

2013-02-01

New asymmetrical tridentate Schiff base ligands were synthesized using 1,2-phenylenediamine, 4-methyl-1,2-phenylenediamine, 2-hydroxy-1-napthaldehyde, 9-anthracenecarboxaldehyde. Schiff base ligands and their metal complexes were synthesised and characterized by using FT-IR, 1H NMR, 13C NMR, UV-Vis, XRD, ESR, elemental analysis and fluorescence studies. The antimicrobial activity of the ligands and their metal complexes were studied against Staphylococcus aureus ATCC 29213, S. aureus ATCC 25923, Streptococcus mutans RSHM 676, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853. The determination of the antibacterial activity was done using the broth microdilution methods. In general, it has been determined that the studied compounds have MIC values similar to Gram-positive and Gram-negative bacteria. It has been found that Ni, Pb, Zn derivatives of HL1A and ZnL2A has lower MIC values than ampicillin for P. aeruginosa ATCC 27853 strain.

Is HL Tauri and FU Orionis system in quiescence?

NASA Technical Reports Server (NTRS)

Lin, D. N. C.; Hayashi, M.; Bell, K. R.; Ohashi, N.

1994-01-01

A recent Nobeyama map of HL Tau reveals that gas is infalling in a flattened region approximately 1400 AU around the central star. The apparent motion of the gas provides the necessary condition for the formation of a Keplerian disk with a radius comparable to the size of the primordial solar nebula. The inferred mass infall rate onto the disk is approximately equal to 5 x 10(exp -6) solar mass/yr, which greatly exceeds the maximum estimate of the accretion rate onto the central star (approximately 7 x 10(exp -7) solar mass/yr). Consequently, mass must currently be accumulating in the disk. The estimated age and disk mass of HL Tau suggest that the accumulated matter has been flushed repeatedly on a timescale less than 10(exp 4) yr. Based on the similarites between their evolution patterns, we propose that HL Tau is an FU Orionis system in quiescence. In addition to HL Tau, 14 out of 86 pre-main-sequence stars in the Taurus-Auriga dark clouds have infrared luminosities much greater than their otherwise normal extinction-corrected stellar luminosities. These sources also tend to have flat spectra which may be due to the reprocessing of radiation by dusty, flattened, collapsing envelopes with infall rates a few 10(exp -6) solar mass/yr. Such rates are much larger than estimated central accretion rates for these systems, which suggests that mass must also be accumulating in these disks. If these sources are FU Orionis stars in quiescence, similar to HL Tau, their age and relative abundance imply that the FU Orionis phase occurs over a timescale of approixmately 10(exp 5) yr, and the quiescent phase between each outburst lasts approximately 10(exp 3) =10(exp 4) yr. These inferred properties are compatible with the scenario that FU Orionis outbursts are regulated by a thermal instability in the inner region of the disk.

Patient-reported outcome measures (PROMs) for assessing perceived listening effort in hearing loss: protocol for a systematic review

PubMed Central

Rapport, Frances L; Boisvert, Isabelle; McMahon, Catherine M; Hutchings, Hayley A

2017-01-01

Introduction In the UK, it is estimated that a disabling hearing loss (HL) affects 1 in 6 people. HL has functional, economic and social-emotional consequences for affected individuals. Intervention for HL focuses on improving access to the auditory signal using hearing aids or cochlear implants. However, even if sounds are audible and speech is understood, individuals with HL often report increased effort when listening. Listening effort (LE) may be measured using self-reported measures such as patient-reported outcome measures (PROMs). PROMs are validated questionnaires completed by patients to measure their perceptions of their own functional status and well-being. When selecting a PROM for use in research or clinical practice, it is necessary to appraise the evidence of a PROM’s acceptability to patients, validity, responsiveness and reliability. Methods and analysis A systematic review of studies evaluating the measurement properties of PROMs available to measure LE in HL will be undertaken. MEDLINE, EMBASE, CINAHL, PsychINFO and Web of Science will be searched electronically. Reference lists of included studies, key journals and the grey literature will be hand-searched to identify further studies for inclusion. Two reviewers will independently complete title, abstract and full-text screening to determine study eligibility. Data on the characteristics of each study and each PROM will be extracted. Methodological quality of the included studies will be appraised using the COnsensus-based Standards for the selection of health Measurement INstruments, the quality of included PROMs appraised and the credibility of the evidence assessed. A narrative synthesis will summarise extracted data. Ethics and dissemination Ethical permission is not required, as this study uses data from published research. Dissemination will be through publication in peer-reviewed journals, conference presentations and the lead author’s doctoral dissertation. Findings may inform the selection of PROMs used to measure LE in HL. PMID:28592576

A digital wide range neutron flux measuring system for HL-2A

NASA Astrophysics Data System (ADS)

Yuan, Chen; Wu, Jun; Yin, Zejie

2017-08-01

To achieve wide-range, high-integration, and real-time performance on the neutron flux measurement on the HL-2A tokamak, a digital neutron flux measuring (DNFM) system based on the peripheral component interconnection (PCI) eXtension for Instrumentation express (PXIe) bus was designed. This system comprises a charge-sensitive preamplifier and a field programmable gate array (FPGA)-based main electronics plug-in. The DNFM totally covers source-range and intermediate-range neutron flux measurements, and increases system integration by a large margin through joining the pulse-counting mode and Campbell mode. Meanwhile, the neutron flux estimation method based on pulse piling proportions is able to choose and switch measuring modes in accordance with current flux, and this ensures the accuracy of measurements when the neutron flux changes suddenly. It has been demonstrated by simulated signals that the DNFM enhances the full-scale measuring range up to 1.9 × 108 cm-2 s-1, with relative error below 6.1%. The DNFM has been verified to provide a high temporal sensitivity at 10 ms time intervals on a single fission chamber on HL-2A. Contributed paper, published as part of the Proceedings of the 3rd Domestic Electromagnetic Plasma Diagnostics Workshop, September 2016, Hefei, China.

Reading comprehension of health checkup reports and health literacy in Japanese people.

PubMed

Suka, Machi; Odajima, Takeshi; Okamoto, Masako; Sumitani, Masahiko; Nakayama, Takeo; Sugimori, Hiroki

2014-07-01

To determine the reading comprehension of health checkup reports in the context of health literacy (HL) in Japanese people. A web-based survey was conducted among 424 Japanese adults aged 35-59 years. Participants were asked to read specifically designed health checkup reports and then answer a series of questions to examine whether they accomplished the fundamental purposes of health checkup reports (recognition of the problems, recognition of the risk of illness, recognition of the need for preventive action, and motivation for preventive action). HL was simultaneously measured using the 14-item health literacy scale (HLS-14), the 11-item Lipkus scale (Lipkus-J), and the Newest Vital Sign (NVS-J). About 70 % of the study subjects misread the normal/abnormal classification for at least one items. Those with lower HLS-14 scores were significantly less likely to recognize the problems, the risk of illness, and the need for preventive action for the examinee, and also less likely to express their willingness to take preventive action in compliance with the doctor's advice after having received the health checkup report. Compared with the HLS-14 scores, the Lipkus-J and NVS-J scores showed hardly any association with the reading comprehension of health checkup reports. All examinees do not always have an adequate level of HL. HL may be the major determinant of reading comprehension of health checkup reports. For more effective health checkups, health promotion service providers should become aware of the existence of examinees with inadequate HL and address the problem of misreading health checkup results.

HL-10 first flight landing

NASA Technical Reports Server (NTRS)

1966-01-01

The HL-10 Lifting Body completes its first research flight with a landing on Rogers Dry Lake. Due to control problems, pilot Bruce Peterson had to land at a higher speed than originally planned in order to keep the vehicle under control. The actual touchdown speed was about 280 knots. This was 30 knots above the speed called for in the flight plan. The HL-10's first flight had lasted 3 minutes and 9 seconds. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

HL-10 landing on lakebed with F-104 chase aircraft

NASA Technical Reports Server (NTRS)

1970-01-01

In this photo, the HL-10 has touched down on its main landing gear, while the pilot was holding the nose up to slow the vehicle. The F-104 in the background was used as a chase plane. Its pilot would give the HL-10's pilot calls on his altitude above the lakebed as well as warnings about any problems. The NASA F-104s were also used for lifting-body training. With the landing gear extended and flaps lowered, the F-104 could simulate the steep, high-speed descent and landing of a lifting body. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

In vitro synergism of magnolol and honokiol in combination with antibacterial agents against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Zuo, Guo-Ying; Zhang, Xin-Juan; Han, Jun; Li, Yu-Qing; Wang, Gen-Chun

2015-12-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen posing a serious therapeutic challenge in the clinic. It is often multidrug-resistant (MDR) to conventional classes of antibacterial agents and there is an urgent need to develop new agents or strategies for treatment. Magnolol (ML) and honokiol (HL) are two naturally occurring diallylbiphenols which have been reported to show inhibition of MRSA. In this study their synergistic effects with antibacterial agents were further evaluated via checkerboard and time-kill assays. The susceptibility spectrum of clinical MRSA strains was tested by the disk diffusion method. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of ML and HL were assayed by broth microdilution. The synergy was evaluated through checkerboard microdilution and time-killing experiments. ML and HL showed similar activity against both MSSA and MRSA with MIC/MBC at 16 ~ 64 mg/L, with potency similar to amikacin (AMK) and gentamicin (GEN). When they were used in combination with conventional antibacterial agents, they showed bacteriostatic synergy with FICIs between 0.25 ~ 0.5, leading to the combined MICs decreasing to as low as 1 ~ 2 and 1 ~ 16 mg/L for ML (HL) and the agents, respectively. MIC50 of the combinations decreased from 16 mg/L to 1 ~ 4 mg/L for ML (HL) and 8 ~ 128 mg/L to 2 ~ 64 mg/L for the antibacterial agents, which exhibited a broad spectrum of synergistic action with aminoglycosides (AMK, etilmicin (ETM) and GEN), floroquinolones (levofloxacin (LEV), ciprofloxacin and norfloxacin), fosfomycin (FOS) and piperacillin. The times of dilution (TOD, the extent of decreasing in MIC value) were determined up to 16 for the combined MIC. A more significant synergy after combining was determined as ML (HL) with AMK, ETM, GEN and FOS. ML (HL) combined with antibacterial agents did not show antagonistic effects on any of the ten MRSA strains. Reversal effects of MRSA resistance to AMK and GEN by ML and HL were also observed, respectively. All the combinations also showed better dynamic bactericidal activity against MRSA than any of single ML (HL) or the agents at 24 h incubation. The more significant synergy of combinations were determined as HL (ML) + ETM, HL + LEV and HL + AMK (GEN or FOS), with △LC24 of 2.02 ~ 2.25. ML and HL showed synergistic potentiation of antibacterial agents against clinical isolates of MRSA and warrant further pharmacological investigation.

Inhibition of HBV Replication in HepG2.2.15 Cells by Human Peripheral Blood Mononuclear Cell-Derived Dendritic Cells.

PubMed

Liu, Tao; Song, Hong-Li; Zheng, Wei-Ping; Shen, Zhong-Yang

2015-01-01

Anti-HBV therapy is essential for patients awaiting liver transplantation. This study aimed to explore the effects of dendritic cells (DCs) derived from the peripheral blood of hepatitis B patients on the replication of HBV in vivo and to evaluate the biosafety of DCs in clinical therapy. Peripheral blood mononuclear cells (PBMCs) were isolated from HBV-infected patients and maturation-promoting factors and both HBsAg and HBcAg were used to induce DC maturation. Mature DCs and lymphocytes were co-cultured with human hepatocyte cell HL-7702 or HBV-producing human hepatocellular carcinoma cell HepG2.2.15. We found that mature lymphocytes exposed to DCs in vitro did not influence morphology or activities of HL-7702 and HepG2.2.15 cells. Liver function indexes and endotoxin levels in the cell supernatants did not change in these co-cultures. Additionally, supernatant and intracellular HBV DNA levels were reduced when HepG2.2.15 cells were co-cultured with mature lymphocytes that had been cultured with DCs, and HBV covalently closed circular DNA (cccDNA) levels in HepG2.2.15 cells also decreased. Importantly, DC-mediated immunotherapy had no mutagenic effect on HBV genomic DNA by gene sequencing of the P, S, X, and C regions of HBV genomic DNA. We conclude that PBMC-derived DCs from HBV-infected patients act on autologous lymphocytes to suppress HBV replication and these DC clusters showed favorable biosafety. © 2015 by the Association of Clinical Scientists, Inc.

Incidence and relative risk of hearing disorders in professional musicians

PubMed Central

Schink, Tania; Kreutz, Gunter; Busch, Veronika; Pigeot, Iris; Ahrens, Wolfgang

2014-01-01

Background Hearing disorders have been associated with occupational exposure to music. Musicians may benefit from non-amplified and low-intensity music, but may also have high risks of music-induced hearing loss. Aims To compare the incidence of hearing loss (HL) and its subentities in professional musicians with that in the general population. Methods We performed a historical cohort study among insurants between 19 and 66 years who were employed subject to social insurance contributions. The study was conducted with data from three German statutory health insurance providers covering the years 2004–2008 with about 7 million insurants. Incidence rates with 95% CIs of HL and the subentities noise-induced hearing loss (NIHL), conductive HL, sensorineural HL, conductive and sensorineural HL, as well as tinnitus were estimated stratified by age, sex and federal state. A Cox regression analysis was conducted to estimate adjusted HRs and two-sided 95% CIs for HL and its subentities. Results More than 3 million insurants were eligible, of whom 2227 were identified as professional musicians (0.07%). During the 4-year observation period, 283 697cases of HL were seen, 238 of them among professional musicians (0.08%), leading to an unadjusted incidence rate ratio of 1.27. The adjusted hazard ratio of musicians was 1.45 (95% CI 1.28 to 1.65) for HL and 3.61 (95% CI 1.81 to 7.20) for NIHL. Conclusions Professional musicians have a high risk of contracting hearing disorders. Use of already available prevention measures should reduce the incidence of HL in professional musicians. PMID:24790053

Melatonin induction and its role in high light stress tolerance in Arabidopsis thaliana.

PubMed

Lee, Hyoung Yool; Back, Kyoungwhan

2018-05-16

In plants, melatonin is a potent bioactive molecule involved in the response against various biotic and abiotic stresses. However, little is known of its defensive role against high light (HL) stress. In this study, we found that melatonin was transiently induced in response to HL stress in Arabidopsis thaliana with a simultaneous increase in the expression of melatonin biosynthetic genes, including serotonin N-acetyltransferase1 (SNAT1). Transient induction of melatonin was also observed in the flu mutant, a singlet oxygen ( 1 O 2 )-producing mutant, upon light exposure, suggestive of melatonin induction by chloroplastidic 1 O 2 against HL stress. An Arabidopsis snat1 mutant was devoid of melatonin induction upon HL stress, resulting in high susceptibility to HL stress. Exogenous melatonin treatment mitigated damage caused by HL stress in the snat1 mutant by reducing O 2 - production and increasing the expression of various ROS-responsive genes. In analogy, an Arabidopsis SNAT1-overexpressing line showed increased tolerance of HL stress concomitant with a reduction in malondialdehyde and ion leakage. A complementation line expressing an Arabidopsis SNAT1 genomic fragment in the snat1 mutant completely restored HL stress susceptibility in the snat1 mutant to levels comparable to that of wild-type Col-0 plants. The results of the analysis of several Arabidopsis genetic lines reveal for the first time at the genetic level that melatonin is involved in conferring HL stress tolerance in plants. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

HL-10 flight simulator

NASA Technical Reports Server (NTRS)

1968-01-01

As shown in this photo of the HL-10 flight simulator, the lifting-body pilots and engineers made use of early simulators for both training and the determination of a given vehicle's handling at various speeds, attitudes, and altitudes. This provided warning of possible problems. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

HL-10 on lakebed with B-52 flyby

NASA Technical Reports Server (NTRS)

1969-01-01

NASA research pilot Bill Dana takes a moment to watch NASA's NB-52B cruise overhead after a research flight in the HL-10. On the left, John Reeves can be seen at the cockpit of the lifting body. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Responses of the picoprasinophyte Micromonas commoda to light and ultraviolet stress.

PubMed

Cuvelier, Marie L; Guo, Jian; Ortiz, Alejandra C; van Baren, Marijke J; Tariq, Muhammad Akram; Partensky, Frédéric; Worden, Alexandra Z

2017-01-01

Micromonas is a unicellular marine green alga that thrives from tropical to polar ecosystems. We investigated the growth and cellular characteristics of acclimated mid-exponential phase Micromonas commoda RCC299 over multiple light levels and over the diel cycle (14:10 hour light:dark). We also exposed the light:dark acclimated M. commoda to experimental shifts from moderate to high light (HL), and to HL plus ultraviolet radiation (HL+UV), 4.5 hours into the light period. Cellular responses of this prasinophyte were quantified by flow cytometry and changes in gene expression by qPCR and RNA-seq. While proxies for chlorophyll a content and cell size exhibited similar diel variations in HL and controls, with progressive increases during day and decreases at night, both parameters sharply decreased after the HL+UV shift. Two distinct transcriptional responses were observed among chloroplast genes in the light shift experiments: i) expression of transcription and translation-related genes decreased over the time course, and this transition occurred earlier in treatments than controls; ii) expression of several photosystem I and II genes increased in HL relative to controls, as did the growth rate within the same diel period. However, expression of these genes decreased in HL+UV, likely as a photoprotective mechanism. RNA-seq also revealed two genes in the chloroplast genome, ycf2-like and ycf1-like, that had not previously been reported. The latter encodes the second largest chloroplast protein in Micromonas and has weak homology to plant Ycf1, an essential component of the plant protein translocon. Analysis of several nuclear genes showed that the expression of LHCSR2, which is involved in non-photochemical quenching, and five light-harvesting-like genes, increased 30 to >50-fold in HL+UV, but was largely unchanged in HL and controls. Under HL alone, a gene encoding a novel nitrite reductase fusion protein (NIRFU) increased, possibly reflecting enhanced N-assimilation under the 625 μmol photons m-2 s-1 supplied in the HL treatment. NIRFU's domain structure suggests it may have more efficient electron transfer than plant NIR proteins. Our analyses indicate that Micromonas can readily respond to abrupt environmental changes, such that strong photoinhibition was provoked by combined exposure to HL and UV, but a ca. 6-fold increase in light was stimulatory.

Responses of the picoprasinophyte Micromonas commoda to light and ultraviolet stress

DOE PAGES

Cuvelier, Marie L.; Guo, Jian; Ortiz, Alejandra C.; ...

