Does quantitative ultrasound imaging enhance precision and discrimination?

PubMed

Frost, M L; Blake, G M; Fogelman, I

2000-01-01

The aim of this study was to compare quantitative ultrasound (QUS) measurements obtained using a new calcaneal QUS imaging device with a conventional non-imaging device using fixed transducers. The study group consisted of 340 healthy women with no risk factors associated with osteoporosis (176 premenopausal and 164 postmenopausal) and 83 women with one or more vertebral fractures. All women had QUS measurements performed on the Osteometer DTU-one (imaging) and Walker-Sonix UBA575+ (non-imaging) devices and bone mineral density (BMD) measurements performed at the spine and hip. A subgroup of 81 women had additional dual-energy X-ray absorptiometry (DXA) scans at the calcaneus. Short-term standardized precision (SP = SD/young adult SD) based on duplicate measurements was significantly better on the DTU for broadband ultrasound attenuation (BUA) (SP: DTU 0.15 vs UBA 0.21,p = 0.01) and speed of sound (SOS) (SP: DTU 0.14 vs UBA 0.18, p = 0.01). However, long-term SP of the DTU was comparable to or significantly poorer than the SP of the UBA device. The BUA and SOS measurements obtained on the DTU and UBA were significantly correlated (r = 0.76 and 0.89 for BUA and SOS measurements respectively). The correlations between QUS and BMD measurements were all significant, ranging from 0.53 to 0.72. No significant improvements in the correlation with axial or peripheral BMD were observed using the imaging device. All the QUS measurement parameters showed a significant negative relationship between age and years since menopause in the postmenopausal group. Annual losses were lower for the DTU for BUA (DTU 0.22 dB/MHz per year vs UBA 0.44 dB/MHz per year) but comparable for SOS (DTU 0.29 m/s per-year vs UBA 0.22 m/s per year). However, when these figures were standardized to take into account the clinical range, the annual losses were similar on the DTU and UBA. Age-adjusted odds ratios for each SD decline were similar on the DTU for BUA (DTU 3.2 vs UBA 3.3) and SOS (DTU 3.4 vs UBA 5.1). The corresponding odds ratios for BMD at the lumbar spine, femoral neck and total hip were 2.7, 2.9 and 3.3 respectively. Age-adjusted receiver-operating characteristics analysis yielded values for the area under the curve (AUC) ranging from 0.74 to 0.83. The DTU BUA AUC of 0.83 was significantly greater than the AUC obtained for UBA BUA and BMD measurements at the lumbar spine and femoral neck. Ultrasound imaging at the calcaneus was found to improve the standardized precision of BUA and SOS measurements in the short term but not in the long term. Neither the correlation with BMD nor the discriminatory ability of QUS was improved by utilizing QUS images at the calcaneus. The inconsistencies of the imaging system used for this study demonstrate that further development is required before it will be possible to show improvements in long-term precision.

Impairment of social behavior and communication in mice lacking the Uba6-dependent ubiquitin activation system.

PubMed

Lee, Ji Yeon; Kwak, Minseok; Lee, Peter C W

2015-03-15

The Uba6-Use1 ubiquitin enzyme cascade is a poorly understood arm of the ubiquitin-proteasome system required for mouse development. Recently, we reported that Uba6 brain-specific knockout (termed NKO) mice display abnormal social behavior and neuronal development due to a decreased spine density and accumulation of Ube3a and Shank3. To better characterize a potential role for NKO mice in autism spectrum disorders (ASDs), we performed a comprehensive behavioral characterization of the social behavior and communication of NKO mice. Our behavioral results confirmed that NKO mice display social impairments, as indicated by fewer vocalizations and decreased social interaction. We conclude that UBA6 NKO mice represent a novel ASD mouse model of anti-social and less verbal behavioral symptoms. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel TDP2-ubiquitin interactions and their importance for the repair of topoisomerase II-mediated DNA damage

PubMed Central

Rao, Timsi; Gao, Rui; Takada, Saeko; Al Abo, Muthana; Chen, Xiang; Walters, Kylie J.; Pommier, Yves; Aihara, Hideki

2016-01-01

Tyrosyl DNA phosphodiesterase 2 (TDP2) is a multifunctional protein implicated in DNA repair, signal transduction and transcriptional regulation. In its DNA repair role, TDP2 safeguards genome integrity by hydrolyzing 5′-tyrosyl DNA adducts formed by abortive topoisomerase II (Top2) cleavage complexes to allow error-free repair of DNA double-strand breaks, thereby conferring cellular resistance against Top2 poisons. TDP2 consists of a C-terminal catalytic domain responsible for its phosphodiesterase activity, and a functionally uncharacterized N-terminal region. Here, we demonstrate that this N-terminal region contains a ubiquitin (Ub)-associated (UBA) domain capable of binding multiple forms of Ub with distinct modes of interactions and preference for either K48- or K63-linked polyUbs over monoUb. The structure of TDP2 UBA bound to monoUb shows a canonical mode of UBA-Ub interaction. However, the absence of the highly conserved MGF motif and the presence of a fourth α-helix make TDP2 UBA distinct from other known UBAs. Mutations in the TDP2 UBA-Ub binding interface do not affect nuclear import of TDP2, but severely compromise its ability to repair Top2-mediated DNA damage, thus establishing the importance of the TDP2 UBA–Ub interaction in DNA repair. The differential binding to multiple Ub forms could be important for responding to DNA damage signals under different contexts or to support the multi-functionality of TDP2. PMID:27543075

Hot isostatically pressed manufacture of high strength MERL 76 disk and seal shapes

NASA Technical Reports Server (NTRS)

Evans, D. J.

1982-01-01

The performance of a HIP MERL 76 disk installed in an experimental engine and exposed to realistic operating conditions in a 150 hour, 1500 cycle endurance test is examined. Post test analysis, based on visual, fluorescence penetrant and dimensional inspection, indicates that the disk performs satisfactorily.

Keap1/Cullin3 Modulates p62/SQSTM1 Activity via UBA Domain Ubiquitination.

PubMed

Lee, YouJin; Chou, Tsui-Fen; Pittman, Sara K; Keith, Amy L; Razani, Babak; Weihl, Conrad C

2017-04-04

p62/SQSTM1 (p62) is a scaffolding protein that facilitates the formation and degradation of ubiquitinated aggregates via its self-interaction and ubiquitin binding domains. The regulation of this process is unclear but may relate to the post-translational modification of p62. In the present study, we find that Keap1/Cullin3 ubiquitinates p62 at lysine 420 within its UBA domain. Substitution of lysine 420 with an arginine diminishes p62 sequestration and degradation activity similar what is seen when the UBA domain is deleted. Overexpression of Keap1/Cullin3 in p62-WT-expressing cells increases ubiquitinated inclusion formation and p62's association with LC3 and rescues proteotoxicity. This effect is not seen in cells expressing a mutant p62 that fails to interact with Keap1. Interestingly, p62 disease mutants have diminished or absent UBA domain ubiquitination. These data suggest that the ubiquitination of p62's UBA domain at lysine 420 may regulate p62's function and be disrupted in p62-associated disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Merlin C. Wittrock and the Revision of Bloom's Taxonomy

ERIC Educational Resources Information Center

Krathwohl, David R.; Anderson, Lorin W.

2010-01-01

Merl Wittrock, a cognitive psychologist who had proposed a generative model of learning, was an essential member of the group that over a period of 5 years revised the "Taxonomy of Educational Objectives," originally published in 1956. This article describes the development of that 2001 revision (Anderson and Krathwohl, Editors) and Merl's…

Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function

PubMed Central

Smith, Gina A.; Fearnley, Gareth W.; Abdul-Zani, Izma; Wheatcroft, Stephen B.; Tomlinson, Darren C.; Harrison, Michael A.