2017-03-09

Micromonas is a unicellular marine green alga that thrives from tropical to polar ecosystems. We investigated the growth and cellular characteristics of acclimated mid-exponential phase Micromonas commoda RCC299 over multiple light levels and over the diel cycle (14:10 hour light:dark). We also exposed the light:dark acclimated M. commoda to experimental shifts from moderate to high light (HL), and to HL plus ultraviolet radiation (HL+UV), 4.5 hours into the light period. Cellular responses of this prasinophyte were quantified by flow cytometry and changes in gene expression by qPCR and RNA-seq. While proxies for chlorophyll a content and cell size exhibited similarmore » diel variations in HL and controls, with progressive increases during day and decreases at night, both parameters sharply decreased after the HL+UV shift. Two distinct transcriptional responses were observed among chloroplast genes in the light shift experiments: i) expression of transcription and translation-related genes decreased over the time course, and this transition occurred earlier in treatments than controls; ii) expression of several photosystem I and II genes increased in HL relative to controls, as did the growth rate within the same diel period. However, expression of these genes decreased in HL+UV, likely as a photoprotective mechanism. RNA-seq also revealed two genes in the chloroplast genome, ycf2-like and ycf1-like, that had not previously been reported. The latter encodes the second largest chloroplast protein in Micromonas and has weak homology to plant Ycf1, an essential component of the plant protein translocon. Analysis of several nuclear genes showed that the expression of LHCSR2, which is involved in non-photochemical quenching, and five light-harvesting-like genes, increased 30 to >50-fold in HL+UV, but was largely unchanged in HL and controls. Under HL alone, a gene encoding a novel nitrite reductase fusion protein (NIRFU) increased, possibly reflecting enhanced N-assimilation under the 625 μmol photons m -2 s -1 supplied in the HL treatment. NIRFU's domain structure suggests it may have more efficient electron transfer than plant NIR proteins. Lastly, our analyses indicate that Micromonas can readily respond to abrupt environmental changes, such that strong photoinhibition was provoked by combined exposure to HL and UV, but a ca. 6-fold increase in light was stimulatory.« less

HL-10 on lakebed with Jerauld R. Gentry, Peter Hoag, John A. Manke, and Bill Dana

NASA Technical Reports Server (NTRS)

1969-01-01

The four principal HL-10 pilots are seen here with the lifting body aircraft. They are, left to right; Air Force Major Jerauld R. Gentry, Air Force test pilot Peter Hoag, and NASA pilots John A. Manke and Bill Dana. All are wearing the pressure suits needed for flying above 50,000 feet. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

HL-10 after first flight with pilot Bruce Peterson

NASA Technical Reports Server (NTRS)

1966-01-01

The HL-10 after its first flight, shown with pilot Bruce Peterson. Although the lifting-body aircraft was predicted to have good flying qualities, this first flight showed major control and stability problems. The cause was airflow separation from the vehicle's fins. Changes to the fins' leading-edge shape fixed the problem. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

HL-10 on lakebed with pilot John Manke

NASA Technical Reports Server (NTRS)

1969-01-01

John Manke is shown here on the lakebed next to the HL-10, one of four different lifting-body vehicles he flew, including the X-24B, which he flew 16 times. His total of 42 lifting-body flights was second only to the 51 flights Milt Thompson achieved, including one in the remotely piloted Hyper III. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Responses of the picoprasinophyte Micromonas commoda to light and ultraviolet stress

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

Cuvelier, Marie L.; Guo, Jian; Ortiz, Alejandra C.

Micromonas is a unicellular marine green alga that thrives from tropical to polar ecosystems. We investigated the growth and cellular characteristics of acclimated mid-exponential phase Micromonas commoda RCC299 over multiple light levels and over the diel cycle (14:10 hour light:dark). We also exposed the light:dark acclimated M. commoda to experimental shifts from moderate to high light (HL), and to HL plus ultraviolet radiation (HL+UV), 4.5 hours into the light period. Cellular responses of this prasinophyte were quantified by flow cytometry and changes in gene expression by qPCR and RNA-seq. While proxies for chlorophyll a content and cell size exhibited similarmore » diel variations in HL and controls, with progressive increases during day and decreases at night, both parameters sharply decreased after the HL+UV shift. Two distinct transcriptional responses were observed among chloroplast genes in the light shift experiments: i) expression of transcription and translation-related genes decreased over the time course, and this transition occurred earlier in treatments than controls; ii) expression of several photosystem I and II genes increased in HL relative to controls, as did the growth rate within the same diel period. However, expression of these genes decreased in HL+UV, likely as a photoprotective mechanism. RNA-seq also revealed two genes in the chloroplast genome, ycf2-like and ycf1-like, that had not previously been reported. The latter encodes the second largest chloroplast protein in Micromonas and has weak homology to plant Ycf1, an essential component of the plant protein translocon. Analysis of several nuclear genes showed that the expression of LHCSR2, which is involved in non-photochemical quenching, and five light-harvesting-like genes, increased 30 to >50-fold in HL+UV, but was largely unchanged in HL and controls. Under HL alone, a gene encoding a novel nitrite reductase fusion protein (NIRFU) increased, possibly reflecting enhanced N-assimilation under the 625 μmol photons m -2 s -1 supplied in the HL treatment. NIRFU's domain structure suggests it may have more efficient electron transfer than plant NIR proteins. Lastly, our analyses indicate that Micromonas can readily respond to abrupt environmental changes, such that strong photoinhibition was provoked by combined exposure to HL and UV, but a ca. 6-fold increase in light was stimulatory.« less

Glyceryl monooleyl ether-based liquid crystalline nanoparticles as a transdermal delivery system of flurbiprofen: characterization and in vitro transport.

PubMed

Uchino, Tomonobu; Murata, Akiko; Miyazaki, Yasunori; Oka, Toshihiko; Kagawa, Yoshiyuki

2015-01-01

Liquid crystalline nanoparticles (LCNs) were prepared using glyceryl monooleyl ether (GME) by the modified film rehydration method. Hydrogenated lecithin (HL), 1,3-butylene glycol (1,3-BG), and Poloxamer 407 were used as additives. The prepared LCN formulations were evaluated based on particle size, small-angle X-ray diffraction (SAXS) analysis, (1)H- and (19)F-NMR spectra, and in vitro skin permeation across Yucatan micropig skin. The composition (weight percent) of the LCN formulations were GME-HL-1,3-BG (4 : 1 : 15), 4% GME-based LCN and GME-HL-1,3-BG (8 : 1 : 15), 8% GME-based LCN and their mean particle sizes were 130-175 nm. Flurbiprofen 5 and 10 mg was loaded into 4% GME-based LCN and 8% GME-based LCN systems, respectively. The results of SAXS and NMR suggested that both flurbiprofen-loaded formulations consist of particles with reverse type hexagonal phase (formation of hexosome) and flurbiprofen molecules were localized in the lipid domain through interaction of flurbiprofen with the lipid components. Flurbiprofen transport from the LCN systems across the Yucatan micropig skin was increased compared to flurbiprofen in citric buffer (pH=3.0). The 8% GME-based LCN systems was superior to the 4% GME-based LCN for flurbiprofen transport. Since the internal hexagonal phase in the 8% GME-based LCN systems had a higher degree of order compared to the 4% GME-based LCN in SAXS patterns, the 8% GME-based LCN system had a larger surface area, which might influence flurbiprofen permeation. These results indicated that the GME-based LCN system is effective in improving the skin permeation of flurbiprofen across the skin.

The induction of monocytopoiesis in HL-60 promyelocytic leukemia cells is inhibited by hydroquinone, a toxic metabolite of benzene

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

Oliveira, N.L.

1992-01-01

Chronic exposure of humans to benzene has been shown to have a cytotoxic effect on hematopoietic progenitor cells in intermediate stages of differentiation which can lead to aplastic anemia and acute myelogenous leukemia. This thesis examined the effect of hydroquinone, a toxic metabolite of benzene found in the bone marrow, on the human promyelocytic leukemia cell line (HL-60) which can be induced to differentiate to both monocyte and myeloid cells, and thus has been used as a surrogate for a granulocyte/macrophage progenitor cell. Exposure of HL-60 cells to noncytotoxic concentrations of hydroquinone for three hours prior to induction with 12-O-tetradecanoylmore » phorbol-13-acetate caused a dose-dependent inhibition of the acquisition of characteristics of monocytic differentiation. These included adherence, nonspecific esterase activity and phagocytosis. Hydroquinone had no effect on cell proliferation. Hydroquinone appeared to be affecting maturation beyond the monoblast/promonocyte stages. Hydroquinone also prevented differentiation induced by 1, 25-dihydroxy vitamin D[sub 3], however, the block occurred after the acquisition of adherence. Hydroquinone at concentrations that inhibited monocytic differentiation had no effect on differentiation to granulocytes, suggesting that the block in the differentiation of these bipotential cells is at a step unique to the monocytic pathway. Hydroquinone was unable to prevent differentiation induced by the macrophage-derived cytokine interleukin-1, a differentiation factor for cells of the monocytic lineage. These data demonstrate that treatment of Hl-60 cells with hydroquinone prior to induction of differentiation prevents the acquisition of the monocytic phenotype induced by TPA or 1, 25(OH)[sub 2]D[sub 3] by a mechanism which at present is unknown, but which appears to be specific for the monocytic pathway. These results are of considerable significance for benzene hematotoxicity.« less

Induction of non-apoptotic cell death by morphinone in human promyelocytic leukemia HL-60 cells.

PubMed

Takeuchi, Risa; Hoshijima, Hiroshi; Nagasaka, Hiroshi; Chowdhury, Shahead Ali; Kikuchi, Hirotaka; Kanda, Yumiko; Kunii, Shiro; Kawase, Masami; Sakagami, Hiroshi

2006-01-01

As previously suggested, codeinone (oxidation product of codeine) induces non-apoptotic cell death, characterized by marginal caspase activation and the lack of DNA fragmentation in HL-60 human promyelocytic leukemia cells, which was inhibited by N-acetyl-L-cysteine. Whether, morphinone, an oxidative metabolite of morphine, also induced a similar type of cell death in HL-60 cells was investigated. Morphinone showed slightly higher cytotoxic activity against human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, HSC-4, NA, Ca9-22, promyelocytic leukemia HL-60, cervical carcinoma HeLa) than against normal oral human cells (gingival fibroblast HGF, pulp cells HPC, periodontal ligament fibroblast HPLF). Morphinone also induced an almost undetectable level of internucleosomal DNA fragmentation in the HL-60 cells. Morphinone did not activate caspase-8 or -9 in these cells. Morphinone dose-dependently activated caspase-3 in both HL-60 and HSC-2 cell lines, but to a much lesser extent than actinomycin D. Electron microscopy demonstrated that morphinone induced mitochondrial shrinkage, vacuolization and production of autophagosome and the loss of cell surface microvilli, without destruction of cell surface and nuclear membranes in the HL-60 cells. The autophagy inhibitor 3-methyladenine (0.3-10 mM) slightly inhibited the morphinone-induced cytotoxicity, when corrected for its own cytotoxicity. These data suggest that morphinone induces non-apoptotic cell death in HL-60 cells.

Does acculturation narrow the health literacy gap between immigrants and non-immigrants-An explorative study.

PubMed

Mantwill, Sarah; Schulz, Peter J

2017-04-01

To compare functional health literacy (HL) levels in three immigrant groups to those of the German- and Italian-speaking non-immigrant population in Switzerland. Moreover, to investigate whether language-independent, respectively language-dependent, functional HL and variables of acculturation were associated with self-reported health status among immigrants. Language-independent HL was assessed with the Short Test of Functional Health Literacy (S-TOFHLA) in the respective native languages. Language-dependent HL was measured using Brief Health Literacy Screeners (BHLS) asking about participants' confidence in understanding medical information in the language of the host country. Measures of acculturation included length of stay and age when taking residency in Switzerland. In particular Albanian- and Portuguese-speaking immigrants had lower levels of functional HL. In unadjusted analysis "age when taking residency in Switzerland" was associated with the BHLS. Adjusted analysis showed that the BHLS were significantly associated with self-reported health among all immigrant groups (p≤0.01). Functional HL that is dependent on understanding of medical information in the language of the new host country is a better predictor for self-reported health status among immigrants than language-independent HL. In the clinical setting limited functional HL might be a significant obstacle to successful disease treatment and prevention in immigrants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical Features and Prognostic Factors of Hodgkin's Lymphoma: A Single Center Experience.

PubMed

Kılıçkap, Saadettin; Barışta, Ibrahim; Ulger, Sükran; Celik, Ismail; Selek, Uğur; Yıldız, Ferah; Kars, Ayşe; Ozışık, Yavuz; Tekuzman, Gülten

2013-06-01

Hodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. Retrospective study. Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of "B" symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country.

Role of Visual Speech in Phonological Processing by Children With Hearing Loss

PubMed Central

Jerger, Susan; Tye-Murray, Nancy; Abdi, Hervé

2011-01-01

Purpose This research assessed the influence of visual speech on phonological processing by children with hearing loss (HL). Method Children with HL and children with normal hearing (NH) named pictures while attempting to ignore auditory or audiovisual speech distractors whose onsets relative to the pictures were either congruent, conflicting in place of articulation, or conflicting in voicing—for example, the picture “pizza” coupled with the distractors “peach,” “teacher,” or “beast,” respectively. Speed of picture naming was measured. Results The conflicting conditions slowed naming, and phonological processing by children with HL displayed the age-related shift in sensitivity to visual speech seen in children with NH, although with developmental delay. Younger children with HL exhibited a disproportionately large influence of visual speech and a negligible influence of auditory speech, whereas older children with HL showed a robust influence of auditory speech with no benefit to performance from adding visual speech. The congruent conditions did not speed naming in children with HL, nor did the addition of visual speech influence performance. Unexpectedly, the /∧/-vowel congruent distractors slowed naming in children with HL and decreased articulatory proficiency. Conclusions Results for the conflicting conditions are consistent with the hypothesis that speech representations in children with HL (a) are initially disproportionally structured in terms of visual speech and (b) become better specified with age in terms of auditorily encoded information. PMID:19339701

Hodgkin Lymphoma has a seasonal pattern of incidence and mortality that depends on latitude.

PubMed

Borchmann, Sven; Müller, Horst; Engert, Andreas

2017-11-02

Seasonal variations in incidence and mortality after a Hodgkin lymphoma (HL) diagnosis have been previously described with partly conflicting results. The goal of this analysis is to provide a comprehensive analysis of these seasonal variations. In total, 41,405 HL cases diagnosed between 1973 and 2012 in the 18 Surveillance, Epidemiology, and End Results registries were included. Cosinor analysis and Cox proportional-hazards models were employed to analyze seasonality of incidence and mortality, respectively. HL shows a sinusoid seasonal incidence pattern (p < 0.001). Estimated incidence in March is 15.4% [95%-CI: 10.8-20.0] higher than in September. This sinusoid pattern is more pronounced at higher latitudes (p = 0.023). The risk of dying within the first three years after a HL diagnosis in winter is significantly increased compared to a HL diagnosis in summer at higher latitudes (HR = 1.082 [95%-CI: 1.009-1.161], p = 0.027). Furthermore, increasing northern latitude increases the additional mortality risk conferred by a diagnosis in winter (p interaction 0.033). The seasonality patterns presented here provide epidemiological evidence that Vitamin D might play a protective role in HL. Further evidence on the direct association between Vitamin D levels and the clinical course of HL needs to be collected to advance the understanding of the role of Vitamin D in HL.

Early/Late Heterobimetallic Tantalum/Rhodium Species Assembled Through a Novel Bifunctional NHC-OH Ligand.

PubMed

Srivastava, Ravi; Moneuse, Raphaël; Petit, Julien; Pavard, Paul-Alexis; Dardun, Vincent; Rivat, Madleen; Schiltz, Pauline; Solari, Marius; Jeanneau, Erwann; Veyre, Laurent; Thieuleux, Chloé; Quadrelli, Elsje Alessandra; Camp, Clément

2018-03-20

The straightforward synthesis of a new unsymmetrical hydroxy-tethered N-heterocyclic carbene (NHC) ligand, HL, is presented. The free ligand exhibits an unusual OH-carbene hydrogen-bonding interaction. This OH-carbene motif was used to yield 1) the first tantalum complex displaying both a Fischer- and Schrock-type carbene ligand and 2) a unique NHC-based early/late heterobimetallic complex. More specifically, the protonolysis chemistry between the ligand's hydroxy group and imido-alkyl or alkylidene-alkyl tantalum precursor complexes yielded the rare monometallic tantalum-NHC complexes [Ta(XtBu)(L)(CH 2 tBu) 2 ] (X=N, CH), in which the alkoxy-carbene ligand acts as a chelate. In contrast, HL only binds to rhodium through the NHC unit in [Rh(HL)(cod)Cl] (cod=cycloocta-1,5-diene), the hydroxy pendant arm remaining unbound. This bifunctional ligand scaffold successfully promoted the assembly of rhodium/tantalum heterobimetallic complexes upon either 1) the insertion of [Rh(cod)Cl] 2 into the Ta-NHC bond in [Ta(NtBu)(L)(CH 2 tBu) 2 ] or 2) protonolysis between the free hydroxy group in [Rh(HL)(cod)Cl] and one alkyl group in [Ta(NtBu)(CH 2 tBu) 3 ]. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Syntheses, crystal structures, and properties of four complexes based on polycarboxylate and imidazole ligands

NASA Astrophysics Data System (ADS)

Qiao, Rui; Chen, Shui-Sheng; Sheng, Liang-Quan; Yang, Song; Li, Wei-Dong

2015-08-01

Four metal-organic coordination polymers [Zn(HL)(H2O)]·4H2O (1), [Zn(HL)(L1)]·4H2O (2), [Cu(HL)(H2O)]·3H2O (3) and [Cu(HL)(L1)]·5H2O (4) were synthesized by reactions of the corresponding metal(II) salts with semirigid polycarboxylate ligand (5-((4-carboxypiperidin-1-yl)methyl)isophthalic acid hydrochloride, H3L·HCl) or auxiliary ligand (1,4-di(1H-imidazol-4-yl)benzene, L1). The structures of the compounds were characterized by elemental analysis, FT-IR spectroscopy and single-crystal X-ray diffraction. The use of auxiliary ligand L1 has great influence on the structures of two pairs of complexes 1, 2 and 3, 4. Complex 1 is a uninodal 3-connected rare 2-fold interpenetrating ZnSc net with a Point (Schlafli) symbol of (103) while 2 is a one-dimensional (1D) ladder structure. Compound 3 features a two-dimensional (2D) honeycomb network with typical 63-hcb topology, while 4 is 2D network with (4, 4) sql topology based on binuclear CuII subunits. The non-covalent bonding interactions such as hydrogen bonds, π···π stacking and C-H···π exist in complexes 1-4, which contributes to stabilize crystal structure and extend the low-dimensional entities into high-dimensional frameworks. And the photoluminescent property of 1 and 2 and gas sorption property of 4 have been investigated.

Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity.

PubMed

Leite, Elaine A; Souza, Cristina M; Carvalho-Júnior, Alvaro D; Coelho, Luiz G V; Lana, Angela M Q; Cassali, Geovanni D; Oliveira, Mônica C

2012-01-01

Cisplatin (CDDP) is one of the most effective and potent anticancer drugs used as first-line chemotherapy against several solid tumors. However, the severe side effects and its tendency to provoke chemoresistance often limit CDDP therapy. To avoid these inconveniences, the present study's research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP). The present study aimed to evaluate the antitumor effect and toxicity of SpHL-CDDP, as compared with that of free CDDP, and long-circulating and non- pH-sensitive liposomes containing CDDP (NSpHL-CDDP), after their intravenous administration in solid Ehrlich tumor-bearing mice. Antitumor activity was evaluated by analysis of tumor volume and growth inhibition ratio, serum vascular endothelial growth factor (VEGF) levels, and histomorphometric and immunohistochemical studies. Body weight variation and the histological examination of bone marrow and kidneys were used as toxicity indicators. A significant reduction in the tumor volume and a higher tumor growth inhibition ratio was observed after SpHL-CDDP treatment, compared with free CDDP and NSpHL-CDDP treatments. In addition, complete remission of the tumor was detected in 18.2% of the mice treated with SpHL- CDDP (16 mg/kg). As such, the administration of SpHL-CDDP, as compared with free CDDP and NSpHL-CDDP, led to a decrease in the area of necrosis and in the percentage of positive CDC 47 tumor cells. A significant reduction in the VEGF serum level was also observed after SpHL-CDDP treatment, as compared with free-CDDP treatment. SpHL-CDDP administered in a two-fold higher dose than that of free CDDP presented a loss in body weight and changes in the hematopoietic tissue morphology, which proved to be similar to that of free CDDP. No changes could be verified in the renal tissue after any formulations containing CDDP had been administered. These findings showed that SpHL-CDDP allowed for the administration of higher doses of CDDP, significantly improving its antitumor effect.