2017-01-01

ABSTRACT Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) regulate signal transduction and angiogenesis, but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated endothelial cell response. VEGFR2 undergoes VEGF-A-independent constitutive degradation via a UBA1-dependent ubiquitin-linked pathway. Depletion of UBA1 increased VEGFR2 recycling from endosome-to-plasma membrane and decreased proteolysis. Increased membrane receptor availability after UBA1 depletion elevated VEGF-A-stimulated activation of key signaling enzymes such as PLCγ1 and ERK1/2. Although UBA1 depletion caused an overall decrease in endothelial cell proliferation, surviving cells showed greater VEGF-A-stimulated responses such as cell migration and tubulogenesis. Our study now suggests that a ubiquitin-linked pathway regulates the balance between receptor recycling and degradation which in turn impacts on the intensity and duration of VEGF-A-stimulated signal transduction and the endothelial response. PMID:28798148

Summary Report for the Environmental Protection Agency MERL/FRMAC Mission Alignment Exercise held at the Environmental Protection Agency Facility on June 24-26 2014

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

Allen, Mark B.; Shanks, Sonoya Toyoko; Fournier, Sean Donovan

From June 24th thru June 26th 2014, members of the Federal Radiological Monitoring and Assessment Center (FRMAC), FRMAC Fly Away Laboratory, and the Environmental Protection Agency (EPA) participated in a joint nuclear incident emergency response/round robin exercise at the EPA facility in Las Vegas, Nevada. The purpose of this exercise was to strengthen the interoperability relationship between the FRMAC Fly Away Laboratory (FAL) and the EPA Mobile Environmental Radiation Laboratory (MERL) stationed in Las Vegas, Nevada. The exercise was designed to allow for immediate delivery of pre-staged, spiked samples to the EPA MERL and the FAL for sample preparation andmore » radiological analysis. Upon completion of laboratory analysis, data was reviewed and submitted back to the FRMAC via an electronic data deliverable (EDD). In order to conduct a laboratory inter-comparison study, samples were then traded between the two laboratories and re-counted. As part of the exercise, an evaluation was conducted to identify gaps and potential areas for improvements for FRMAC, FAL and EPA operations. Additionally, noteworthy practices and potential future areas of interoperability opportunities between the FRMAC, FAL and EPA were acknowledged. The exercise also provided a unique opportunity for FRMAC personnel to observe EPA sample receipt and sample preparation processes and to gain familiarity with the MERL laboratory instrumentation and radiation detection capabilities. The areas for potential improvements and interoperability from this exercise will be critical for developing a more efficient, integrated response for future interactions between the FRMAC and EPA MERL assets.« less

Robert Merle d’Aubigné, 1900–1989

PubMed Central

Biau, David J.

2008-01-01

This biographical sketch of R. Merle d’Aubigné corresponds to the historic text, The Classic: Functional Results of Hip Arthroplasty with Acrylic Prosthesis, available at DOI 10.1007/s11999-008-0572-1. Electronic supplementary material The online version of this article (doi:10.1007/s11999-008-0571-2) contains supplementary material, which is available to authorized users. PMID:18941853

Army Business Transformation: The Utility of Using Corporate Business Models within the Institutional Army

DTIC Science & Technology

2007-06-01

Manufacturing by Dr. Robert N. Castellano,3 Essentials of Economics by Damodar Gujarati, New Product Management by Merle Crawford and Anthony Di... Essentials of Economics by Damodar Gujarati, New Product Management by Merle Crawford and Anthony Di Benedetto, Seeing What’s next by Clayton M...attempting to explain how corporations make money. The Essentials of Economics acknowledges that the law of supply and demand is a good model for

Identification of primary and secondary UBA footprints on the surface of ubiquitin in cell-mimicking crowded solution.

PubMed

Munari, Francesca; Bortot, Andrea; Zanzoni, Serena; D'Onofrio, Mariapina; Fushman, David; Assfalg, Michael

2017-04-01

Despite significant advancements in our understanding of ubiquitin-mediated signaling, the influence of the intracellular environment on the formation of transient ubiquitin-partner complexes remains poorly explored. In our work, we introduce macromolecular crowding as a first level of complexity toward the imitation of a cellular environment in the study of such interactions. Using NMR spectroscopy, we find that the stereospecific complex of ubiquitin and the ubiquitin-associated domain (UBA) is minimally perturbed by the crowding agent Ficoll. However, in addition to the primary canonical recognition patch on ubiquitin, secondary patches are identified, indicating that in cell-mimicking crowded solution, UBA contacts ubiquitin at multiple sites. © 2017 Federation of European Biochemical Societies.

[Scientific production from public hospitals of the City of Buenos Aires, 2017].

PubMed

Ibarra, Mariano; Torrents, Milagros; Ossorio, María Fabiana; Ferrero, Fernando

2018-01-01

The number of publications in the scientific literature coming from an institution is an indicator of its scientific production. The scientific production of the hospitals of the Government of the City of Buenos Aires (GCBA) has been evaluated previously, but without discriminating how much of that production corresponded to other academic institutions settled there (University of Buenos Aires, UBA, National Council of Scientific Research and Techniques, CONICET). Our objective was to evaluate the publications included in PubMed that correspond to hospitals of the GCBA, describe their main characteristics, and discriminate the contribution of other academic institutions (UBA and CONICET). It is a cross-sectional study based on a PubMed search, using the name of each of the 34 GCBA hospitals, CONICET and UBA in the "affiliation" field. In total, 2727 publications from GCBA hospitals were identified (4.6% of Argentine publications); 73.9% in English, 78.9% in relation to humans, 37.2% in the last 5 years; 6.4% with high level of evidence (clinical trials and meta-analysis), and 28.4% including children. Compared to the national total, the GCBA publications include fewer works in English, more research in humans, more clinical trials and more research in children. Of the publications corresponding to hospitals of the GCBA, 90.4% did not share the affiliation with CONICET or with UBA. In conclusion, the GCBA hospitals generated 4.6% of the total Argentine publications in PubMed; and 90% of these was not shared with UBA or CONICET. Publications from GCBA institutions include more clinical trials and research in children.

Oxygen monitor for semi-closed rebreathers: design and use for estimating metabolic oxygen consumption

NASA Astrophysics Data System (ADS)

Clarke, John R.; Southerland, David

1999-07-01

Semi-closed circuit underwater breathing apparatus (UBA) provide a constant flow of mixed gas containing oxygen and nitrogen or helium to a diver. However, as a diver's work rate and metabolic oxygen consumption varies, the oxygen percentages within the UBA can change dramatically. Hence, even a resting diver can become hypoxic and become at risk for oxygen induced seizures. Conversely, a hard working diver can become hypoxic and lose consciousness. Unfortunately, current semi-closed UBA do not contain oxygen monitors. We describe a simple oxygen monitoring system designed and prototyped at the Navy Experimental Diving Unit. The main monitor components include a PIC microcontroller, analog-to-digital converter, bicolor LED, and oxygen sensor. The LED, affixed to the diver's mask is steady green if the oxygen partial pressure is within pre- defined acceptable limits. A more advanced monitor with a depth senor and additional computational circuitry could be used to estimate metabolic oxygen consumption. The computational algorithm uses the oxygen partial pressure and the diver's depth to compute O2 using the steady state solution of the differential equation describing oxygen concentrations within the UBA. Consequently, dive transients induce errors in the O2 estimation. To evalute these errors, we used a computer simulation of semi-closed circuit UBA dives to generate transient rich data as input to the estimation algorithm. A step change in simulated O2 elicits a monoexponential change in the estimated O2 with a time constant of 5 to 10 minutes. Methods for predicting error and providing a probable error indication to the diver are presented.

Predictive value of clinical scoring and simplified gait analysis for acetabulum fractures.

PubMed

Braun, Benedikt J; Wrona, Julian; Veith, Nils T; Rollman, Mika; Orth, Marcel; Herath, Steven C; Holstein, Jörg H; Pohlemann, Tim