Development of Hospital-based Data Sets as a Vehicle for Implementation of a National Electronic Health Record

PubMed Central

Keikha, Leila; Farajollah, Seyede Sedigheh Seied; Safdari, Reza; Ghazisaeedi, Marjan; Mohammadzadeh, Niloofar

2018-01-01

Background In developing countries such as Iran, international standards offer good sources to survey and use for appropriate planning in the domain of electronic health records (EHRs). Therefore, in this study, HL7 and ASTM standards were considered as the main sources from which to extract EHR data. Objective The objective of this study was to propose a hospital data set for a national EHR consisting of data classes and data elements by adjusting data sets extracted from the standards and paper-based records. Method This comparative study was carried out in 2017 by studying the contents of the paper-based records approved by the health ministry in Iran and the international ASTM and HL7 standards in order to extract a minimum hospital data set for a national EHR. Results As a result of studying the standards and paper-based records, a total of 526 data elements in 174 classes were extracted. An examination of the data indicated that the highest number of extracted data came from the free text elements, both in the paper-based records and in the standards related to the administrative data. The major sources of data extracted from ASTM and HL7 were the E1384 and Hl7V.x standards, respectively. In the paper-based records, data were extracted from 19 forms sporadically. Discussion By declaring the confidentiality of information, the ASTM standards acknowledge the issue of confidentiality of information as one of the main challenges of EHR development, and propose new types of admission, such as teleconference, tele-video, and home visit, which are inevitable with the advent of new technology for providing healthcare and treating diseases. Data related to finance and insurance, which were scattered in different categories by three organizations, emerged as the financial category. Documenting the role and responsibility of the provider by adding the authenticator/signature data element was deemed essential. Conclusion Not only using well-defined and standardized data, but also adapting EHR systems to the local facilities and the existing social and cultural conditions, will facilitate the development of structured data sets. PMID:29618962

Development of Hospital-based Data Sets as a Vehicle for Implementation of a National Electronic Health Record.

PubMed

Keikha, Leila; Farajollah, Seyede Sedigheh Seied; Safdari, Reza; Ghazisaeedi, Marjan; Mohammadzadeh, Niloofar

2018-01-01

In developing countries such as Iran, international standards offer good sources to survey and use for appropriate planning in the domain of electronic health records (EHRs). Therefore, in this study, HL7 and ASTM standards were considered as the main sources from which to extract EHR data. The objective of this study was to propose a hospital data set for a national EHR consisting of data classes and data elements by adjusting data sets extracted from the standards and paper-based records. This comparative study was carried out in 2017 by studying the contents of the paper-based records approved by the health ministry in Iran and the international ASTM and HL7 standards in order to extract a minimum hospital data set for a national EHR. As a result of studying the standards and paper-based records, a total of 526 data elements in 174 classes were extracted. An examination of the data indicated that the highest number of extracted data came from the free text elements, both in the paper-based records and in the standards related to the administrative data. The major sources of data extracted from ASTM and HL7 were the E1384 and Hl7V.x standards, respectively. In the paper-based records, data were extracted from 19 forms sporadically. By declaring the confidentiality of information, the ASTM standards acknowledge the issue of confidentiality of information as one of the main challenges of EHR development, and propose new types of admission, such as teleconference, tele-video, and home visit, which are inevitable with the advent of new technology for providing healthcare and treating diseases. Data related to finance and insurance, which were scattered in different categories by three organizations, emerged as the financial category. Documenting the role and responsibility of the provider by adding the authenticator/signature data element was deemed essential. Not only using well-defined and standardized data, but also adapting EHR systems to the local facilities and the existing social and cultural conditions, will facilitate the development of structured data sets.

HMG-CoA lyase (HL) gene: Cloning and characterization of the 5{prime} end of the mouse gene, gene targeting in ES cells, and demonstration of large deletions in three HL-deficient patients

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

Wang, S.; Robert, M.F.; Mitchell, G.A.

1994-09-01

3-hydroxy-3-methylglutaryl CoA lyase (HL) is a mitochondrial matrix enzyme which catalyzes the last step of leucine catabolism and of ketogenesis. Autosomal recessive HL deficiency in humans results in episodes of hypoglycemia and coma. We are interested in the pathophysiology of HL deficiency as a model for both amino acid and fatty acid inborn errors. We have cloned the human and mouse HL genes. In order to analyze the 5{prime} nontranslated region of mouse HL gene, we cloned and sequenced a 1.8 kb fragment containing the 5{prime} extremity including exon 1 and about 1.6 kb of 5{prime} nontranslated sequence. The regionmore » surrounding exon 1 is CpG-rich (66.4%). Using the criteria of West, the Observed/Expected ratio for CpG dinucleotides is 0.7 ({ge}0.6 is consistent with a CpG island). We are carrying out primer extension and RNase protection experiments to determine the transcription initiation site. We constructed a gene targeting vector by introducing the neomycin resistance gene into exon 2 of a 7.5 kb genomic subclone of the mouse HL gene. Targeting was performed by electroporating 10 mg linearized vector into 10{sup 7} ES cells and selecting for 12 days with G418. 5/228 colonies (2.2%) had homologous recombination as shown by PCR screening and Southern analysis. We are microinjecting the 5 targeted clones into blastocysts to create an HL-deficient mouse. To date we have obtained two chimeras with contributions of 95% and 55% from 129, by coat color estimates. Three of 27 (11%) of the HL-deficient patients studied were suggested by genomic Southern analysis to be homozygous for large intragenic deletions. We confirmed this and defined the boundaries using exonic PCR.« less

Modulation of transferrin receptor mRNA by transferrin-gallium in human myeloid HL60 and lymphoid CCRF-CEM leukaemic cells.

PubMed Central

Ul-Haq, R; Chitambar, C R

1993-01-01

Gallium binds to the iron transport protein transferrin (Tf), is incorporated into cells through transferrin receptors (TfR) and inhibits iron-dependent DNA synthesis. Since cellular TfR expression is tightly regulated by the availability of iron, we investigated the effects of transferrin-gallium (Tf-Ga) on TfR mRNA levels in myeloid HL60 and lymphoid CCRF-CEM cells. In HL60 cells, Tf-Ga increased TfR mRNA levels in a dose-dependent fashion. This increase in TfR mRNA was blocked by Tf-Fe and by cycloheximide. Analysis of the rate of mRNA decay in the presence of actinomycin D revealed that the half-life of TfR mRNA was increased in HL60 cells incubated with Tf-Ga. The rate of transcription of TfR mRNA was not increased by Tf-Ga. In contrast with HL60 cells, CCRF-CEM cells displayed a decrease in the level of TfR mRNA after incubation with Tf-Ga. Tf-Ga inhibited iron uptake in both HL60 and CCRF-CEM cells but increased the level of TfR mRNA only in HL60 cells, suggesting that the Tf-Ga induction of TfR mRNA was not solely due to inhibition of cellular iron uptake. At growth-inhibitory concentrations, Tf-Ga increased the TfR mRNA level in HL60 cells but decreased it in CCRF-CEM cells. Our studies suggest that in HL60 cells, gallium regulates TfR expression at the post-transcriptional level by mechanisms which require de novo protein synthesis and involve interaction with iron. The divergent effects of Tf-Ga on TfR mRNA in myeloid HL60 and lymphoid CCRF-CEM cells suggest that differences exist in the regulation of TfR expression between these two cell types. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8379943

Synergistic growth inhibition in HL-60 cells by the combination of acyclic retinoid and vitamin K2.

PubMed

Kitagawa, Junichi; Hara, Takeshi; Tsurumi, Hisashi; Ninomiya, Soranobu; Ogawa, Kengo; Adachi, Seiji; Kanemura, Nobuhiro; Kasahara, Senji; Shimizu, Masahito; Moriwaki, Hisataka

2011-05-01

The aim of this study was to assess the effects of acyclic retinoid (ACR) and vitamin K(2) (VK(2)) in HL-60 cells. We used HL-60 cells, and the Trypan Blue dye exclusion method was used for cell proliferation assays. For detection of apoptosis, the Annexin V-binding capacity of treated cells was examined by flow cytometry. To evaluate the cell cycle, we used a FITC BrdU Flow KIT and flow cytometry. Total extracted and equivalent amounts of protein were examined by Western blotting using specific antibodies. ACR and VK(2) dose dependently inhibited the proliferation of HL-60 cells. These two agents in combination synergistically inhibited cell growth and induced apoptosis. VK(2) inhibited activation of the Ras/MAPK signaling pathway, and ACR plus VK(2) cooperatively inhibited phosphorylation of RXRα and the growth of HL-60 cells. Moreover, ACR and VK(2) induced increases in G0/G1 phase HL-60 cells, alone and synergistically in combination. The synergistic effects of ACR and VK(2) on HL-60 cells may provide a novel strategy for treating leukemia.

Cuphiin D1, the macrocyclic hydrolyzable tannin induced apoptosis in HL-60 cell line.

PubMed

Wang, C C; Chen, L G; Yang, L L

2000-02-28

Cuphiin D1 (CD1), a new macrocyclic hydrolyzable tannin isolated from Cuphea hyssopifolia, has been shown to exert antitumor activity both in vitro and in vivo. In this study, we explored the mechanism of the CD1-induced antitumor effect on human promyelocytic leukemia (HL-60) cells. The results showed that CD1 induced cytotoxicity in HL-60 cells and the IC50 was 16 microM after 36 h treatment. HL-60 cells treated with CD1 for 36 h decreased the uptake of [3H]-labeled thymidine, uridine and leucine in a dose dependent manner. Electron micrographs demonstrated that HL-60 cells treated with 16 microM CD1 for 36 h exhibited chromatin condensation, indicating the apoptosis occurrence. Flow cytometric analysis demonstrated the presence of apoptotic cells with low DNA content, a decrease of cell population at G2/M phase, and a concomitant increase of cell population at G1 phase. CD1 also caused DNA fragmentation and inhibited Bcl-2 expression in the HL-60 cells. These results suggest that the inhibition of Bcl-2 expression in HL-60 cell might account for the mechanism of CD1-induced apoptosis.

A Meta-Analysis of Hodgkin Lymphoma Reveals 19p13.3 TCF3 as a Novel Susceptibility Locus

PubMed Central

Cozen, W; Timofeeva, MN; Li, D; Diepstra, A; Hazelett, D; Delahaye-Sourdeix, M; Edlund, CK; Franke, L; Rostgaard, K; Van Den Berg, DJ; Cortessis, VK; Smedby, KE; Glaser, SL; H-J, Westra; Robison, LL; Mack, TM; Ghesquieres, H; Hwang, AE; Nieters, A; de Sanjose, S; Lightfoot, T; Becker, N; Maynadie, M; Foretova, L; Roman, E; Benavente, Y; Rand, KA; Nathwani, BN; Glimelius, B; Staines, A; Boffetta, P; Link, BK; Kiemeney, L; Ansell, SM; Bhatia, S; Strong, LC; Galan, P; Vatten, L; Habermann, TM; Duell, EJ; Lake, A; Veenstra, RN; Visser, L; Liu, Y; Urayama, KY; Montgomery, D; Gaborieau, V; Weiss, LM; Byrnes, G; Lathrop, M; Cocco, P; Best, T; Skol, AD; H-O, Adami; Melbye, M; Cerhan, JR; Gallagher, A; Taylor, GM; Slager, SL; Brennan, P; Coetzee, GA; Conti, DV; Onel, K; Jarrett, RF; Hjalgrim, H; van den Berg, A; McKay, JD

2014-01-01

Recent genome wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio [OR] = 0.81, 95% confidence interval [95% CI] = 0.76–0.86, Pcombined = 3.5 × 10−10), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16.1, 5q31, 6p31.2, 8q24.21 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk PMID:24920014

Synergism between NF-kappa B inhibitor, celastrol, and XIAP inhibitor, embelin, in an acute myeloid leukemia cell line, HL-60.

PubMed

Pazhang, Yaghub; Jaliani, Hossein Zarei; Imani, Mehdi; Dariushnejad, Hassan

2016-01-01

Embelin and celastrol, inhibitors of XIAP and NF-κB proteins respectively, have been derived from natural sources and shown anti-tumor activities against different cancer cell lines. Some interactions have recently been discovered between XIAP and NF-κB pathways, but the effects of these inhibitors in combination have not been investigated yet. We have studied possible synergistic effects of embelin in combination with celastrol, in an acute myeloid leukemia model, HL-60 cell line. Cytotoxicity of embelin and celastrol, separately and in combination, was determined by MTT assay and flow cytometry. Chou-Talalay's method was used to assess the synergistic effect of two components. Immunocytochemistry and western blot analysis of the two tumor marker proteins. (survivin and COX-2) was also performed to investigate downstream effects of two components. Analysis of MTT assay and flow cytometry showed that there is a substantial synergistic effect in some affected fractions of drug-treated HL-60. cells, while in other affected fractions a mild synergism or additive effect was observed. Immunocytochemistry and western blot analysis revealed that the expression of survivin and COX-2 proteins was reduced in treated cells. Embelin and celastrol showed potent antitumor activity and synergistic effects in combination. Therefore targeting XIAP and NF-κB pathways simultaneously can be investigated in more detail to make use of embelin and celastrol as a combination therapy of cancer.

Cytotoxic Properties of Three Isolated Coumarin-hemiterpene Ether Derivatives from Artemisia armeniaca Lam.

PubMed

Mojarrab, Mahdi; Emami, Seyed Ahmad; Delazar, Abbas; Tayarani-Najaran, Zahra

2017-01-01

Considering multiple reports on cytotoxic activity of the Artemisia genus and its phytochemicals, in the current study A. armeniaca Lam. and the three components isolated from the plant were subjected to cytotoxic studies. Analytical fractionation of A. armeniaca aerial parts for the first time was directed to the isolation of 7-hydroxy-8-(4-hydroxy-3-methylbutoxy) comarin (armenin), 8-hydroxy-7-(4-hydroxy-3-methylbutoxy) comarin (isoarmenin) and deoxylacarol. Cytotoxicity assessed with alamalBlue® assay and apoptosis was detected by PI staining and western blot analysis of Bax and PARP proteins. Extracts and all compounds exhibited cytotoxic activity against apoptosis-proficient HL-60 and apoptosis-resistant K562 cells, with the lowest cytotoxic activity on J774 cell line as non-malignant cell. Armenin as the most potent component decreased the viability of cell with IC50 of 22.5 and 71.1 µM for K562 and HL-60 cells respectively and selected for further mechanistic study. Armenin increased the sub-G1 peak in flow cytometry histogram of HL-60 and K562 treated cells and increase in the amount of Bax protein and the cleavage of PARP in comparison with the control after treatment for 48 h in K562 treated cells verified the apoptotic activity of the armenin. Taken together, according to the finding of this study armenin was introduced as a novel cytotoxic compound with apoptotic activity, which is encouraging for further mechanistic and clinical studies.

An improved equivalent circuit model of a four rod deflecting cavity

NASA Astrophysics Data System (ADS)

Apsimon, R.; Burt, G.

2017-03-01

In this paper we present an improved equivalent circuit model for a four rod deflecting cavity which calculates the frequencies of the first four modes of the cavity as well as the RT/Q for the deflecting mode. Equivalent circuit models of RF cavities give intuition and understanding about how the cavity operates and what changes can be made to modify the frequency, without the need for RF simulations, which can be time-consuming. We parameterise a generic four rod deflecting cavity into a geometry consisting of simple shapes. Equations are derived for the line impedance of the rods and the capacitance between the rods and these are used to calculate the resonant frequency of the deflecting dipole mode as well as the lower order mode and the model is bench-marked against two test cases; the CEBAF separator and the HL-LHC 4-rod LHC crab cavity. CST and the equivalent circuit model agree within 4% for both cavities with the LOM frequency and within 1% for the deflecting frequency. RT/Q differs between the model and CST by 37% for the CEBAF separator and 25% for the HL-LHC 4-rod crab cavity; however this is sufficient for understanding how to optimise the cavity design. The model has then been utilised to suggest a method of separating the modal frequencies in the HL-LHC crab cavity and to suggest design methodologies to optimise the cavity geometries.

[Effect of Inhibiting and Activating Wnt Signalling Pathway on NSC67657-inducing Monocytic Differentiation of HL-60 Cells].

PubMed

Wang, Wei-Jia; Zhang, Xiu-Ming; Zhang, Yan; Wang, Jin-Shu

2016-04-01

To investigate the effect of inhibiting and activating Wnt signalling pathway on monocyte differentiation of HL-60 cells induced with a new steroidal drug NSC67657 and its possible mechamism. The HL-60 cells were treated with 5, 10 and 20 µmol/L XAV-939 (inhibitor of Wnt signalling pathway) for 3 days, and with 10, 20 and 30 mmol/L LiCl (activator of Wnt signalling pathway) for 1 day; the expression levels of down-stream genes and proteins of Wnt signolling pathway were detected by RT-PCR and Western blot, respectively; the expression of cell surface differentiation antigen CD14 and early apoptosis of HL-60 cells was detected by flow cytometry, moreover the most suitable concentration of Wnt inhibitor and activator for HL-60 cells was determined. Then the HL-60 cells with inhibited and activated Wnt pathway were treated with NSC67657 of 10 µmol/L for 3 days; the expression levels of CD14 and down-stream target proteins of Wnt signalling pathway in blank control (culture mediam) group, simple NSC67657-treated group, NSC67657 combined with inhibitor group and NSC67657 combined activator group were compared and analyzed. 20 µmol/L XAV-939 and 20 mmol/L LiCl could effectively inhibit and activate Wnt signalling pathway of HL-60 cells respectively, could significantly down- and up-regulate the expression of cyclinD1, TCF1 and c-Jun genes (P < 0.05) and proteins (P < 0.05); moreover, the number of CD10(+) HL-60 cells in these conditions was below 1%, no early apoptosis of HL-60 cells was found. In the simple NSC67657-treated groups, the expression of cyclinD1, TCF1 and c-Jun proteins was down-regulated (P < 0.05), and the percentage of CD14(+) HL-60 cells accounted for 62.13 ± 9.44; after the HL-60 cells were treated with XAV-939, the NSC67657 could more significantly down-regulate the expression of cyclinD1, TCF1 and c-Jun proteins and the percentage of CD14(+) HL-60 cell accounted for 84.17 ± 5.39%, as compared with simple NSC67657-treated group; as compared with blank controls group, the expression of cyclinD1, TCF1 and c-Jun proteins was more obviously down-regulated and the percentage of CD14(+) HL-60 cells decreased to 33.99 ± 8.37% in NSC67657 combined LiC1 streated group, but which were higher than those in simple NSC67657-treated group (P < 0.05). 20 µmol/L XAV-939 and 20 mmol/L LiCl as effective inhabitor and activator of Wnt signalling pathway respectively can significantly down- and up-regulate the expression of Wnt down-stream pathway target genes and proteins. The influence of XAV-939 and LiC1 on differentiation of HL-60 cells induced by NSC67657 suggests that Wnt signalling pathway plays a key role in monocyte differentiction of HL-60 cells induced by NSC67657.

Design, characterization, teratogenicity testing, antibacterial, antifungal and DNA interaction of few high spin Fe(II) Schiff base amino acid complexes

NASA Astrophysics Data System (ADS)

Abdel-Rahman, Laila H.; El-Khatib, Rafat M.; Nassr, Lobna A. E.; Abu-Dief, Ahmed M.; Lashin, Fakhr El-Din

2013-07-01

In this study, new Fe(II) Schiff base amino acid chelates derived from the condensation of o-hydroxynaphthaldehyde with L-alanine, L-phenylalanine, L-aspartic acid, L-histidine and L-arginine were synthesized and characterized via elemental, thermogravimetric analysis, molar conductance, IR, electronic, mass spectra and magnetic moment measurements. The stoichiometry and the stability constants of the complexes were determined spectrophotometrically. Correlation of all spectroscopic data suggested that Schiff bases ligands exhibited tridentate with ONO sites coordinating to the metal ions via protonated phenolic-OH, azomethine-N and carboxylate-O with the general formulae [Fe(HL)2]·nH2O. But in case of L-histidine, the ligand acts as tetradentate via deprotonated phenolic-OH, azomethine-N, carboxylate-O and N-imidazole ring ([FeL(H2O)2]·2H2O), where HL = mono anion and L = dianion of the ligand. The structure of the prepared complexes is suggested to be octahedral. The prepared complexes were tested for their teratogenicity on chick embryos and found to be safe until a concentration of 100 μg/egg with full embryos formation. Moreover, the interaction between CT-DNA and the investigated complexes were followed by spectrophotometric and viscosity measurements. It was found that, the prepared complexes bind to DNA via classical intercalative mode and showed a different DNA activity with the sequence: nhi > nari > nali > nasi > nphali. Furthermore, the free ligands and their complexes are screened for their in vitro antibacterial and antifungal activity against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa and Bacillus cereus and three types of anti fungal cultures, Penicillium purpurogenium, Aspergillus flavus and Trichotheium rosium in order to assess their antimicrobial potential. The results show that the metal complexes are more reactive with respect to their corresponding Schiff base amino acid ligands.

Bardoxolone Methyl and a Related Triterpenoid Downregulate cMyc Expression in Leukemia Cells.

PubMed

Jin, Un-Ho; Cheng, Yating; Zhou, Beiyan; Safe, Stephen

2017-05-01

Structurally related pentacyclic triterpenoids methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate [bardoxolone-methyl (Bar-Me)] and methyl 2-trifluoromethyl-3,11-dioxoolean-1,12-dien-30-oate (CF 3 DODA-Me) contain 2-cyano-1-en-3-one and 2-trifluoromethyl-1-en-3-one moieties, respectively, in their A-rings and differ in the position of their en-one structures in ring C. Only Bar-Me forms a Michael addition adduct with glutathione (GSH) and inhibits IKK β phosphorylation. These differences may be due to steric hindrance by the 11-keto group in CF 3 DODA-Me, which prevents Michael addition by the conjugated en-one in the A-ring. In contrast, both Bar-Me and CF 3 DODA-Me induce reactive oxygen species in HL-60 and Jurkat leukemia cells, inhibit cell growth, induce apoptosis and differentiation, and decrease expression of specificity proteins (Sp) 1, 3, and 4, and cMyc, and these effects are significantly attenuated after cotreatment with the antioxidant GSH. In contrast to solid tumor-derived cells, cMyc and Sp transcriptions are regulated independently and cMyc plays a more predominant role than Sp transcription factors in regulating HL-60 or Jurkat cell proliferation and differentiation compared with that observed in cells derived from solid tumors. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Pertussis toxin permeabilization enhances the traversal of Escherichia coli K1, macrophages, and monocytes in a cerebral endothelial barrier model in vitro.

PubMed

Seidel, Gabriela; Böcker, Kathrin; Schulte, Jessica; Wewer, Corinna; Greune, Lilo; Humberg, Verena; Schmidt, M Alexander

2011-03-01

The occasionally severe neurological complications following the human respiratory tract infection 'whooping cough' have been attributed to pertussis toxin (PT) expressed by the causative agent Bordetella pertussis. Disruption of the endothelial blood-brain barrier (BBB) by PT might facilitate the translocation of immune cells and of hematogenous microbial pathogens. To test this hypothesis, we investigated whether PT enhances the traversal of bacteria employing human brain microvascular endothelial cells (HBMEC) as an in vitro endothelial barrier model. PT incubation significantly increased the translocation of Escherichia coli K1 across the HBMEC barrier. Only intercellular E. coli K1 bacteria could be identified by electron microscopy suggesting paracellular translocation. In addition, the migration of differentiated HL60-derived macrophages and of human monocytic U937 cells through PT-treated HBMEC barriers was also enhanced. In comparison to E. coli C600, E. coli K1 showed prolonged survival in translocated HL60-derived and J774 macrophages as well as in U937 monocytes which suggested a contribution of the 'Trojan horse' mechanism. In summary, our findings demonstrate that the PT-induced permeabilization of endothelial barriers enhances the paracellular transmigration of microbes and immune cells. In vivo, this activity might lower the threshold of bacteremia facilitating secondary cerebral infections and the subsequent development of brain pathologies. Copyright © 2010 Elsevier GmbH. All rights reserved.

Synthesis and spectral characterization of mono- and binuclear copper(II) complexes derived from 2-benzoylpyridine-N4-methyl-3-thiosemicarbazone: Crystal structure of a novel sulfur bridged copper(II) box-dimer

NASA Astrophysics Data System (ADS)

Jayakumar, K.; Sithambaresan, M.; Aiswarya, N.; Kurup, M. R. Prathapachandra

2015-03-01

Mononuclear and binuclear copper(II) complexes of 2-benzoylpyridine-N4-methyl thiosemicarbazone (HL) were prepared and characterized by a variety of spectroscopic techniques. Structural evidence for the novel sulfur bridged copper(II) iodo binuclear complex is obtained by single crystal X-ray diffraction analysis. The complex [Cu2L2I2], a non-centrosymmetric box dimer, crystallizes in monoclinic C2/c space group and it was found to have distorted square pyramidal geometry (Addison parameter, τ = 0.238) with the square basal plane occupied by the thiosemicarbazone moiety and iodine atom whereas the sulfur atom from the other coordinated thiosemicarbazone moiety occupies the apical position. This is the first crystallographically studied system having non-centrosymmetrical entities bridged via thiolate S atoms with Cu(II)sbnd I bond. The tridentate thiosemicarbazone coordinates in mono deprotonated thionic tautomeric form in all complexes except in sulfato complex, [Cu(HL)(SO4)]·H2O (1) where it binds to the metal centre in neutral form. The magnetic moment values and the EPR spectral studies reflect the binuclearity of some of the complexes. The spin Hamiltonian and bonding parameters are calculated based on EPR studies. In all the complexes g|| > g⊥ > 2.0023 and the g values in frozen DMF are consistent with the dx2-y2 ground state. The thermal stabilities of some of the complexes were also determined.

Paclitaxel-loaded folate-coated long circulating and pH-sensitive liposomes as a potential drug delivery system: A biodistribution study.

PubMed

Monteiro, Liziane O F; Fernandes, Renata S; Oda, Caroline M R; Lopes, Sávia C; Townsend, Danyelle M; Cardoso, Valbert N; Oliveira, Mônica C; Leite, Elaine A; Rubello, Domenico; de Barros, André L B

2018-01-01

A range of antitumor agents for cancer treatment is available; however, they show low specificity, which often limit their use. Recently, we have reported the preparation of folate-coated long-circulating and pH-sensitive liposomes (SpHL-folate-PTX) loaded with paclitaxel (PTX), an effective drug for the treatment of solid tumors, including breast cancer. The purpose of this study was to prepare and characterize SpHL-PTX and SpHL-folate-PTX radiolabeled with technetium-99m ( 99m Tc). Biodistribution studies and scintigraphic images were performed after intravenous administration of 99m Tc-PTX, 99m Tc-SpHL-PTX and 99m Tc-SpHL-folate-PTX into healthy and tumor-bearing mice. High radiochemical purity (>98%) and in vitro stability (>90%) were achieved for both liposome formulations. The pharmacokinetic properties of 99m Tc-SpHL-DTPA-PTX and 99m Tc-SpHL-folate-DTPA-PTX decreased in a monophasic manner showing half-life of 400.1 and 541.8min, respectively. Scintigraphic images and biodistribution studies showed a significant uptake in liver, spleen and kidneys, demonstrating these routes as way for excretion. At 8h post-injection, the liposomal tumor uptake was higher than 99m Tc-PTX. Interesting, 4h after administration, the liposome folate coated showed higher tumor-to-muscle ratio than 99m Tc-SpHL-DTPA-PTX and 99m Tc-PTX. In conclusion, the liposomal systems, showed high tumor uptake by scintigraphic images, especially the 99m Tc-SpHL-folate-DTPA-PTX that showed a sustained and higher tumor-to-muscle ratio than non-functionalized liposome, which indicate its feasibility as a PTX delivery system to folate positive tumors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

CD30 downregulation, MMAE resistance, and MDR1 upregulation are all associated with resistance to brentuximab vedotin

PubMed Central

Chen, Robert; Hou, Jessie; Newman, Edward; Kim, Young; Donohue, Cecile; Liu, Xueli; Thomas, Sandra H.; Forman, Stephen J.; Kane, Susan E.

2015-01-01

Brentuximab vedotin (BV) is an antibody-drug conjugate that specifically delivers the potent cytotoxic drug MMAE to CD30-positive cells. BV is FDA-approved for treatment of relapsed/refractory Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL); however, many patients do not achieve complete remission and develop BV resistant disease. We selected for BV-resistant HL (L428) and ALCL (Karpas-299) cell lines using either constant (ALCL) or pulsatile (HL) exposure to BV. We confirmed drug resistance by MTS assay, and analyzed CD30 expression in resistant cells by flow cytometry, qRT-PCR, and Western blotting. We also measured drug exporter expression, MMAE resistance, and intracellular MMAE concentrations in BV-resistant cells. Additionally, tissue biopsy samples from 10 HL and 5 ALCL patients who had relapsed or progressed after BV treatment were analyzed by immunohistocytochemistry for CD30 expression. The resistant ALCL cell line, but not the HL cell line, demonstrated downregulated CD30 expression compared to the parental cell line. In contrast, the HL cell line, but not the ALCL cell line, exhibited MMAE resistance and increased expression of the MDR1 drug exporter compared to the parental line. For both HL and ALCL, samples from patients relapsed/resistant on BV persistently expressed CD30 by immunohistocytochemistry. One HL patient sample expressed MDR1 by immunohistocytochemistry. Although loss of CD30 expression is a possible mode of BV resistance in ALCL in vitro models, this has not been confirmed in patients. MMAE resistance and MDR1 expression are possible modes of BV resistance for HL both in vitro and in patients. PMID:25840583

DNA-assisted oligomerization of pore-forming toxin monomers into precisely-controlled protein channels

PubMed Central

Knechtel, Johann

2017-01-01

Abstract We have developed a novel approach for creating membrane-spanning protein-based pores. The construction principle is based on using well-defined, circular DNA nanostructures to arrange a precise number of pore-forming protein toxin monomers. We can thereby obtain, for the first time, protein pores with specifically set diameters. We demonstrate this principle by constructing artificial alpha-hemolysin (αHL) pores. The DNA/αHL hybrid nanopores composed of twelve, twenty or twenty-six monomers show stable insertions into lipid bilayers during electrical recordings, along with steady, pore size-dependent current levels. Our approach successfully advances the applicability of nanopores, in particular towards label-free studies of single molecules in large nanoscaled biological structures. PMID:29088457

HL-10 pilots assist with pilot entry into lifting body

NASA Technical Reports Server (NTRS)

1969-01-01

Not every moment of a test pilot's day is serious business. In a moment of levity, NASA pilots Bill Dana (left) and John A. Manke try to drag Air Force test pilot Peter Hoag away from the HL-10 lifting body while Air Force Major Jerauld R. Gentry helps from the cockpit. These four men were the principal pilots for the HL-10 program. This was not the only prank involving the HL-10 and its pilots. Once 'Captain Midnight' (Gentry) and the 'Midnight skulkers' sneaked into the NASA hangar and put 'U.S. Air Force' on the aircraft using stick-on letters. Later, while Gentry was making a lifting-body flight, his 1954 Ford was 'borrowed' from the parking lot, painted with yellow-green zinc-chromate primer, and decorated with large stick-on flowers about one foot in diameter. After Gentry returned from the flight, he was surprised to see what had happened to his car. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Low-load resistance training with low relative pressure produces muscular changes similar to high-load resistance training.

PubMed

Kim, Daeyeol; Loenneke, Jeremy P; Ye, Xin; Bemben, Debra A; Beck, Travis W; Larson, Rebecca D; Bemben, Michael G

2017-12-01

This study compares the acute and chronic response of high-load resistance training (HL) to low-load resistance training with low blood flow restriction (LL-BFR) pressure. Participants completed elbow flexion with either HL or LL-BFR or nonexercise. In the chronic study, participants in the HL and LL-BFR groups were trained for 8 weeks to determine differences in muscle size and strength. The acute study examined the changes in pretesting/posttesting (Pre/Post) torque, muscle swelling, and blood lactate. In the chronic study, similar changes in muscle size and strength were observed for both HL and LL-BFR. In the acute study, Pre/Post changes in the torque, muscle swelling, and blood lactate were similar between HL and LL-BFR. Our findings indicate that pressure as low as 50% arterial occlusion can produce similar changes in muscle mass and strength compared with traditional HL. Muscle Nerve 56: E126-E133, 2017. © 2017 Wiley Periodicals, Inc.

Efflux of hydraulically lifted water from mycorrhizal fungal hyphae during imposed drought

PubMed Central

Querejeta, José Ignacio; Allen, Michael F

2008-01-01

Apart from improving plant and soil water status during drought, it has been suggested that hydraulic lift (HL) could enhance plant nutrient capture through the flow of mineral nutrients directly from the soil to plant roots, or by maintaining the functioning of mycorrhizal fungi. We evaluated the extent to which the diel cycle of water availability created by HL covaries with the efflux of HL water from the tips of extramatrical (external) mycorrhizal hyphae, and the possible effects on biogeochemical processes. Phenotypic mycorrhizal fungal variables, such as total and live hyphal lengths, were positively correlated with HL efflux from hyphae, soil water potential (dawn), and plant response variables (foliar 15N). The efflux of HL water from hyphae was also correlated with bacterial abundance and soil enzyme activity (P), and the moistening of soil organic matter. Such findings indicate that the efflux of HL water from the external mycorrhizal mycelia may be a complementary explanation for plant nutrient acquisition and survival during drought. PMID:19704776

Endogenous thermoregulatory rhythms of squirrel monkeys in thermoneutrality and cold

NASA Technical Reports Server (NTRS)

Robinson, E. L.; Fuller, C. A.

1999-01-01

Whole body heat production (HP) and heat loss (HL) were examined to determine if the free-running circadian rhythm in body temperature (Tb) results from coordinated changes in HP and HL rhythms in thermoneutrality (27 degrees C) as well as mild cold (17 degrees C). Squirrel monkey metabolism (n = 6) was monitored by both indirect and direct calorimetry, with telemetered measurement of Tb and activity. Feeding was also measured. Rhythms of HP, HL, and conductance were tightly coupled with the circadian Tb rhythm at both ambient temperatures (TA). At 17 degrees C, increased HP compensated for higher HL at all phases of the Tb rhythm, resulting in only minor changes to Tb. Parallel compensatory changes of HP and HL were seen at all rhythm phases at both TA. Similar time courses of Tb, HP, and HL in their respective rhythms and the relative stability of Tb during both active and rest periods suggest action of the circadian timing system on Tb set point.

More than Use it or Lose it: The Number of Speakers Effect on Heritage Language Proficiency

PubMed Central

Gollan, Tamar H.; Starr, Jennie; Ferreira, Victor S.

2014-01-01

Acquiring a Heritage Language (HL), a minority language spoken primarily at home, is often a major step toward achieving bilingualism. Two studies examined factors that promote HL proficiency. Chinese-English and Spanish-English undergraduates and Hebrew-English children named pictures in both their languages, and they or their parents completed language history questionnaires. HL picture-naming ability correlated positively with the number of different HL speakers participants spoke to as children, independent of each language’s frequency of use, and without negatively affecting English picture naming ability. HL performance increased also when primary caregivers had lower English proficiency, with later English age-of-acquisition, and (in children) with increased age. These results suggest a prescription for increasing bilingual proficiency is regular interaction with multiple HL speakers. Responsible cognitive mechanisms could include greater variety of words used by different speakers, representational robustness from exposure to variations in form, or multiple retrieval cues, perhaps analogous to contextual diversity effects. PMID:24942146

HL-10 on lakebed showing subsonic control surface configuration

NASA Technical Reports Server (NTRS)

1966-01-01

This photo shows the HL-10 on lakebed with its subsonic control surface configuration. The unusual shapes of the lifting bodies, as well as the demands of flying a re-entry shape to comparative low-speed landings, required a complex set of control surfaces. The rudders also served as speed brakes, allowing the pilot to adjust his speed during descent. Moving the flaps at the rear of the fuselage in the same direction pitched the nose up, while moving them in opposite directions rolled the vehicle to the right or left. After the HL-10's fins were modified to improve its handling qualities, the vehicle proved to be the best handling of the original heavy-weight lifting bodies. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

A new (4, 6)-connected Cu(I) coordination polymer based on rare tetranuclear [Cu4I2] clusters: Synthesis, crystal structure, luminescent and photocatalytic properties

NASA Astrophysics Data System (ADS)

Cui, Li-Jing; Liu, Chun-Yan; Bian, Ming; Yu, Li-Jun

2018-03-01

A new Cu(I) coordination polymer, namely [Cu5I3(L)2]n (1 HL = 3-(4-pyridyl)-5-(3-pyridyl)-1,2,4-triazolyl), was solvothermally synthesized using CuI, HL and NaI as the starting materials. Single crystal X-ray structural analysis shows that compound 1 features a (4, 6)-connected 3D framework employing rare tetranuclear [Cu4I2] clusters as building subunits. It exhibits intense metal-to-ligand luminescence and excellent photocatalytic activity on degradation of methylene blue (MB).

Clinical Features and Prognostic Factors of Hodgkin’s Lymphoma: A Single Center Experience

PubMed Central

Kılıçkap, Saadettin; Barışta, İbrahim; Ülger, Şükran; Çelik, İsmail; Selek, Uğur; Yıldız, Ferah; Kars, Ayşe; Özışık, Yavuz; Tekuzman, Gülten

2013-01-01

Background: Hodgkin’s lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. Aims: We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. Study Design: Retrospective study. Methods: Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. Results: We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of “B” symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. Conclusion: This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country. PMID:25207097

Fine Mapping and Transcriptome Analysis Reveal Candidate Genes Associated with Hybrid Lethality in Cabbage (Brassica Oleracea).

PubMed

Xiao, Zhiliang; Hu, Yang; Zhang, Xiaoli; Xue, Yuqian; Fang, Zhiyuan; Yang, Limei; Zhang, Yangyong; Liu, Yumei; Li, Zhansheng; Liu, Xing; Liu, Zezhou; Lv, Honghao; Zhuang, Mu

2017-06-05

Hybrid lethality is a deleterious phenotype that is vital to species evolution. We previously reported hybrid lethality in cabbage ( Brassica oleracea ) and performed preliminary mapping of related genes. In the present study, the fine mapping of hybrid lethal genes revealed that BoHL1 was located on chromosome C1 between BoHLTO124 and BoHLTO130, with an interval of 101 kb. BoHL2 was confirmed to be between insertion-deletion (InDels) markers HL234 and HL235 on C4, with a marker interval of 70 kb. Twenty-eight and nine annotated genes were found within the two intervals of BoHL1 and BoHL2 , respectively. We also applied RNA-Seq to analyze hybrid lethality in cabbage. In the region of BoHL1 , seven differentially expressed genes (DEGs) and five resistance (R)-related genes (two in common, i.e., Bo1g153320 and Bo1g153380 ) were found, whereas in the region of BoHL2 , two DEGs and four R-related genes (two in common, i.e., Bo4g173780 and Bo4g173810 ) were found. Along with studies in which R genes were frequently involved in hybrid lethality in other plants, these interesting R-DEGs may be good candidates associated with hybrid lethality. We also used SNP/InDel analyses and quantitative real-time PCR to confirm the results. This work provides new insight into the mechanisms of hybrid lethality in cabbage.

An oncogenic axis of STAT-mediated BATF3 upregulation causing MYC activity in classical Hodgkin lymphoma and anaplastic large cell lymphoma.

PubMed

Lollies, A; Hartmann, S; Schneider, M; Bracht, T; Weiß, A L; Arnolds, J; Klein-Hitpass, L; Sitek, B; Hansmann, M-L; Küppers, R; Weniger, M A

2018-01-01

Classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) feature high expression of activator protein-1 (AP-1) transcription factors, which regulate various physiological processes but also promote lymphomagenesis. The AP-1 factor basic leucine zipper transcription factor, ATF-like 3 (BATF3), is highly transcribed in cHL and ALCL; however, its functional importance in lymphomagenesis is unknown. Here we show that proto-typical CD30 + lymphomas, namely cHL (21/30) and primary mediastinal B-cell lymphoma (8/9), but also CD30 + diffuse large B-cell lymphoma (15/20) frequently express BATF3 protein. Mass spectrometry and co-immunoprecipitation established interactions of BATF3 with JUN and JUNB in cHL and ALCL lines. BATF3 knockdown using short hairpin RNAs was toxic for cHL and ALCL lines, reducing their proliferation and survival. We identified MYC as a critical BATF3 target and confirmed binding of BATF3 to the MYC promoter. JAK/STAT signaling regulated BATF3 expression, as chemical JAK2 inhibition reduced and interleukin 13 stimulation induced BATF3 expression in cHL lines. Chromatin immunoprecipitation substantiated a direct regulation of BATF3 by STAT proteins in cHL and ALCL lines. In conclusion, we identified STAT-mediated BATF3 expression that is essential for lymphoma cell survival and promoted MYC activity in cHL and ALCL, hence we recognized a new oncogenic axis in these lymphomas.