2016-12-01

Fractures of the acetabulum show a high, long-term complication rate. The aim of the present study was to determine the predictive value of clinical scoring and standardized, simplified gait analysis on the outcome after these fractures. Forty-one patients with acetabular fractures treated between 2008 and 2013 and available, standardized video recorded aftercare were identified from a prospective database. A visual gait score was used to determine the patients walking abilities 6-m postoperatively. Clinical (Merle d'Aubigne and Postel score, visual analogue scale pain, EQ5d) and radiological scoring (Kellgren-Lawrence score, postoperative computed tomography, and Matta classification) were used to perform correlation and multivariate regression analysis. The average patient age was 48 y (range, 15-82 y), six female patients were included in the study. Mean follow-up was 1.6 y (range, 1-2 y). Moderate correlation between the gait score and outcome (versus EQ5d: r s  = 0.477; versus Merle d'Aubigne: r s  = 0.444; versus Kellgren-Lawrence: r s  = -0.533), as well as high correlation between the Merle d'Aubigne score and outcome were seen (versus EQ5d: r s  = 0.575; versus Merle d'Aubigne: r s  = 0.776; versus Kellgren-Lawrence: r s  = -0.419). Using a multivariate regression model, the 6 m gait score (B = -0.299; P < 0.05) and early osteoarthritis development (B = 1.026; P < 0.05) were determined as predictors of final osteoarthritis. A good fit of the regression model was seen (R 2  = 904). Easy and available clinical scoring (gait score/Merle d'Aubigne) can predict short-term radiological and functional outcome after acetabular fractures with sufficient accuracy. Decisions on further treatment and interventions could be based on simplified gait analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

Domain alternation and active site remodeling are conserved structural features of ubiquitin E1.

PubMed

Lv, Zongyang; Yuan, Lingmin; Atkison, James H; Aldana-Masangkay, Grace; Chen, Yuan; Olsen, Shaun K

2017-07-21

E1 enzymes for ubiquitin (Ub) and Ub-like modifiers (Ubls) harbor two catalytic activities that are required for Ub/Ubl activation: adenylation and thioester bond formation. Structural studies of the E1 for the Ubl s mall u biquitin-like mo difier (SUMO) revealed a single active site that is transformed by a conformational switch that toggles its competency for catalysis of these two distinct chemical reactions. Although the mechanisms of adenylation and thioester bond formation revealed by SUMO E1 structures are thought to be conserved in Ub E1, there is currently a lack of structural data supporting this hypothesis. Here, we present a structure of Schizosaccharomyces pombe Uba1 in which the second catalytic cysteine half-domain (SCCH domain) harboring the catalytic cysteine has undergone a 106° rotation that results in a completely different network of intramolecular interactions between the SCCH and adenylation domains and translocation of the catalytic cysteine 12 Å closer to the Ub C terminus compared with previous Uba1 structures. SCCH domain alternation is accompanied by conformational changes within the Uba1 adenylation domains that effectively disassemble the adenylation active site. Importantly, the structural and biochemical data suggest that domain alternation and remodeling of the adenylation active site are interconnected and are intrinsic structural features of Uba1 and that the overall structural basis for adenylation and thioester bond formation exhibited by SUMO E1 is indeed conserved in Ub E1. Finally, the mechanistic insights provided by the novel conformational snapshot of Uba1 presented in this study may guide efforts to develop small molecule inhibitors of this critically important enzyme that is an active target for anticancer therapeutics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Prevalence of unilateral and bilateral deafness in border collies and association with phenotype.

PubMed

Platt, Simon; Freeman, Julia; di Stefani, Alberta; Wieczorek, Lara; Henley, William

2006-01-01

Congenital sensorineural deafness (CSD) occurs in Border Collies, but its prevalence and inheritance are unknown. This study estimated the prevalence of CSD in Border Collies and investigated its association with phenotypic attributes linked to the merle gene, including coat pigmentation and iris color. Deafness in Border Collies is associated with pigmentation patterns linked to the merle gene. A total of 2597 Border Collies from the United Kingdom. A retrospective study of Border Collies tested, during 1994-2002, by using brainstem auditory evoked responses. Associations between deafness and phenotypic attributes were assessed by using generalized logistic regression. The prevalence of CSD in puppies was estimated as 2.8%. The corresponding rates of unilateral and bilateral CSD were 2.3 and 0.5%, respectively. Adjustment for clustering of hearing status by litter reduced the overall prevalence estimate to 1.6%. There was no association between CSD and sex (P = .2). Deaf Border Collies had higher rates of merle coat pigmentation, blue iris pigment, and excess white on the head than normal hearing Border Collies (all P < .001). The odds of deafness were increased by a factor of 14 for Border Collies with deaf dams, relative to the odds for dogs with normal dams (P = .007), after adjustment for phenotypic attributes. Associations between CSD and pigmentation patterns linked to the merle gene were demonstrated for Border Collies. Evidence for an inherited component to CSD in Border Collies supports selective breeding from only tested and normal parents to reduce the prevalence of this disease.