Measuring the effects of heat wave episodes on the human body's thermal balance

NASA Astrophysics Data System (ADS)

Katavoutas, George; Theoharatos, George; Flocas, Helena A.; Asimakopoulos, Dimosthenis N.

2009-03-01

During the peak of an extensive heat wave episode on 23-25 July 2007, simultaneous thermophysiological measurements were made in two non-acclimated healthy adults of different sex in a suburban area of Greater Athens, Greece. Based on experimental measurements of mean skin temperature and metabolic heat production, heat fluxes to and from the human body were calculated, and the biometeorological index heat load (HL) produced was determined according to the heat balance equation. Comparing experimental values with those derived from theoretical estimates revealed a great heat stress for both individuals, especially the male, while theoretical values underestimated heat stress. The study also revealed that thermophysiological factors, such as mean skin temperature and metabolic heat production, play an important role in determining heat fluxes patterns in the heat balance equation. The theoretical values of mean skin temperature as derived from an empirical equation may not be appropriate to describe the changes that take place in a non-acclimated individual. Furthermore, the changes in metabolic heat production were significant even for standard activity.

HL-10 on lakebed with pilot Bill Dana

NASA Technical Reports Server (NTRS)

1966-01-01

NASA research pilot Bill Dana stands in front of the HL-10 Lifting Body following his first glide flight on April 25, 1969. Dana later retired Chief Engineer at NASA's Dryden Flight Research Center, which was called only the NASA Flight Research Center in 1969. Prior to his lifting body assignment, Dana flew the famed X-15 research airplane. He flew the rocket-powered aircraft 16 times, reaching a top speed of 3,897 miles per hour and a peak altitude of 310,000 feet (almost 59 miles high). The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Strategies for genetic study of hearing loss in the Brazilian northeastern region

PubMed Central

Melo, Uirá S; Santos, Silvana; Cavalcanti, Hannalice G; Andrade, Wagner T; Dantas, Vitor G; Rosa, Marine RD; Mingroni-Netto, Regina C

2014-01-01

The overall aim of this study was to estimate the contribution of genetic factors to the etiology of hearing loss (HL) in two counties in the Brazilian northeastern region. A cross-sectional study, based on the key informant approach (KI) was conducted in Queimadas and Gado Bravo counties (Paraíba, Northeast Brazil). The sample consisted of 182 patients with HL. Genetic screening of the most frequent mutations associated with HL was performed for all samples. DFNB1 mutations were the most frequently found in both counties. The c.35delG mutation was detected in homozygosis in seven non-syndromic probands in Queimadas (7/76, 9.2%) and only a single homozygote with this mutation was found in Gado Bravo (1/44, 2.3%). We also detected the del(GJB6-D13S1854) mutation in non-syndromic probands from Gado Bravo (2/44, 4.5%). The c.189C>A (p.TyrY63*) mutation in the CLRN1 gene was detected in homozygosis in 21/23 Usher syndrome patients from Gado Bravo and it was not found in Queimadas. Cases with probable genetic etiology contributed approximately to half of HL probands in each county (54.6% in Gado Bravo and 45.7% in Queimadas). We confirm the importance of DFNB1 locus to non-syndromic HL but we show that the frequency of mutations in the northeastern region differs somewhat from those reported in southeastern Brazil and other populations. In addition, the extremely high frequency of individuals with Usher syndrome with c.189C>A variation in CLRN1 indicates the need for a specific screening of this mutation. PMID:24596593

Prognostic markers in feline hepatic lipidosis: a retrospective study of 71 cats.

PubMed

Kuzi, Sharon; Segev, Gilad; Kedar, Shay; Yas, Einat; Aroch, Itamar

2017-11-11

Feline hepatic lipidosis (HL) is a common, potentially life-threatening disease resulting from prolonged anorexia and increased catabolism. This retrospective study included cats diagnosed with HL based on liver cytology or histopathology (years 2004-2015), and aimed to identify clinical and laboratory parameters associated with mortality. The study included 71 cats (47 females and 24 males) and 85 control cats with non-HL diseases. Most HL cats (90 per cent) were mixed breed, neutered (70; 99 per cent), female (47; 66 per cent), indoor cats (56; 79 per cent), fed dry commercial diets (44 cats; 62 per cent), and with a median age of 7.5 years (range 1.5-16.0). Common primary conditions included gastrointestinal diseases, pancreatitis and cholangiohepatitis (31 cats; 44 per cent) and stressful events (14; 20 per cent). HL was idiopathic in 20 cats (28 per cent). The overall mortality was 38 per cent (27/71 cats). Older age, as well as dullness, weakness, ptyalism, hypoproteinaemia, hypoalbuminaemia, increased serum creatine kinase activity, hypocholesterolaemia and hepatic failure at presentation were significantly (P≤0.033) associated with mortality. The primary disease was unassociated with mortality. Worsening hypoalbuminaemia, hyperammonaemia, hyperbilirubinaemia, electrolyte disorders, and occurrence of cavitary effusions or hypotension during hospitalisation were significantly (P≤0.045) associated with mortality. A decrease of serum β-hydroxybutyrate during hospitalisation was significantly (P=0.01) associated with survival, likely reflecting improvement in the catabolic state. The identified risk factors may be therapeutic targets. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The impact of health and health insurance literacy on access to care for Hispanic/Latino communities.

PubMed

Edward, Jean; Morris, Sarah; Mataoui, Fatma; Granberry, Phillip; Williams, Mark V; Torres, Idali

2018-05-01

The aim of this study was to assess the impact of health literacy (HL) and health insurance literacy (HIL) on health insurance status and access to health care services for Spanish-speaking communities living in Massachusetts. A total of 139 surveys (descriptive, knowledge-based HIL questions, and Short Assessment of Health Literacy in Spanish) and 30 semi-structured interviews were collected and analyzed using chi-square, Mann-Whitney U test, and logistic regression analysis. The majority of participants had inadequate HL (56%) and HIL (93%). There were differences in HL scores (t = 4.1; p < .0001) between the insured (M = 12.3, SD = 5.7) and uninsured (M = 7.9, SD = 6.7) and differences (t = 1.9; p = .05) between those with adequate HIL (M = 14.3, SD = 4.3) and inadequate HIL (M = 10.2, SD = 6.6). Participants who were uninsured (MW U = 37.6; p < .0001) and who had inadequate HL (MW U = 5.2; p = .02) were more likely to have never accessed health care in the U.S. Participants who had never accessed health care were 93% less likely to be insured and those with adequate HL were three times more likely to be insured. Health literacy and HIL are closely associated with insurance status and access to health care for Spanish-speaking communities, indicating the need for further research and enhanced public health efforts to improve knowledge and awareness around navigating health care systems. © 2018 Wiley Periodicals, Inc.

The Neuromuscular Qualities of Higher- and Lower-Level Mixed-Martial-Arts Competitors.

PubMed

James, Lachlan P; Beckman, Emma M; Kelly, Vincent G; Haff, G Gregory

2017-05-01

To determine whether the maximal strength, impulse, and power characteristics of competitive mixed-martial-arts (MMA) athletes differ according to competition level. Twenty-nine male semiprofessional and amateur MMA competitors were stratified into either higher-level (HL) or lower-level (LL) performers on the basis of competition grade and success. The 1-repetition-maximum (1RM) squat was used to assess lower-body dynamic strength, and a spectrum of impulse, power, force, and velocity variables were evaluated during an incremental-load jump squat. In addition, participants performed an isometric midthigh pull (IMTP) and 1RM bench press to determine whole-body isometric force and upper-body dynamic strength capabilities, respectively. All force and power variables were expressed relative to body mass (BM). The HL competitors produced significantly superior values across a multitude of measures. These included 1RM squat strength (1.84 ± 0.23 vs 1.56 ± 0.24 kg BM; P = .003), in addition to performance in the incremental-load jump squat that revealed greater peak power (P = .005-.002), force (P = .002-.004), and velocity (P = .002-.03) at each load. Higher measures of impulse (P = .01-.04) were noted in a number of conditions. Average power (P = .002-.02) and velocity (P = .01-.04) at all loads in addition to a series of rate-dependent measures were also superior in the HL group (P = .005-.02). The HL competitors' 1RM bench-press values approached significantly greater levels (P = .056) than the LL group's, but IMTP performance did not differ between groups. Maximal lower-body neuromuscular capabilities are key attributes distinguishing HL from LL MMA competitors. This information can be used to inform evidenced-based training and performance-monitoring practices.

Developing and flight testing the HL-10 lifting body: A precursor to the Space Shuttle

NASA Technical Reports Server (NTRS)

Kempel, Robert W.; Painter, Weneth D.; Thompson, Milton O.

1994-01-01

The origins of the lifting-body idea are traced back to the mid-1950's, when the concept of a manned satellite reentering the Earth's atmosphere in the form of a wingless lifting body was first proposed. The advantages of low reentry deceleration loads, range capability, and horizontal landing of a lifting reentry vehicle (as compared with the high deceleration loads and parachute landing of a capsule) are presented. The evolution of the hypersonic HL-10 lifting body is reviewed from the theoretical design and development process to its selection as one of two low-speed flight vehicles for fabrication and piloted flight testing. The design, development, and flight testing of the low-speed, air-launched, rocket-powered HL-10 was part of an unprecedented NASA and contractor effort. NASA Langley Research Center conceived and developed the vehicle shape and conducted numerous theoretical, experimental, and wind-tunnel studies. NASA Flight Research Center (now NASA Dryden Flight Research Center) was responsible for final low-speed (Mach numbers less than 2.0) aerodynamic analysis, piloted simulation, control law development, and flight tests. The prime contractor, Northrop Corp., was responsible for hardware design, fabrication, and integration. Interesting and unusual events in the flight testing are presented with a review of significant problems encountered in the first flight and how they were solved. Impressions by the pilots who flew the HL-10 are included. The HL-10 completed a successful 37-flight program, achieved the highest Mach number and altitude of this class vehicle, and contributed to the technology base used to develop the space shuttle and future generations of lifting bodies.

New heteroleptic Zn(II) complexes of thiosemicarbazone and diimine Co-Ligands: Structural analysis and their biological impacts

NASA Astrophysics Data System (ADS)

Mathan Kumar, Shanmugaiah; Kesavan, Mookkandi Palsamy; Vinoth Kumar, Gujuluva Gangatharan; Sankarganesh, Murugesan; Chakkaravarthi, Ganesan; Rajagopal, Gurusamy; Rajesh, Jegathalaprathaban

2018-02-01

A thiosemicarbazone ligand HL appended new Zn(II) complexes [Zn(L)(bpy)] (1) and [Zn(L)(phen)] (2) (where, HL = {2-(3-bromo-5-chloro-2-hydroxybenzylidene)-N-phenylhydrazinecarbothioamide}, bpy = 2, 2‧-bipyridine and phen = 1, 10-phenanthroline) have been synthesized and well characterized using conventional spectroscopic techniques viz.,1H NMR, FTIR and UV-Vis spectra. The crystal structures of complexes 1 and 2 have been determined by single crystal X-ray diffraction studies. Both the complex 1 (τ = 0.5) and 2 (τ = 0.37) possesses square based pyramidally distorted trigonal bipyramidal geometry. The ground state electronic structures of complexes 1 and 2 were investigated by DFT/B3LYP theoretical analysis using 6-311G (d,p) and LANL2DZ basis set level. The superior DNA binding ability of complex 2 has been evaluated using absorption and fluorescence spectral titration studies. Antimicrobial evaluation reveals that complex 2 endowed better screening than HL and complex 1 against both bacterial as well as fungal species. Consequently, complex 2 possesses highest antibacterial screening against Staphylococcus aureus (MIC = 3.0 ± 0.23 mM) and antifungal screening against Candida albicans (MIC = 6.0 ± 0.11 mM). Furthermore, the anticancer activity of the ligand HL, complexes 1 and 2 have been examined against the MCF-7 cell line (Human breast cancer cell line) using MTT assay. It is remarkable that complex 2 (12 ± 0.67 μM) show highest anticancer activity than HL (25.0 ± 0.91 μM) and complex 1 (15 ± 0.88 μM) due to the presence of phen ligand moiety.

Dehalogenation Activity of Selected Fungi Toward δ-Iodo-γ-Lactone Derived from trans,trans-Farnesol.

PubMed

Gliszczyńska, Anna; Gładkowski, Witold; Świtalska, Marta; Wietrzyk, Joanna; Szumny, Antoni; Gębarowska, Elżbieta; Wawrzeńczyk, Czesław

2016-04-01

Time-course of biotransformation of racemic trans-4-((E)-4',8'-dimethylnona-3',7'-dien-1-yl)-5-iodomethyl-4-methyldihydrofuran-2-one (1) in fungal and yeast cultures was investigated. In these conditions, the substrate 1 was enantioselectively dehalogenated yielding 4-((E)-4',8'-dimethylnona-3',7'-dien-1-yl)-4-methyl-5-methylenedihydrofuran-2-one (2) and its structure was established based on the spectroscopic data. The most effective biocatalyst used was Didymosphaeria igniaria, which catalyzed the process with highest rate and enantioselectivity (ee of product = 76%). The antiproliferative activity of δ-iodo-γ-lactone 1, product of its biotransformation 2, and starting substrate (farnesol) were evaluated toward two cancer cell lines: A549 (human lung adenocarcinoma) and HL-60 (human promyelocytic leukemia). © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Checkpoint Inhibition in Hodgkin Lymphoma - a Review.

PubMed

Bröckelmann, Paul J; Engert, Andreas

2017-01-01

Physiological immune checkpoint pathways are important to regulate self-tolerance, limit immune reactions, and moderate autoimmunity. Various cancers are commonly exploiting these mechanisms to evade the host immune system by restraining a durable, efficient anti-tumor immune response. Immune checkpoints include, but are not limited to, the programmed death 1 (PD1) and the cytotoxic T-lymphocyte-associated protein-4 (CTLA4) axis, which are both druggable by monoclonal antibodies referred to as checkpoint inhibitors (CIs). To date, the anti-PD1 antibodies nivolumab and pembrolizumab are approved for relapsed or refractory classical Hodgkin lymphoma (cHL) due to high response rates with a favorable yet distinct safety profile, and other agents are under investigation. This review summarizes the available preclinical and clinical data including the toxicity and efficacy of different CIs in cHL. It also provides future perspectives based on ongoing clinical trials, potentially synergistic combinatory approaches, and their fit in the therapeutic landscape in cHL. © 2017 S. Karger GmbH, Freiburg.

Isolation of furocoumarins from bergamot fruits as HL-60 differentiation-inducing compounds.

PubMed

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

1999-10-01

The HL-60 differentiation-inducing compounds in bergamot fruits were isolated with column chromatography and identified as bergamottin, bergapten, and citropten by (1)H and (13)C NMR. Their HL-60 differentiation-inducing activity was measured by examining nitro blue tetrazolium (NBT) reducing, nonspecific acid esterase (NSE), specific esterase (SE), and phagocytic activities, and bergamottin showed the strongest activity among the coumarins isolated from bergamot fruits. The structure-activity relationship obtained from HL-60 differentiation assay suggests that hydrophobicity of furocoumarins is correlated with their activity.

Effect of coumarins on HL-60 cell differentiation.

PubMed

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

2000-01-01

Twenty-eight coumarins, including 7 furocoumarins, were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase and phagocytic activities. Esculetin, nordalbergin, 6,7-dihydroxy-4-methylcoumarin and imperatorin had strong activity among the coumarins examined. HL-60 cells treated with these coumarins differentiated into mature monocyte/macrophage. The structure-activity relationship established from the results revealed that 6,7-dihydroxy moiety had an important role in the induction of differentiation of HL-60.

Relationship between health literacy, health information access, health behavior, and health status in Japanese people.

PubMed

Suka, Machi; Odajima, Takeshi; Okamoto, Masako; Sumitani, Masahiko; Igarashi, Ataru; Ishikawa, Hirono; Kusama, Makiko; Yamamoto, Michiko; Nakayama, Takeo; Sugimori, Hiroki

2015-05-01

To examine the relationship between health literacy (HL), health information access, health behavior, and health status in Japanese people. A questionnaire survey was conducted at six healthcare facilities in Japan. Eligible respondents aged 20-64 years (n=1218) were included. Path analysis with structural equation modeling was performed to test the hypothesis model linking HL to health information access, health behavior, and health status. The acceptable fitting model indicated that the pathways linking HL to health status consisted of two indirect paths; one intermediated by health information access and another intermediated by health behavior. Those with higher HL as measured by the 14-item Health Literacy Scale (HLS-14) were significantly more likely to get sufficient health information from multiple sources, less likely to have risky habits of smoking, regular drinking, and lack of exercise, and in turn, more likely to report good self-rated health. HL was significantly associated with health information access and health behavior in Japanese people. HL may play a key role in health promotion, even in highly educated countries like Japan. In order to enhance the effects of health promotion interventions, health professionals should aim at raising HL levels of their target population groups. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Synthesis, characterization and biological activities of some Ru(II) complexes with substituted chalcones and their applications as chemotherapeutics against breast cancer

NASA Astrophysics Data System (ADS)

Singh, Ashok K.; Saxena, Gunjan; Dixit, Shivani; Hamidullah; Singh, Sachin K.; Singh, Sudheer K.; Arshad, M.; Konwar, Rituraj

2016-05-01

Four new Ru(II) DMSO complexes with substituted chalcone ligands viz. (E)-1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (HL1), (E)-1-(2-hydroxyphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (HL2), (E)-3-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (HL3) and (E)-1-(2-hydroxyphenyl)-3-(4-Chlorophenyl)prop-2-en-1-one (HL4) have been synthesized, and characterized by micro-analyses, IR, 1H NMR, UV-Vis and ESI-MS and screened for anti-cancer activity against breast cancer cell lines (MCF-7 and MDA MB-231). Compounds HL4 and [Ru(HL1) (O-DMSO)3(S-DMSO)]Cl (M1R) showed significant anti-breast cancer activity as evident from cytotoxicity, morphological and nuclear changes, DNA fragmentation and cell cycle arrest in breast cancer cells. UV-Vis and CD-spectra analysis showed HL4 and M1R interfered with DNA absorption spectra possibly due to DNA binding whereas these compounds were devoid of DNA topoisomerase inhibiting activity. Thus, these Ru(II) compounds have been established as new leads for future optimization by improving anti-cancer potency and safety.

Raman spectrum reveals Mesenchymal stem cells inhibiting HL60 cells growth

NASA Astrophysics Data System (ADS)

Su, Xin; Fang, Shaoyin; Zhang, Daosen; Zhang, Qinnan; Lu, Xiaoxu; Tian, Jindong; Fan, Jinping; Zhong, Liyun

2017-04-01

Though some research results reveals that Mesenchymal stem cells (MSCs) have the ability of inhibiting tumor cells proliferation, it remains controversial about the precise interaction mechanism during MSCs and tumor cells co-culture. In this study, combing Raman spectroscopic data and principle component analysis (PCA), the biochemical changes of MSCs or Human promyelocytic leukemia (HL60) cells during their co-culture were presented. The obtained results showed that some main Raman peaks of HL60 assigned to nucleic acids or proteins were greatly higher in intensity in the late stage of co-culture than those in the early stage of co-culture while they were still lower relative to the control group, implicating that the effect of MSCs inhibiting HL60 proliferation appeared in the early stage but gradually lost the inhibiting ability in the late stage of co-culture. Moreover, some other peaks of HL60 assigned to proteins were decreased in intensity in the early stage of co-culture relative to the control group but rebounded to the level similar to the control group in the late stage, showing that the content and structure changes of these proteins might be generated in the early stage but returned to the original state in the late stage of co-culture. As a result, in the early stage of MSCs-HL60 co-culture, along with the level of Akt phosphorylation of HL60 was lowered relative to its control group, the proliferation rate of HL60 cells was decreased. And in the late stage of co-culture, along with the level of Akt phosphorylation was rebounded, the reverse transfer of Raman peaks within 875-880 cm- 1 appeared, thus MSCs lost the ability to inhibit HL60 growth and HL60 proliferation was increased. In addition, it was observed that the peak at 811 cm- 1, which is a marker of RNA, was higher in intensity in the late stage than that in the control group, indicating that MSCs might be differentiated into myofibroblast-like MSCs. In addition, PCA results also exhibited that the physiological state of MSCs can be separated by the first two main components of PC1 or PC2 easily, and the effect of MSCs inhibiting HL60 growth was greatly associated with the time of co-culture.

1D and 2D assembly structures by imidazole···chloride hydrogen bonds of iron(II) complexes [Fe(II)(HL(n-Pr))3]Cl·Y (HL(n-Pr) = 2-methylimidazol-4-yl-methylideneamino-n-propyl; Y = AsF6, BF4) and their spin states.

PubMed

Fujinami, Takeshi; Nishi, Koshiro; Matsumoto, Naohide; Iijima, Seiichiro; Halcrow, Malcolm A; Sunatsuki, Yukinari; Kojima, Masaaki

2011-12-07

Two Fe(II) complexes fac-[Fe(II)(HL(n-Pr))(3)]Cl·Y (Y = AsF(6) (1) and BF(4) (2)) were synthesized, where HL(n-Pr) is 2-methylimidazole-4-yl-methylideneamino-n-propyl. Each complex-cation has the same octahedral N(6) geometry coordinated by three bidentate ligands and assumes facial-isomerism, fac-[Fe(II)(HL(n-Pr))(3)](2+) with Δ- and Λ-enantiomorphs. Three imidazole groups per Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) are hydrogen-bonded to three Cl(-) ions or, from the viewpoint of the Cl(-) ion, one Cl(-) ion is hydrogen-bonded to three neighbouring fac-[Fe(II)(HL(n-Pr))(3)](2+) cations. The 3 : 3 NH···Cl(-) hydrogen bonds between Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) and Cl(-) generate two kinds of assembly structures. The directions of the 3 : 3 NH···Cl(-) hydrogen bonds and hence the resulting assembly structures are determined by the size of the anion Y, though Y is not involved into the network structure and just accommodated in the cavity. Compound 1 has a 1D ladder structure giving a larger cavity, in which the Δ- and Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) enantiomorphs are bridged by two NH···Cl(-) hydrogen bonds. Compound 2 has a 2D network structure with a net unit of a cyclic trimer of {fac-[Fe(II)(HL(n-Pr))(3)](2+)···Cl(-)}(3) giving a smaller cavity, in which Δ- or Λ-fac-[Fe(II)(HL(n-Pr))(3)](2+) species with the same chirality are linked by NH···Cl(-) hydrogen bonds to give a homochiral 2D network structure. Magnetic susceptibility and Mössbauer spectral measurements demonstrated that compound 1 showed an abrupt one-step spin crossover with 4.0 K thermal hysteresis of T(c↓) = 125.5 K and T(c↑) = 129.5 K and compound 2 showed no spin transition and stayed in the high-spin state over the 5-300 K temperature range.

Design and development of a tele-healthcare information system based on web services and HL7 standards.

PubMed

Huang, Ean-Wen; Hung, Rui-Suan; Chiou, Shwu-Fen; Liu, Fei-Ying; Liou, Der-Ming

2011-01-01

Information and communication technologies progress rapidly and many novel applications have been developed in many domains of human life. In recent years, the demand for healthcare services has been growing because of the increase in the elderly population. Consequently, a number of healthcare institutions have focused on creating technologies to reduce extraneous work and improve the quality of service. In this study, an information platform for tele- healthcare services was implemented. The architecture of the platform included a web-based application server and client system. The client system was able to retrieve the blood pressure and glucose levels of a patient stored in measurement instruments through Bluetooth wireless transmission. The web application server assisted the staffs and clients in analyzing the health conditions of patients. In addition, the server provided face-to-face communications and instructions through remote video devices. The platform deployed a service-oriented architecture, which consisted of HL7 standard messages and web service components. The platform could transfer health records into HL7 standard clinical document architecture for data exchange with other organizations. The prototyping system was pretested and evaluated in a homecare department of hospital and a community management center for chronic disease monitoring. Based on the results of this study, this system is expected to improve the quality of healthcare services.

Association between sarcopenia and hearing thresholds in postmenopausal women.

PubMed

Kang, Seok Hui; Jung, Da Jung; Cho, Kyu Hyang; Park, Jong Won; Lee, Kyu-Yup; Do, Jun Young

2017-01-01

Background: Given the association between metabolic disturbance and sarcopenia, sarcopenia may be intrinsically associated with the prevalence of HL. However, few studies describe the association between sarcopenia and HL. The aim of this study was to evaluate the clinical association between sarcopenia and HL in postmenopausal Korean women. Patients and Methods: A total of 4,038 women were ultimately included in this study. All participants were postmenopausal. Participants were divided into two groups based on criteria from the Foundation for the National Institute of Health Sarcopenia Project: a normal group (sarcopenia index ≥ 0.512) and a sarcopenia group (sarcopenia index < 0.512). Low-frequency (Low-Freq), mid-frequency (Mid-Freq), and high-frequency (High-Freq) values were obtained. The average hearing threshold (AHT) was calculated as the pure tone average at the 4 frequencies of 0.5 kHz, 1 kHz, 2 kHz, and 3 kHz. Mild HL was as an AHT of 24 to 40 dB; moderate-to-profound HL was defined as an AHT of 40 dB or greater. Results: Of the 4,038 participants, 272 (6.7%) were allocated to the sarcopenia group, leaving 3,766 (93.3%) in the normal group. The groups differed significantly in terms of having hypertension (775 [20.6%] vs. 108 [39.7%]; P < 0.001) or metabolic syndrome (817 [21.7%] vs. 110 [40.4%]; P < 0.001) in the normal and sarcopenia groups, respectively. Visceral fat area (cm 3 ) in the normal and sarcopenia groups was 99.0 ± 21.9 cm 3 and 117.0 ± 21.8 cm 3 , respectively ( P < 0.001). The hsCRP level was higher in the sarcopenia group than in the normal group. For univariate and multivariate analyses, all 4 hearing thresholds were higher in the sarcopenia group than in the normal group. In addition, linear regression analyses showed Low-Freq, Mid-Freq, and High-Freq to be inversely correlated with the sarcopenia index. The unadjusted OR for mild HL was 2.692 (95% CI, 1.963-3.692; P < 0.001) in the sarcopenia group relative to the normal group, with an adjusted OR of 1.584 (95% CI, 1.131-2.217; P = 0.007). The unadjusted OR for moderate-to-profound HL in the sarcopenia group relative to the normal group was 6.246 (95% CI, 4.530-8.612; P < 0.001); the adjusted OR was 2.667 (95% CI, 1.866-3.812; P < 0.001). Conclusion: Sarcopenia may be associated with HL. It may be beneficial to perform screening audiometry in patients with sarcopenia.

Association between sarcopenia and hearing thresholds in postmenopausal women

PubMed Central

Kang, Seok Hui; Jung, Da Jung; Cho, Kyu Hyang; Park, Jong Won; Lee, Kyu-Yup; Do, Jun Young

2017-01-01

Background: Given the association between metabolic disturbance and sarcopenia, sarcopenia may be intrinsically associated with the prevalence of HL. However, few studies describe the association between sarcopenia and HL. The aim of this study was to evaluate the clinical association between sarcopenia and HL in postmenopausal Korean women. Patients and Methods: A total of 4,038 women were ultimately included in this study. All participants were postmenopausal. Participants were divided into two groups based on criteria from the Foundation for the National Institute of Health Sarcopenia Project: a normal group (sarcopenia index ≥ 0.512) and a sarcopenia group (sarcopenia index < 0.512). Low-frequency (Low-Freq), mid-frequency (Mid-Freq), and high-frequency (High-Freq) values were obtained. The average hearing threshold (AHT) was calculated as the pure tone average at the 4 frequencies of 0.5 kHz, 1 kHz, 2 kHz, and 3 kHz. Mild HL was as an AHT of 24 to 40 dB; moderate-to-profound HL was defined as an AHT of 40 dB or greater. Results: Of the 4,038 participants, 272 (6.7%) were allocated to the sarcopenia group, leaving 3,766 (93.3%) in the normal group. The groups differed significantly in terms of having hypertension (775 [20.6%] vs. 108 [39.7%]; P < 0.001) or metabolic syndrome (817 [21.7%] vs. 110 [40.4%]; P < 0.001) in the normal and sarcopenia groups, respectively. Visceral fat area (cm3) in the normal and sarcopenia groups was 99.0 ± 21.9 cm3 and 117.0 ± 21.8 cm3 , respectively (P < 0.001). The hsCRP level was higher in the sarcopenia group than in the normal group. For univariate and multivariate analyses, all 4 hearing thresholds were higher in the sarcopenia group than in the normal group. In addition, linear regression analyses showed Low-Freq, Mid-Freq, and High-Freq to be inversely correlated with the sarcopenia index. The unadjusted OR for mild HL was 2.692 (95% CI, 1.963-3.692; P < 0.001) in the sarcopenia group relative to the normal group, with an adjusted OR of 1.584 (95% CI, 1.131-2.217; P = 0.007). The unadjusted OR for moderate-to-profound HL in the sarcopenia group relative to the normal group was 6.246 (95% CI, 4.530-8.612; P < 0.001); the adjusted OR was 2.667 (95% CI, 1.866-3.812; P < 0.001). Conclusion: Sarcopenia may be associated with HL. It may be beneficial to perform screening audiometry in patients with sarcopenia. PMID:28539823

Concurrent validation of two key health literacy instruments in a South Eastern European population.

PubMed

Toçi, Ervin; Burazeri, Genc; Sørensen, Kristine; Kamberi, Haxhi; Brand, Helmut

2015-06-01

Public health practice has come to increasing recognition of health promotion and the central role of knowledge, attitude, beliefs and practices in achieving health promotion. Health literacy (HL) is an under-explored topic in South Eastern European countries. There are no HL reports from Albania to date. The aim of this study was to assess the concurrent validity of the European Health Literacy Survey Questionnaire (HLS-EU-Q) and the Test of Functional Health Literacy in Adults (TOFHLA) in a population-based sample of adults in Albania. A cross-sectional study was conducted in 2013 in Tirana, Albania, including 239 individuals aged ≥ 18 years (61% women; 87% response). A structured interviewer-administered questionnaire was applied twice (test and retest procedure after 2 weeks) including HLS-EU-Q and TOFHLA instruments. The internal consistency was high for both instruments (Cronbach's alpha for the test procedure was 0.92 for TOFHLA and 0.98 for HLS-EU-Q). Both tools exhibited a high stability over time (Spearman's rho: 0.88 for TOFHLA and 0.87 for HLS-EU). Mean values of both instruments were similar in men and women (mean score for TOFHLA: 76.0 vs. 76.5, P = 0.83; mean score for HLS-EU-Q: 32.2 vs. 32.6, P = 0.63). For both instruments, higher HL scores were significantly associated with younger age, higher educational and economic level and lower body mass index. Our study provides valuable novel evidence on concurrent validation of two major HL instruments in a South Eastern European population-based sample. Future studies should be conducted in order to confirm and expand our findings. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Effect of various factors on ethanol yields from lignocellulosic biomass by Thermoanaerobacterium AK₁₇.

PubMed

Almarsdottir, Arnheidur Ran; Sigurbjornsdottir, Margret Audur; Orlygsson, Johann

2012-03-01

The ethanol production capacity from sugars and lignocellulosic biomass hydrolysates (HL) by Thermoanaerobacterium strain AK(17) was studied in batch cultures. The strain converts various carbohydrates to, acetate, ethanol, hydrogen, and carbon dioxide. Ethanol yields on glucose and xylose were 1.5 and 1.1 mol/mol sugars, respectively. Increased initial glucose concentration inhibited glucose degradation and end product formation leveled off at 30 mM concentrations. Ethanol production from 5 g L(-1) of complex biomass HL (grass, hemp, wheat straw, newspaper, and cellulose) (Whatman paper) pretreated with acid (0.50% H(2) SO(4)), base (0.50% NaOH), and without acid/base (control) and the enzymes Celluclast and Novozyme 188 (0.1 mL g(-1) dw; 70 and 25 U g(-1) of Celluclast and Novozyme 188, respectively) was investigated. Highest ethanol yields (43.0 mM) were obtained on cellulose but lowest on hemp leafs (3.6 mM). Chemical pretreatment increased ethanol yields substantially from lignocellulosic biomass but not from cellulose. The influence of various factors (HL, enzyme, and acid/alkaline concentrations) on end-product formation from 5 g L(-1) of grass and cellulose was further studied to optimize ethanol production. Highest ethanol yields (5.5 and 8.6 mM ethanol g(-1) grass and cellulose, respectively) were obtained at very low HL concentrations (2.5 g L(-1)); with 0.25% acid/alkali (v/v) and 0.1 mL g(-1) enzyme concentrations. Inhibitory effects of furfural and hydroxymethylfurfural during glucose fermentation, revealed a total inhibition in end product formation from glucose at 4 and 6 g L(-1), respectively. Copyright © 2011 Wiley Periodicals, Inc.

Identification of Pure-Tone Audiologic Thresholds for Pediatric Cochlear Implant Candidacy: A Systematic Review.

PubMed

de Kleijn, Jasper L; van Kalmthout, Ludwike W M; van der Vossen, Martijn J B; Vonck, Bernard M D; Topsakal, Vedat; Bruijnzeel, Hanneke

2018-05-24

Although current guidelines recommend cochlear implantation only for children with profound hearing impairment (HI) (>90 decibel [dB] hearing level [HL]), studies show that children with severe hearing impairment (>70-90 dB HL) could also benefit from cochlear implantation. To perform a systematic review to identify audiologic thresholds (in dB HL) that could serve as an audiologic candidacy criterion for pediatric cochlear implantation using 4 domains of speech and language development as independent outcome measures (speech production, speech perception, receptive language, and auditory performance). PubMed and Embase databases were searched up to June 28, 2017, to identify studies comparing speech and language development between children who were profoundly deaf using cochlear implants and children with severe hearing loss using hearing aids, because no studies are available directly comparing children with severe HI in both groups. If cochlear implant users with profound HI score better on speech and language tests than those with severe HI who use hearing aids, this outcome could support adjusting cochlear implantation candidacy criteria to lower audiologic thresholds. Literature search, screening, and article selection were performed using a predefined strategy. Article screening was executed independently by 4 authors in 2 pairs; consensus on article inclusion was reached by discussion between these 4 authors. This study is reported according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Title and abstract screening of 2822 articles resulted in selection of 130 articles for full-text review. Twenty-one studies were selected for critical appraisal, resulting in selection of 10 articles for data extraction. Two studies formulated audiologic thresholds (in dB HLs) at which children could qualify for cochlear implantation: (1) at 4-frequency pure-tone average (PTA) thresholds of 80 dB HL or greater based on speech perception and auditory performance subtests and (2) at PTA thresholds of 88 and 96 dB HL based on a speech perception subtest. In 8 of the 18 outcome measures, children with profound HI using cochlear implants performed similarly to children with severe HI using hearing aids. Better performance of cochlear implant users was shown with a picture-naming test and a speech perception in noise test. Owing to large heterogeneity in study population and selected tests, it was not possible to conduct a meta-analysis. Studies indicate that lower audiologic thresholds (≥80 dB HL) than are advised in current national and manufacturer guidelines would be appropriate as audiologic candidacy criteria for pediatric cochlear implantation.

Adrenal and liver in normal and cld/cld mice synthesize and secrete hepatic lipase, but the lipase is inactive in cld/cld mice.

PubMed

Schultz, C J; Blanchette-Mackie, E J; Scow, R O

2000-02-01

Combined lipase deficiency (cld) is a recessive mutation in mice that causes a severe lack of lipoprotein lipase (LPL) and hepatic lipase (HL) activities, hyperlipemia, and death within 3 days after birth. Earlier studies showed that inactive LPL and HL were synthesized by cld/cld tissues and that LPL synthesized by cld/cld brown adipocytes was retained in their ER. We report here a study of HL in liver, adrenal, and plasma of normal newborn and cld/cld mice. Immunofluorescence studies showed HL was present in extracellular space, but not in cells, in liver and adrenal of both normal and cld/cld mice. When protein secretion was blocked with monensin, HL was retained intracellularly in liver cell cultures and in incubated adrenal tissues of both groups of mice. These findings demonstrated that HL was synthesized and secreted by liver and adrenal cells in normal newborn and cld/cld mice. HL activities in liver, adrenal, and plasma in cld/cld mice were very low, <8% of that in normal newborn mice, indicating that HL synthesized and secreted by cld/cld cells was inactive. Livers of both normal newborn and cld/cld mice synthesized LPL, but the level of LPL activity in cld/cld liver was very low, <9% of that in normal liver. Immunofluorescence studies showed that LPL was present intracellularly in liver of cld/cld mice, indicating that LPL was synthesized but not secreted by cld/cld liver cells. Immunofluorescent LPL was not found in normal newborn liver cells unless the cells were treated with monensin, thus demonstrating that normal liver cells synthesized and secreted LPL. Livers of both groups of mice contained an unidentified alkaline lipase activity which accounted for 34-54% of alkaline lipase activity in normal and 65% of that in cld/cld livers. Our findings indicate that liver and adrenal cells synthesized and secreted HL in both normal newborn and cld/cld mice, but the lipase was inactive in cld/cld mice. That cld/cld liver cells secreted inactive HL while retaining inactive LPL indicates that these closely related lipases were processed differently.

Relationship between structure and antiproliferative activity of 1-azaflavanones.

PubMed

Kawaii, Satoru; Endo, Kotaro; Tokiwano, Tetsuo; Yoshizawa, Yuko

2012-07-01

The synthesis of 19 derivatives of 2-phenyl-3,4-dihydroquinolin-4(1H)-one, as aza analogs of flavanones, was carried out and these compounds were further screened for their antiproliferative activity toward HL60 promyelocytic leukemia cells. In comparison with flavanone the replacement of C-ring ether oxygen atom with a nitrogen atom potentiated activity by more than 100-fold. It was suggested that the aromaticity of the B-ring contributes greatly to the activity of 1-azaflavanones.

Health Literacy-Related Knowledge, Attitude, and Perceived Barriers: A Cross-sectional Study among Physicians, Pharmacists, and Nurses in Public Hospitals of Penang, Malaysia.

PubMed

Rajah, Retha; Hassali, Mohamed Azmi; Lim, Ching Jou

2017-01-01

Patients' health literacy (HL) has emerged as a critical determinant of health outcomes and becoming one of the core competencies of health-care providers. Therefore, this study aimed to assess among Malaysian physicians, pharmacists, and nurses, their HL-related knowledge, attitude, and perceived barriers, and also to determine the associated factors. A cross-sectional study design was used to enroll 600 eligible respondents using stratified sampling from 6 public hospitals in Penang, Malaysia. A validated self-administered questionnaire was used for data collection. Descriptive and inferential analysis was performed with statistical significance defined as p  < 0.05. The response rate was 87.6% with 526 questionnaires completed. Of these, 34.2% had poor knowledge, and more than half had negative attitude (51.9%) toward HL with no significant differences among physicians, pharmacists, and nurses. The majority of the respondents perceived time constraints and lack of human resources as major HL barriers. Respondents who had heard the term or concept of HL had significantly higher level of knowledge ( p  < 0.001) and more positive attitude ( p  < 0.001). While longer service years (≥11 years) significantly contribute to the higher level of HL knowledge among health-care providers ( p  = 0.028). The study findings supported the concern on inadequate knowledge and substantially negative attitude toward HL among study health-care providers with highest cited barriers were time constraint and human resources. Thus, efforts to improve their perspective about HL to be effective patient educators are highly advocated.

Tick vitellogenin receptor reveals critical role in oocyte development and transovarial transmission of Babesia parasite.