The SUMO Pathway Is Developmentally Regulated and Required for Programmed DNA Elimination in Paramecium tetraurelia† ‡

PubMed Central

Matsuda, Atsushi; Forney, James D.

2006-01-01

Extensive genome-wide remodeling occurs during the formation of the somatic macronuclei from the germ line micronuclei in ciliated protozoa. This process is limited to sexual reproduction and includes DNA amplification, chromosome fragmentation, and the elimination of internal segments of DNA. Our efforts to define the pathways regulating these events revealed a gene encoding a homologue of ubiquitin activating enzyme 2 (UBA2) that is upregulated at the onset of macronuclear development in Paramecium tetraurelia. Uba2 enzymes are known to activate the protein called small ubiquitin-related modifier (SUMO) that is covalently attached to target proteins. Consistent with this relationship, Northern analysis showed increased abundance of SUMO transcripts during sexual reproduction in Paramecium. RNA interference (RNAi) against UBA2 or SUMO during vegetative growth had little effect on cell survival or fission rates. In contrast, RNAi of mating cells resulted in failure to form a functional macronucleus. Despite normal amplification of the genome, excision of internal eliminated sequences was completely blocked. Additional experiments showed that the homologous UBA2 and SUMO genes in Tetrahymena thermophila are also upregulated during conjugation. These results provide evidence for the developmental regulation of the SUMO pathway in ciliates and suggest a key role for the pathway in controlling genome remodeling. PMID:16682458

Structure and inhibition analysis of the mouse SAD-B C-terminal fragment.

PubMed

Ma, Hui; Wu, Jing-Xiang; Wang, Jue; Wang, Zhi-Xin; Wu, Jia-Wei

2016-10-01

The SAD (synapses of amphids defective) kinases, including SAD-A and SAD-B, play important roles in the regulation of neuronal development, cell cycle, and energy metabolism. Our recent study of mouse SAD-A identified a unique autoinhibitory sequence (AIS), which binds at the junction of the kinase domain (KD) and the ubiquitin-associated (UBA) domain and exerts autoregulation in cooperation with UBA. Here, we report the crystal structure of the mouse SAD-B C-terminal fragment including the AIS and the kinase-associated domain 1 (KA1) at 2.8 Å resolution. The KA1 domain is structurally conserved, while the isolated AIS sequence is highly flexible and solvent-accessible. Our biochemical studies indicated that the SAD-B AIS exerts the same autoinhibitory role as that in SAD-A. We believe that the flexible isolated AIS sequence is readily available for interaction with KD-UBA and thus inhibits SAD-B activity.

Summary Report for the Environmental Protection Agency MERL/FRMAC/RAP Mission Alignment Exercise held at the Savannah River Site on June 9-13 2014

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

Allen, Mark B.; Shanks, Sonoya Toyoko; Fournier, Sean Donovan

From June 9th thru June 13th 2014, members of the Federal Radiological Monitoring and Assessment Center (FRMAC), the Environmental Protection Agency (EPA) and the Department of Energy Radiological Assistance Program (DOE RAP) Region-3 participated in a joint nuclear incident emergency response exercise at the Savannah River Site (SRS) near Aiken, South Carolina. The purpose of this exercise was to strengthen the interoperability relationship between the FRMAC, RAP, and the EPA Mobile Environmental Radiation Laboratory (MERL) stationed in Montgomery, Alabama. The exercise was designed to allowed members of the DOE RAP Region-3 team to collect soil, water, vegetation and air samplesmore » from SRS and submit them through an established FRMAC hotline. Once received and processed through the hotline, FRMAC delivered the samples to the EPA MERL for sample preparation and laboratory radiological analysis. Upon completion of laboratory analysis, data was reviewed and submitted back to FRMAC via an electronic data deliverable (EDD). As part of the exercise, an evaluation was conducted to identify gaps and potential improvements in each step of the processes. Additionally, noteworthy practices and potential future areas of interoperability between FRMAC and EPA were acknowledged. The exercise also provided a unique opportunity for FRMAC personnel to observe EPA sample receipt and sample preparation processes and to gain familiarity with the MERL laboratory instrumentation and radiation detection capabilities. The observations and lessons-learned from this exercise will be critical for developing a more efficient, integrated response for future interactions between the FRMAC and EPA assets.« less