PubMed

Boldbaatar, Damdinsuren; Battsetseg, Badgar; Matsuo, Tomohide; Hatta, Takeshi; Umemiya-Shirafuji, Rika; Xuan, Xuenan; Fujisaki, Kozo

2008-08-01

A cDNA encoding the vitellogenin receptor of the ixodid tick, Haemaphysalis longicornis Neumann (HlVgR) was cloned and characterized. The full-length cDNA is 5631 bp, including an intact ORF encoding an expected protein with 1782 amino acids. The deduced amino acid sequence of the HlVgR cDNA revealed two ligand-binding domains with four class A cysteine-rich repeats in the first domain and eight in the second domain similar to those of insect VgRs. The immunoblot analysis detected approximately 197 kDa protein in both tick ovary and egg. The developmental expression profile demonstrated that HlVgR mRNA exists throughout the ovarian development, and the transcriptional level is especially high in the previtellogenic period. Immuno electron microscopy analysis demonstrated that the localization of HlVgR is detected on the external surface of oocyte plasma membrane. RNAi showed that eggs of HlVgR dsRNA-injected adult ticks had not developed into fully mature oocytes and laid abnormal eggs. The Babesia parasite DNA was not detected in the eggs of HlVgR dsRNA-injected tick that fed on Babesia gibsoni infected dog, whereas it was detected in the eggs of PBS-injected ticks and noninjected ticks. Expression of HlVgR was increased by the vitellogenic hormone 20-hydroxyecdysone. These results indicate that HlVgR, which is produced by the developing oocytes, is essential for Vg uptake, egg development in the H. longicornis tick, and transovarial transmission of Babesia parasites.

Complex Immune Evasion Strategies in Classical Hodgkin Lymphoma.

PubMed

Wein, Frederik; Weniger, Marc A; Höing, Benedikt; Arnolds, Judith; Hüttmann, Andreas; Hansmann, Martin-Leo; Hartmann, Sylvia; Küppers, Ralf

2017-12-01

The cellular microenvironment in classical Hodgkin lymphoma (cHL) is dominated by a mixed infiltrate of inflammatory cells with typically only about 1% Hodgkin and Reed/Sternberg (HRS) tumor cells. T cells are usually the largest population of cells in the cHL microenvironment, encompassing T helper (Th) cells, regulatory T cells (Tregs), and cytotoxic T cells. Th cells and Tregs presumably provide essential survival signals for HRS cells. Tregs are also involved in rescuing HRS cells from antitumor immune responses. An understanding of the immune evasion strategies of HRS cells is not only relevant for a characterization of the pathophysiology of cHL but is also clinically relevant, given the current treatment approaches targeting checkpoint inhibitors. Here, we characterized the cHL-specific CD4 + T-cell infiltrate regarding its role in immune evasion. Global gene expression analysis of CD4 + Th cells and Tregs isolated from cHL lymph nodes and reactive tonsils revealed that Treg signatures were enriched in CD4 + Th cells of cHL. Hence, HRS cells may induce Treg differentiation in Th cells, a conclusion supported by in vitro studies with Th cells and cHL cell lines. We also found evidence for immune-suppressive purinergic signaling and a role of the inhibitory receptor-ligand pairs B- and T-cell lymphocyte attenuator-herpesvirus entry mediator and CD200R-CD200 in promoting immune evasion. Taken together, this study highlights the relevance of Treg induction and reveals new immune checkpoint-driven immune evasion strategies in cHL. Cancer Immunol Res; 5(12); 1122-32. ©2017 AACR . ©2017 American Association for Cancer Research.

Synthesis and characterization of Cu(II), Co(II) and Ni(II) complexes of a number of sulfadrug azodyes and their application for wastewater treatment

NASA Astrophysics Data System (ADS)

El-Baradie, K.; El-Sharkawy, R.; El-Ghamry, H.; Sakai, K.

2014-03-01

The azodye ligand (HL1) was synthesized from the coupling of sulfaguanidine diazonium salt with 2,4-dihydroxy-benzaldehyde while the two ligands, HL2 and HL3, were prepared by the coupling of sulfadiazine diazonium salt with salicylaldehyde (HL2) and 2,4-dihydroxy-benzaldehyde (HL3). The prepared ligands were characterized by elemental analysis, IR, 1H NMR and mass spectra. Cu(II), Co(II) and Ni(II) complexes of the prepared ligands have been synthesized and characterized by various spectroscopic techniques like IR, UV-Visible as well as magnetic and thermal (TG and DTA) measurements. It was found that all the ligands behave as a monobasic bidentate which coordinated to the metal center through the azo nitrogen and α-hydroxy oxygen atoms in the case of HL1 and HL3. HL2 coordinated to the metal center through sulfonamide oxygen and pyrimidine nitrogen. The applications of the prepared complexes in the oxidative degradation of indigo carmine dye exhibited good catalytic activity in the presence of H2O2 as an oxidant. The reactions followed first-order kinetics and the rate constants were determined. The degradation reaction involved the catalytic action of the azo-dye complexes toward H2O2 decomposition, which can lead to the generation of HOrad radicals as a highly efficient oxidant attacking the target dye. The detailed kinetic studies and the mechanism of these catalytic reactions are under consideration in our group.

Hepatic lipidosis: Clinical review drawn from collective effort.

PubMed

Webb, Craig B

2018-03-01

Practical relevance: Hepatic lipidosis (HL) is the most common form of liver dysfunction in cats. If recognized early and treated appropriately, the prognosis is good; if not, the prognosis is grave. Clinical challenges: Distinguishing HL as idiopathic or secondary is critical since the presence of a concurrent disease affects the therapeutic plan and the prognosis. Despite the unique and severe nature of a cat's response to anorexia and the complexity of the metabolic changes underlying this condition, the clinical acumen and technical ability to effectively diagnose and treat HL are readily available to all small animal practitioners. Patient group: Although many species develop a 'fatty liver', the cat is one of relatively few species that suffer from HL. The classic presentation is that of an overweight cat that stops eating for days to weeks, losing weight in the process. Equipment: Abdominal ultrasound is frequently employed in the diagnostic work-up of an anorectic cat; ultrasonographic findings often support a presumptive diagnosis, provide samples for cytology and, perhaps most importantly, help identify concurrent conditions that must be addressed for therapeutic success. All of the equipment necessary for essential nutritional intervention in an anorectic cat is readily available and easily affordable. Evidence base: The material for this review draws heavily on a relatively large number of original studies, excellent reviews by recognized experts, and informative communication with experienced clinicians, hence the term 'collective effort'.

Semantic interoperability--HL7 Version 3 compared to advanced architecture standards.

PubMed

Blobel, B G M E; Engel, K; Pharow, P

2006-01-01

To meet the challenge for high quality and efficient care, highly specialized and distributed healthcare establishments have to communicate and co-operate in a semantically interoperable way. Information and communication technology must be open, flexible, scalable, knowledge-based and service-oriented as well as secure and safe. For enabling semantic interoperability, a unified process for defining and implementing the architecture, i.e. structure and functions of the cooperating systems' components, as well as the approach for knowledge representation, i.e. the used information and its interpretation, algorithms, etc. have to be defined in a harmonized way. Deploying the Generic Component Model, systems and their components, underlying concepts and applied constraints must be formally modeled, strictly separating platform-independent from platform-specific models. As HL7 Version 3 claims to represent the most successful standard for semantic interoperability, HL7 has been analyzed regarding the requirements for model-driven, service-oriented design of semantic interoperable information systems, thereby moving from a communication to an architecture paradigm. The approach is compared with advanced architectural approaches for information systems such as OMG's CORBA 3 or EHR systems such as GEHR/openEHR and CEN EN 13606 Electronic Health Record Communication. HL7 Version 3 is maturing towards an architectural approach for semantic interoperability. Despite current differences, there is a close collaboration between the teams involved guaranteeing a convergence between competing approaches.

Photosynthetic conversion of CO2 to farnesyl diphosphate-derived phytochemicals (amorpha-4,11-diene and squalene) by engineered cyanobacteria.

PubMed

Choi, Sun Young; Lee, Hyun Jeong; Choi, Jaeyeon; Kim, Jiye; Sim, Sang Jun; Um, Youngsoon; Kim, Yunje; Lee, Taek Soon; Keasling, Jay D; Woo, Han Min

2016-01-01

Metabolic engineering of cyanobacteria has enabled photosynthetic conversion of CO2 to value-added chemicals as bio-solar cell factories. However, the production levels of isoprenoids in engineered cyanobacteria were quite low, compared to other microbial hosts. Therefore, modular optimization of multiple gene expressions for metabolic engineering of cyanobacteria is required for the production of farnesyl diphosphate-derived isoprenoids from CO2. Here, we engineered Synechococcus elongatus PCC 7942 with modular metabolic pathways consisting of the methylerythritol phosphate pathway enzymes and the amorphadiene synthase for production of amorpha-4,11-diene, resulting in significantly increased levels (23-fold) of amorpha-4,11-diene (19.8 mg/L) in the best strain relative to a parental strain. Replacing amorphadiene synthase with squalene synthase led to the synthesis of a high amount of squalene (4.98 mg/L/OD730). Overexpression of farnesyl diphosphate synthase is the most critical factor for the significant production, whereas overexpression of 1-deoxy-d-xylulose 5-phosphate reductase is detrimental to the cell growth and the production. Additionally, the cyanobacterial growth inhibition was alleviated by expressing a terpene synthase in S. elongatus PCC 7942 strain with the optimized MEP pathway only (SeHL33). This is the first demonstration of photosynthetic production of amorpha-4,11-diene from CO2 in cyanobacteria and production of squalene in S. elongatus PCC 7942. Our optimized modular OverMEP strain (SeHL33) with either co-expression of ADS or SQS demonstrated the highest production levels of amorpha-4,11-diene and squalene, which could expand the list of farnesyl diphosphate-derived isoprenoids from CO2 as bio-solar cell factories.

Chronic liver injury promotes hepatocarcinoma cells seeding and growth, associated with the infiltration by macrophages.

PubMed

Delire, Bénédicte; Henriet, Patrick; Lemoine, Pascale; Leclercq, Isabelle A; Stärkel, Peter

2018-05-04

Ninety percent of hepatocarcinoma (HCC) develop in a chronically damaged liver. The interactions between non tumor stromal components, especially macrophages, and the cancer cells are still incompletely understood. Our aim was to determine whether a chronically injured liver represents a favorable environment for the seeding and growth of HCC cells, and to evaluate the potential roles of macrophages infiltrated within the tumor. HCC cells were injected into the liver in healthy mice (healthy liver group-HL) and in mice chronically treated with CCl 4 for 7 weeks (CCl 4 7w group). Livers were examined for the presence of tumor 2 weeks post injection. Tumor and non tumor tissues were analyzed for macrophages infiltration, origin (monocytes-derived vs resident macrophages) and polarization state, and matrix metalloproteinases (MMPs) production. Fifty-three percent of mice developed neoplastic lesion in the HL group while a tumor lesion was found in all livers in the CCl 4 7w group. Macrophages infiltrated more deeply the tumors of the CCl 4 7weeks group. Evaluation of factors involved in the recruitment of macrophages and of markers of their polarization state was in favor of prominent infiltration of M2 pro-tumor monocytes-derived macrophages inside the tumors developing in a chronically injured liver. MMP-2 and -9 production, attributed to M2 pro-tumor macrophages, was significantly higher in the tumors of the CCl 4 7w group. Chronic liver damage promotes cancer development in our model. Our results suggest that an injured background favors the infiltration of M2 pro-tumor monocytes-derived macrophages. These secrete MMP-2 and MMP-9 that promote tumor progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Community of Practice and Family Language Policy: Maintaining Heritage Japanese in Sydney--Ten Years Later

ERIC Educational Resources Information Center

Oriyama, Kaya

2016-01-01

Maintaining children's heritage language (HL) is a challenging task for linguistic minorities around the world. While many Japanese heritage children in Sydney attend weekend HL schools, they typically discontinue attendance before, or during, secondary school. To date, no longitudinal study has investigated what happens to their HL maintenance…

Differentiating Heritage and Foreign Language Learners of Spanish: Needs, Perceptions, and Expectations

ERIC Educational Resources Information Center

Hedgcock, John S.; Lefkowitz, Natalie

2016-01-01

Research on heritage language (HL) development and education has characterized the unique linguistic, sociocultural, and affective profiles of heritage-language (HL) students, yet foreign-language (FL) education has only begun to understand HL students in relation to non-heritage students (Carreira & Kagan, 2011; Felix, 2008). To deepen our…

Transactional Associations between Supportive Family Climate and Young Children's Heritage Language Proficiency in Immigrant Families

ERIC Educational Resources Information Center

Park, Heejung; Tsai, Kim M.; Liu, Lisa L.; Lau, Anna S.

2012-01-01

Heritage language (HL) proficiency confers developmental benefits; however, the onset of HL loss is observed among many young children from immigrant families. In this longitudinal study, transactional associations between children's HL proficiency and supportive family climate were examined in Chinese immigrant families with pre-school-aged…

Health literacy and asthma.

PubMed

Rosas-Salazar, Christian; Apter, Andrea J; Canino, Glorisa; Celedón, Juan C

2012-04-01

The report "Healthy people" from the US Department of Health and Human Services defines health literacy (HL) as follows: "The degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions." The same report identifies asthma as a public health problem of high priority. Unfortunately, impaired HL is prevalent in our society, and patients with low HL and asthma face multiple challenges as they attempt to manage their disease. Indeed, the National Asthma Education and Prevention Program's current guidelines require patients to have considerable HL and self-management skills. Numerous studies have linked inadequate literacy with poor health outcomes. Unlike many sociodemographic variables, HL can potentially be addressed in the health care setting. The purpose of this review is to raise awareness of the problem, summarize the current evidence linking HL and asthma, and offer strategies to strengthen the communication between patients and health care providers to decrease asthma health disparities. In addition, we discuss potential future directions for research in this field. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

A polysaccharide from the fruiting bodies of Agaricus blazei Murill induces caspase-dependent apoptosis in human leukemia HL-60 cells.

PubMed

Li, Xiaohui; Zhao, Xin; Wang, Hongmin; Han, Junqing; Liu, Li

2014-09-01

Polysaccharides are the major active ingredients of fungus Agaricus blazei for treating and preventing cancer. However, there are no reports showing anti-tumor activity of A. blazei polysaccharides (ABP) on human leukemia (HL)-60 cells in vitro and in vivo. In this study, we demonstrated that ABP efficiently inhibited proliferation of cultured HL-60 cells, which was associated with the induction of apoptosis. The increase in ABP-induced apoptosis was accompanied by loss of mitochondria membrane potential (∆Ψm), cytochrome c release from the mitochondria, activation of caspase-3, degradation of poly(ADP-ribose) polymerase (PARP), and the elevated ratio of Bcl-2-associated X (Bax)/B-cell lymphoma 2 (Bcl-2). Moreover, z-DEVD-fmk, a caspase-3 inhibitor, reversed the cytotoxic effects and apoptotic characteristics induced by ABP in HL-60 cells. Furthermore, we confirmed that ABP could obviously inhibit the solid cancer growth of leukemia HL-60 in tumor xenograft model. These data demonstrated that ABP effectively induced the apoptosis of HL-60 cells via a signaling cascade of mitochondrial caspase-3-dependent pathway.

Cytarabine-resistant leukemia cells are moderately sensitive to clofarabine in vitro.

PubMed

Yamauchi, Takahiro; Uzui, Kanako; Nishi, Rie; Shigemi, Hiroko; Ueda, Takanori

2014-04-01

Clofarabine is transported into leukemic cells via the equilibrative nucleoside transporters (hENT) 1 and 2 and the concentrative nucleoside transporter (hCNT) 3, then phosphorylated by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) to an active triphosphate metabolite. Cytarabine uses hENT1 and dCK for its activation. We hypothesized that cytarabine-resistant leukemia cells retain sensitivity to clofarabine. Human myeloid leukemia HL-60 cells and cytarabine-resistant variant HL/ara-C20 cells were used in the present study. Despite 20-fold cytarabine resistance, the HL/ara-C20 cells exhibited only a 6-fold resistance to clofarabine compared to HL-60 cells. The intracellular concentration of the triphosphate metabolite of cytarabine was reduced to 1/10, and that of clofarabine was halved in the HL/ara-C20 cells. hENT1 and dCK were reduced, but hCNT3 and dGK were not altered in the HL/ara-C20 cells, which might contribute to their retained capability to produce intracellular triphosphate metabolite of clofarabine. Clofarabine was cytotoxic to leukemia cells that were resistant to cytarabine.

[Studies on red orpiment induction of NB4 and HL-60 cell apoptosis].

PubMed

Bai, Y; Huang, S

1998-09-01

To study the possible mechanism of red orpiment, which is main component of composite indigo naturalis tablets, in the treatment of acute promyelocytic leukemia(APL). The effect of red orpiment on induction of APL cell line NB4 and HL-60 apoptosis were studied by cell morphology, DNA gel electrophoresis and flow cytometry assay. Red orpiment induced NB4 and HL-60 cell apoptosis. When treated with different concentration of red orpiment(25-200 micrograms/ml) for 16 hours, both NB4 and HL-60 cells showed typical apoptosis features. If decreased the concentration of red orpiment to 12.5 micrograms/ml, the NB4 cell still showed apoptosis features while the HL-60 cell did not when cultured for 72 hours. Arsenic disulfide(As2S2) had the same effect as red orpiment did under the same experiment condition. It is the main component, As2S2 of the red orpiment that can induces NB4 and HL-60 cell apoptosis. and the red orpiment is responsible for the high CR rate of APL induced by the composite indigo naturalis tablets.

Deriving flow directions for coarse-resolution (1-4 km) gridded hydrologic modeling

NASA Astrophysics Data System (ADS)

Reed, Seann M.

2003-09-01

The National Weather Service Hydrology Laboratory (NWS-HL) is currently testing a grid-based distributed hydrologic model at a resolution (4 km) commensurate with operational, radar-based precipitation products. To implement distributed routing algorithms in this framework, a flow direction must be assigned to each model cell. A new algorithm, referred to as cell outlet tracing with an area threshold (COTAT) has been developed to automatically, accurately, and efficiently assign flow directions to any coarse-resolution grid cells using information from any higher-resolution digital elevation model. Although similar to previously published algorithms, this approach offers some advantages. Use of an area threshold allows more control over the tendency for producing diagonal flow directions. Analyses of results at different output resolutions ranging from 300 m to 4000 m indicate that it is possible to choose an area threshold that will produce minimal differences in average network flow lengths across this range of scales. Flow direction grids at a 4 km resolution have been produced for the conterminous United States.

Beta-mangostin from Cratoxylum arborescens activates the intrinsic apoptosis pathway through reactive oxygen species with downregulation of the HSP70 gene in the HL60 cells associated with a G0/G1 cell-cycle arrest.

PubMed

Omer, Fatima Abdelmutaal Ahmed; Hashim, Najihah Binti Mohd; Ibrahim, Mohamed Yousif; Dehghan, Firouzeh; Yahayu, Maizatulakmal; Karimian, Hamed; Salim, Landa Zeenelabdin Ali; Mohan, Syam

2017-11-01

Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G 0 /G 1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G 0 /G 1 phase and prompted the intrinsic apoptosis pathway.

Measuring attributes of health literate health care organizations from the patients' perspective: Development and validation of a questionnaire to assess health literacy-sensitive communication (HL-COM).