Properties and microstructures for dual alloy combinations of three superalloys with alloy 901

NASA Technical Reports Server (NTRS)

Harf, F. H.

1985-01-01

Dual alloy combinations have potential for use in aircraft engine components such as turbine disks where a wide range of stress and temperature regimes exists during operation. Such alloy combinations may directly result in the conservation of elements which are costly or not available domestically. Preferably, a uniform heat treatment yielding good properties for both alloys should be used. Dual alloy combinations of iron rich Alloy 901 with nickel base superalloys Rene 95, Astroloy, or MERL 76 were not isostatically pressed from prealloyed powders. Individual alloys, alloy mixtures, and layered alloy combinations were given the heat treatments specified for their use in turbine disks or appropriate for Alloy 901. Selected specimens were overaged for 1500 hr at 650 C. Metallographic examinations revealed the absence of phases not originally present in either alloy of a combination. Mechanical tests showed adequate properties in combinations of Rene 95 or Astroloy with Alloy 901 when given the Alloy 901 heat treatment. Combinations with MERL 76 had better properties when given the MERL 76 heat treatment. The results indicate that these combinations are promising candidates for use in turbine disks.

Atmospheric CO2 Records from Sites in the Umweltbundesamt (UBA) Air Sampling Network (1972 - 1997)

DOE Data Explorer

Fricke, W. [Umweltbundesamt, Offenbach/Main, Germany; Wallasch, M. [Umweltbundesamt, Offenbach/Main, Germany; Uhse, Karin [Umweltbundesamt, Offenbach/Main, Germany; Schmidt, Martina [University of Heidelberg, Heidelberg, Germany; Levin, Ingeborg [University of Heidelberg, Heidelberg, Germany

1998-01-01

Air samples for the purpose of monitoring atmospheric CO2 were collected from five sites in the UBA air sampling network. Annual atmospheric CO2 concentrations at Brotjacklriegel rose from 331.63 parts per million by volume (ppmv) in 1972 to 353.12 ppmv in 1988. Because of the site's forest location, the monthly atmospheric CO2 record from Brotjacklriegel exhibits very large seasonal amplitude. This amplitude reached almost 40 ppmv in 1985. Minimum mixing ratios are recorded at Brotjacklriegel during July-September; maximum values, during November-March. CO2 concentrations at Deuselbach rose from 340.82 parts per million by volume (ppmv) in 1972 to 363.76 ppmv in 1989. The monthly atmospheric CO2 record from Deuselbach is influenced by local agricultural activities and photosynthetic depletion but does not exhibit the large seasonal amplitude observed at other UBA monitoring sites. Minimum monthly atmospheric CO2 mixing ratios at Deuselbach are typically observed in August but may appear as early as June. Maximum values are seen in the record for November-March. Atmospheric CO2 concentrations at Schauinsland rose from ~328 parts per million by volume (ppmv) in 1972 to ~365 ppmv in 1997. This represents a growth rate of approximately 1.5 ppmv per year. The Schauinsland site is considered the least contaminated of the UBA sites. CO2 concentrations at Waldhof rose from 346.82 parts per million by volume (ppmv) in 1972 to 372.09 ppmv in 1993. The Waldhof site is subject to pollution sources; consequently, the monthly atmospheric CO2 record exhibits a large seasonal amplitude. Atmospheric CO2 concentrations at Westerland rose from ~329 parts per million by volume (ppmv) in 1973 to ~364 ppmv in 1997. The atmospheric CO2 record from Westerland shows a seasonal pattern similar to other UBA sites; minimum values are recorded during July-September; maximum mixing ratios during November-March.