PubMed

Ernstmann, Nicole; Halbach, Sarah; Kowalski, Christoph; Pfaff, Holger; Ansmann, Lena

2017-04-01

Studies addressing the organizational contexts of care that may help increase the patients' ability to cope with a disease and to navigate through the health care system are still rare. Especially instruments allowing the assessment of such organizational efforts from the patients' perspective are missing. The aim of our study was to develop a survey instrument assessing organizational health literacy (HL) from the patients' perspective, i. e., health care organizations' responsiveness to patients' individual needs. A pool of 30 items was developed by a group of experts based on a literature review. The items were developed, tested and prioritized according to their importance in 11 semi-structured interviews and cognitive think-aloud interviews with cancer patients. The resulting 16 items were rated in a standardized postal survey involving a total of N=453 colon and breast cancer patients treated in cancer centers in Germany. An exploratory factor analysis, a confirmatory factor analysis and structural equation modelling were conducted. Item properties were analyzed. 83.2 % of the patients were diagnosed with breast cancer, 16.8 % had a diagnosis of colon cancer. The patients' mean age was 61 (26-88), 89.4 % were female. The most common comorbidities were hypertension (34.0 %) and cardiovascular disease (11.0 %). The final prediction model included nine items measuring the degree of health literacy-sensitivity of communication. The model showed an acceptable model fit. The nine items showed corrected item-total correlations between .622 and .762 and item difficulties between 0.77 and 0.87. Cronbach's α was .912. In a comprehensive development process, the original item pool comprising several aspects of organizational HL was reduced to a one-dimensional scale. The instrument measures an important aspect of organizational HL; i.e., the degree of health literacy-sensitivity of communication (HL-COM). HL-COM was found to impact patient enablement, mediated through the support by physicians. Future research will have to test these associations in the context of other diseases or institutions. Copyright © 2017. Published by Elsevier GmbH.

Elevated Serum Levels of sCD30 and IL6 and Detectable IL10 Precede Classical Hodgkin Lymphoma Diagnosis.

PubMed

Levin, Lynn I; Breen, Elizabeth C; Birmann, Brenda M; Batista, Julie L; Magpantay, Larry I; Li, Yuanzhang; Ambinder, Richard F; Mueller, Nancy E; Martínez-Maza, Otoniel

2017-07-01

Background: We investigated whether an immune system environment characterized by elevated serum levels of B-cell activation molecules was associated with the subsequent development of classical Hodgkin lymphoma (cHL). Methods: We measured serum levels of B-cell-stimulatory cytokines, IL6 and IL10, soluble CD30 (sCD30), and total IgE prior to cHL diagnosis in 103 cases and 206 matched controls with archived specimens in the DoD Serum Repository. Results: Prediagnosis serum sCD30 and IL6 levels had strong positive associations with risk of a cHL diagnosis 0 to 1 year prior to diagnosis [sCD30 OR = 5.5; 95% confidence interval (CI), 3.4-9.0; IL6 OR = 4.6; 95% CI, 2.9-7.5] and >1 year to 2 years pre-cHL diagnosis (sCD30 OR = 3.3; 95% CI, 1.6-6.7; IL6 OR = 2.9; 95% CI, 1.3-6.5). We observed similar, albeit not consistently significant positive associations, over 4 or more years preceding diagnosis. We did not observe a clear association with IgE levels. Of note, detectable IL10 levels were significantly associated with Epstein-Barr virus (EBV)-positive cHL cases compared with EBV-negative cases. Conclusion: In this prospective analysis, elevated sCD30 and IL6 levels and detectable IL10 preceded cHL diagnosis. Impact: The associations of these cytokines with cHL risk may reflect the production of these molecules by proliferating nascent cHL tumor cells, or by immune cells responding to their presence, prior to clinical detection. The stable elevation in cHL risk, 4 or more years prediagnosis, also suggests that a B-cell-stimulatory immune system milieu precedes, and may promote, lymphomagenesis. Cancer Epidemiol Biomarkers Prev; 26(7); 1114-23. ©2017 AACR . ©2017 American Association for Cancer Research.

In vitro assessment of oxidative stress and apoptotic mechanisms of garlic extract in the treatment of acute promyelocytic leukemia

PubMed Central

Yedjou, Clement G.; Tchounwou, Paul B.

2012-01-01

Introduction Garlic supplementation in diet has been shown to be beneficial to cancer patients. Recently, its pharmacological role in the prevention and treatment of cancer has received increasing attention. However, the mechanisms by which garlic extract (GE) induces cytotoxicity, oxidative stress, and apoptosis in cancer cells remain largely unknown. Objective The present study was designed to use HL-60 cells as a test model to evaluate whether or not GE-induced cytotoxicty and apoptosis in human leukemia (HL-60) cells is mediated through oxidative stress. Methods Human leukemia (HL-60) cells were treated with different concentrations of GE for 12 hr. Cell survival was determined by MTT assay. The extent of oxidative cell/tissue damage was determined by measuring malondialdehyde (lipid peroxidation biomarker) concentrations by spectrophotometry. Cell apoptosis was measured by flow cytometry assessment (Annexin-V and caspase-3 assays) and agarose gel electrophoresis (DNA laddering assay). Results Data obtained from the MTT assay indicated that GE significantly (p < 0.05) reduced the viability of HL-60 cells in a concentration-dependent manner. We detected a significant (p < 0.05) increase in malondialdehyde (MDA) concentrations in GE-treated HL-60 cells compared to the control. Flow cytometry data showed a strong concentration-response relationship between GE exposure and Annexin-V positive HL-60 cells. Similarly, a statistically significant and concentration-dependent increase (p <0.05) were recorded with regard to caspase-3 activity in HL-60 cells undergoing late apoptosis. These results were confirmed by data of DNA laddering assay showing a clear evidence of nucleosomal DNA fragmentation in GE-treated cells. Conclusion Our finding indicates that GE-induced cytotoxicity and apoptosis in HL-60 cells involve phosphatidylserine externalization, caspase-3 activation, and nucleosomal DNA fragmentation associated with the formation of MDA, a by-product of lipid peroxidation and biomarker of oxidative stress. At therapeutic concentrations, GE-induced cytotoxic and apoptotic effects in HL-60 cells is mediated by oxidative stress. PMID:23847719

Effects of Health Level 7 Messaging on Data Quality in New York City's Immunization Information System, 2014.

PubMed

Metroka, Amy E; Papadouka, Vikki; Ternier, Alexandra; Zucker, Jane R

2016-01-01

We compared the quality of data reported to New York City's immunization information system, the Citywide Immunization Registry (CIR), through its real-time Health Level 7 (HL7) Web service from electronic health records (EHRs), with data submitted through other methods. We stratified immunizations administered and reported to the CIR in 2014 for patients aged 0-18 years by reporting method: (1) sending HL7 messages from EHRs through the Web service, (2) manual data entry, and (3) upload of a non-standard flat file from EHRs. We assessed completeness of reporting by measuring the percentage of immunizations reported with lot number, manufacturer, and Vaccines for Children (VFC) program eligibility. We assessed timeliness of reporting by determining the number of days from date of administration to date entered into the CIR. HL7 reporting accounted for the largest percentage (46.3%) of the 3.8 million immunizations reported in 2014. Of immunizations reported using HL7, 97.9% included the lot number and 92.6% included the manufacturer, compared with 50.4% and 48.0% for manual entry, and 65.9% and 48.8% for non-standard flat file, respectively. VFC eligibility was 96.9% complete when reported by manual data entry, 95.3% complete for HL7 reporting, and 87.2% complete for non-standard flat file reporting. Of the three reporting methods, HL7 was the most timely: 77.6% of immunizations were reported by HL7 in <1 day, compared with 53.6% of immunizations reported through manual data entry and 18.1% of immunizations reported through non-standard flat file. HL7 reporting from EHRs resulted in more complete and timely data in the CIR compared with other reporting methods. Providing resources to facilitate HL7 reporting from EHRs to immunization information systems to increase data quality should be a priority for public health.

Effects of Health Level 7 Messaging on Data Quality in New York City's Immunization Information System, 2014

PubMed Central

Papadouka, Vikki; Ternier, Alexandra; Zucker, Jane R.

2016-01-01

Objective We compared the quality of data reported to New York City's immunization information system, the Citywide Immunization Registry (CIR), through its real-time Health Level 7 (HL7) Web service from electronic health records (EHRs), with data submitted through other methods. Methods We stratified immunizations administered and reported to the CIR in 2014 for patients aged 0–18 years by reporting method: (1) sending HL7 messages from EHRs through the Web service, (2) manual data entry, and (3) upload of a non-standard flat file from EHRs. We assessed completeness of reporting by measuring the percentage of immunizations reported with lot number, manufacturer, and Vaccines for Children (VFC) program eligibility. We assessed timeliness of reporting by determining the number of days from date of administration to date entered into the CIR. Results HL7 reporting accounted for the largest percentage (46.3%) of the 3.8 million immunizations reported in 2014. Of immunizations reported using HL7, 97.9% included the lot number and 92.6% included the manufacturer, compared with 50.4% and 48.0% for manual entry, and 65.9% and 48.8% for non-standard flat file, respectively. VFC eligibility was 96.9% complete when reported by manual data entry, 95.3% complete for HL7 reporting, and 87.2% complete for non-standard flat file reporting. Of the three reporting methods, HL7 was the most timely: 77.6% of immunizations were reported by HL7 in <1 day, compared with 53.6% of immunizations reported through manual data entry and 18.1% of immunizations reported through non-standard flat file. Conclusion HL7 reporting from EHRs resulted in more complete and timely data in the CIR compared with other reporting methods. Providing resources to facilitate HL7 reporting from EHRs to immunization information systems to increase data quality should be a priority for public health. PMID:27453603

Glue Ear, Hearing Loss and IQ: An Association Moderated by the Child’s Home Environment

PubMed Central

Hall, Amanda J.; Maw, Richard; Midgley, Elizabeth; Golding, Jean; Steer, Colin

2014-01-01

Background Glue ear or otitis media with effusion (OME) is common in children and may be associated with hearing loss (HL). For most children it has no long lasting effects on cognitive development but it is unclear whether there are subgroups at higher risk of sequelae. Objectives To examine the association between a score comprising the number of times a child had OME and HL (OME/HL score) in the first four/five years of life and IQ at age 4 and 8. To examine whether any association between OME/HL and IQ is moderated by socioeconomic, child or family factors. Methods Prospective, longitudinal cohort study: the Avon Longitudinal Study of Parents and Children (ALSPAC). 1155 children tested using tympanometry on up to nine occasions and hearing for speech (word recognition) on up to three occasions between age 8 months and 5 years. An OME/HL score was created and associations with IQ at ages 4 and 8 were examined. Potential moderators included a measure of the child’s cognitive stimulation at home (HOME score). Results For the whole sample at age 4 the group with the highest 10% OME/HL scores had performance IQ 5 points lower [95% CI −9, −1] and verbal IQ 6 points lower [95% CI −10, −3] than the unaffected group. By age 8 the evidence for group differences was weak. There were significant interactions between OME/HL and the HOME score: those with high OME/HL scores and low 18 month HOME scores had lower IQ at age 4 and 8 than those with high OME/HL scores and high HOME scores. Adjusted mean differences ranged from 5 to 8 IQ points at age 4 and 8. Conclusions The cognitive development of children from homes with lower levels of cognitive stimulation is susceptible to the effects of glue ear and hearing loss. PMID:24498289

Polymerization of a dual-cured cement through ceramic: LED curing light vs halogen lamp.

PubMed

Lopes, Lawrence Gonzaga; Franco, Eduardo Batista; Name Neto, Abrão; Herrera, Francyle S; Kurachi, Cristina; Castañeda-Espinosa, Juan C; Lauris, José Roberto Pereira

2004-12-01

The aim of this study was to investigate the influence of light source, LED unit and halogen lamp (HL), on the effectiveness of Enforce dual-cured cement cured under a ceramic disc. Three exposure times (60, 80 and 120 s) were also evaluated. Two experimental groups, in which the polymerization of the dual-cured cement was performed through a ceramic disc, and two control groups, in which the polymerization of the dual-cured cement was performed directly without presence of ceramic disc were subdivided into three subgroups (three different exposure times), with five specimens each: G1A- HL 60s; G1B- HL 80s; G1C- HL 120s; G2A- LED 60s; G2B- LED 80s; G2C- LED 120s; and control groups: G3A- HL 60s; G3B- HL 80s; G3C- HL 120s; G4A- LED 60s; G4B- LED 80s and G4C- LED 120s. Cement was applied in a steel matrix (4mm diameter, 1.2mm thickness). In the experimental groups, a ceramic disc was placed on top. The cement was light-cured through the ceramic by a HL and LED, however, the control groups were cured without the ceramic disc. The specimens were stored in a light-proof container at 37ºC for 24 hours, then Vickers hardness was determined. A four-way ANOVA and Tukey test (p£ 0.05) were performed. All specimens cured by LED for 60s showed inferior values compared with the halogen groups. In general, light-curing by LED for 80s and 120s was comparable to halogen groups (60s and 80s) and their control groups. LED technology can be viable for light-curing through conventional ceramic indirect restorations, when curing time is increased in relation to HL curing time.

HL-10 on lakebed

NASA Technical Reports Server (NTRS)

1968-01-01

The HL-10 Lifting Body is seen here parked on Rogers Dry Lake, the unique location where it landed after research flights. This 1968 photo shows the vehicle after the fins were modified to remove instabilities encountered on the first flight. It involved a change to the shape of the leading edge of the fins to eliminate flow separation. It required extensive wind-tunnel testing at Langley Research Center, Hampton, Va. NASA Flight Research Center (FRC) engineer Bob Kempel than plotted thousands of data points by hand to come up with the modification, which involved a fiberglass glove backed with a metal structure on each fin's leading edge. This transformed the vehicle from a craft that was difficult to control into the best handling of the original group of lifting bodies at the FRC. The HL-10 was one of five heavyweight lifting-body designs flown at NASA's Flight Research Center (FRC--later Dryden Flight Research Center), Edwards, California, from July 1966 to November 1975 to study and validate the concept of safely maneuvering and landing a low lift-over-drag vehicle designed for reentry from space. Northrop Corporation built the HL-10 and M2-F2, the first two of the fleet of 'heavy' lifting bodies flown by the NASA Flight Research Center. The contract for construction of the HL-10 and the M2-F2 was $1.8 million. 'HL' stands for horizontal landing, and '10' refers to the tenth design studied by engineers at NASA's Langley Research Center, Hampton, Va. After delivery to NASA in January 1966, the HL-10 made its first flight on Dec. 22, 1966, with research pilot Bruce Peterson in the cockpit. Although an XLR-11 rocket engine was installed in the vehicle, the first 11 drop flights from the B-52 launch aircraft were powerless glide flights to assess handling qualities, stability, and control. In the end, the HL-10 was judged to be the best handling of the three original heavy-weight lifting bodies (M2-F2/F3, HL-10, X-24A). The HL-10 was flown 37 times during the lifting body research program and logged the highest altitude and fastest speed in the Lifting Body program. On Feb. 18, 1970, Air Force test pilot Peter Hoag piloted the HL-10 to Mach 1.86 (1,228 mph). Nine days later, NASA pilot Bill Dana flew the vehicle to 90,030 feet, which became the highest altitude reached in the program. Some new and different lessons were learned through the successful flight testing of the HL-10. These lessons, when combined with information from it's sister ship, the M2-F2/F3, provided an excellent starting point for designers of future entry vehicles, including the Space Shuttle.

Assessing Auditory Processing Deficits in Tinnitus and Hearing Impaired Patients with the Auditory Behavior Questionnaire

PubMed Central

Diges, Isabel; Simón, Francisco; Cobo, Pedro

2017-01-01

Background and Purpose: Auditory processing disorders (APD), tinnitus and hearing loss (HL) are typical issues reported by patients in audiologic clinics. These auditory impairments can be concomitant or mutually excluding. APD are not necessarily accompanied by significant HL, whereas many adults exhibit peripheral HL and typical cognitive deficits often associated with APD. Since HL, tinnitus and APD affects to several parts of the ascending auditory pathway from the periphery to the auditory cortex, there could be some interrelationship between them. For instance, tinnitus has been reported to degrade the auditory localization capacity. Tinnitus is believed to be triggered by deafferentation of normal peripheral input to the central auditory system. This peripheral deficit can be accompanied by HL or not, since a type of permanent cochlear damage (thus deafferentation) without an elevation of hearing thresholds might persist. Therefore, a combined study of APD, tinnitus and HL on the same cohort of patients can be audiologically relevant and worthy. Methods: Statistical analysis is applied to a cohort of 305 patients attending an audiology clinic in Madrid (Spain). This group of patients is first categorized in four subgroups, namely, HLTG (with tinnitus and HL), NHLTG (with tinnitus and without HL), HLNTG (with HL but no tinnitus), and NHLNTG (neither tinnitus nor HL). The statistical variables include Age, Average Auditory Threshold (ATT), for assessing HL, Tinnitus Handicap Inventory (THI), for measuring tinnitus, and a new 25-item Auditory Behavior Questionnaire (ABQ), for scoring APD. Factor analysis is applied to arrange these items into 4 subscales. The internal consistency reliability of this ABQ is confirmed by calculating Cronbach's coefficients α. The test-retest reliability is assessed by the intraclass correlation coefficients, ICC. Statistical techniques applied to the data set include descriptive analysis of variables and Spearman rank correlations (ρ) between them. Results: Overall reliability of ABQ is confirmed by an α value of 0.89 and by an ICC of 0.91. Regarding the internal consistency reliability, the four subscales prove a fairly good consistency with α coefficients above 0.7. Average values of statistical variables show significantly lower age of patients with tinnitus and no HL, which can provide a cue of noise overexposure of this segment of population. These younger patients show also decreased ABQ and similar THI in comparison with patients in the other subgroups. A strong correlation (ρ = 0.63) was found between AAT and Age for the HLNTG subgroup. For the HLTG subgroup, a moderate correlation (ρ = 0.44) was found between ABQ and THI. Conclusion: The utilized questionnaire (ABQ), together with AAT and THI, can help to study comorbid hearing impairments in patients regularly attending an audiological clinic. PMID:28428741

Optimizing Clinical Interpretation of Distortion Product Otoacoustic Emissions in Infants.

PubMed

Blankenship, Chelsea M; Hunter, Lisa L; Keefe, Douglas H; Feeney, M Patrick; Brown, David K; McCune, Annie; Fitzpatrick, Denis F; Lin, Li

2018-03-06

The purpose of this study was to analyze distortion product otoacoustic emission (DPOAE) level and signal to noise ratio in a group of infants from birth to 4 months of age to optimize prediction of hearing status. DPOAEs from infants with normal hearing (NH) and hearing loss (HL) were used to predict the presence of conductive HL (CHL), sensorineural HL (SNHL), and mixed HL (MHL). Wideband ambient absorbance was also measured and compared among the HL types. This is a prospective, longitudinal study of 279 infants with verified NH and HL, including conductive, sensorineural, and mixed types that were enrolled from a well-baby nursery and two neonatal intensive care units in Cincinnati, Ohio. At approximately 1 month of age, DPOAEs (1-8 kHz), wideband absorbance (0.25-8 kHz), and air and bone conduction diagnostic tone burst auditory brainstem response (0.5-4 kHz) thresholds were measured. Hearing status was verified at approximately 9 months of age with visual reinforcement audiometry (0.5-4 kHz). Auditory brainstem response air conduction thresholds were used to assign infants to an NH or HL group, and the efficacy of DPOAE data to classify ears as NH or HL was analyzed using receiver operating characteristic (ROC) curves. Two summary statistics of the ROC curve were calculated: the area under the ROC curve and the point of symmetry on the curve at which the sensitivity and specificity were equal. DPOAE level and signal to noise ratio cutoff values were defined at each frequency as the symmetry point on their respective ROC curve, and DPOAE results were combined across frequency in a multifrequency analysis to predict the presence of HL. Single-frequency test performance of DPOAEs was best at mid to high frequencies (3-8 kHz) with intermediate performance at 1.5 and 2 kHz and chance performance at 1 kHz. Infants with a conductive component to their HL (CHL and MHL combined) displayed significantly lower ambient absorbance values than the NH group. No differences in ambient absorbance were found between the NH and SNHL groups. Multifrequency analysis resulted in the best prediction of HL for the SNHL/MHL group with poorer sensitivity values when infants with CHL were included. Clinical interpretation of DPOAEs in infants can be improved by using age-appropriate normative ranges and optimized cutoff values. DPOAE interpretation is most predictive at higher F2 test frequencies in young infants (2-8 kHz) due to poor test performance at 1 to 1.5 kHz. Multifrequency rules can be used to improve sensitivity while balancing specificity. Last, a sensitive middle ear measure such as wideband absorbance should be included in the test battery to assess possibility of a conductive component to the HL.