DECOMPRESSION FROM He-N2-O2 (TRIMIX) BOUNCE DIVES IS NOT MORE EFFICIENT THAN FROM He-O2 (HELIOX) BOUNCE DIVES

DTIC Science & Technology

2015-05-28

true, trimix would be an attractive alternative to heliox for U. S. Navy MK 16 MOD 1 underwater breathing apparatus (UBA) diving. However, there is no...for the semi-closed circuit Canadian Underwater Mine-countermeasures Apparatus (CUMA) that are shorter than...diving15-17 and by the U.S. Navy for the MK 6 semi- closed circuit underwater breathing apparatus (UBA);18,19 each of these programs tested trimix schedules

Effects of measurement method and transcript availability on inexperienced raters' stuttering frequency scores.

PubMed

Chakraborty, Nalanda; Logan, Kenneth J

To examine the effects of measurement method and transcript availability on the accuracy, reliability, and efficiency of inexperienced raters' stuttering frequency measurements. 44 adults, all inexperienced at evaluating stuttered speech, underwent 20 min of preliminary training in stuttering measurement and then analyzed a series of sentences, with and without access to transcripts of sentence stimuli, using either a syllable-based analysis (SBA) or an utterance-based analysis (UBA). Participants' analyses were compared between groups and to a composite analysis from two experienced evaluators. Stuttering frequency scores from the SBA and UBA groups differed significantly from the experienced evaluators' scores; however, UBA scores were significantly closer to the experienced evaluators' scores and were completed significantly faster than the SBA scores. Transcript availability facilitated scoring accuracy and efficiency in both groups. The internal reliability of stuttering frequency scores was acceptable for the SBA and UBA groups; however, the SBA group demonstrated only modest point-by-point agreement with ratings from the experienced evaluators. Given its accuracy and efficiency advantages over syllable-based analysis, utterance-based fluency analysis appears to be an appropriate context for introducing stuttering frequency measurement to raters who have limited experience in stuttering measurement. To address accuracy gaps between experienced and inexperienced raters, however, use of either analysis must be supplemented with training activities that expose inexperienced raters to the decision-making processes used by experienced raters when identifying stuttered syllables. Copyright © 2018 Elsevier Inc. All rights reserved.

Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation

PubMed Central

Lau, Alan F.

2009-01-01

The ubiquitin–proteasome pathway of protein degradation is one of the major mechanisms that are involved in the maintenance of the proper levels of cellular proteins. The regulation of proteasomal degradation thus ensures proper cell functions. The family of proteins containing ubiquitin-like (UbL) and ubiquitin-associated (UBA) domains has been implicated in proteasomal degradation. UbL–UBA domain containing proteins associate with substrates destined for degradation as well as with subunits of the proteasome, thus regulating the proper turnover of proteins. PMID:19468686

A new group in the Leptospirillum clade: cultivation-independent community genomics, proteomics and transcriptomics of the new species Leptospirillum group IV UBA BS.

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

Goltsman, Daniela; Dasari, Mauna; Thomas, BC

Leptospirillum spp. are widespread members of acidophilic microbial communities that catalyze ferrous iron oxidation, thereby increasing sulfide mineral dissolution rates. These bacteria play important roles in environmental acidification and are harnessed for bioleaching-based metal recovery. Known members of the Leptospirillum clade of the Nitrospira phylum are Leptospirillum ferrooxidans (group I), Leptospirillum ferriphilum and Leptospirillum rubarum (group II), and Leptospirillum ferrodiazotrophum (group III). In the Richmond Mine acid mine drainage (AMD) system, biofilm formation is initiated by L. rubarum; L. ferrodiazotrophum appears in later developmental stages. Here we used community metagenomic data from unusual, thick floating biofilms to identify distinguishing metabolicmore » traits in a rare and uncultivated community member, the new species Leptospirillum group IV UBA BS. These biofilms typically also contain a variety of Archaea, Actinobacteria, and a few other Leptospirillum spp. The Leptospirillum group IV UBA BS species shares 98% 16S rRNA sequence identity and 70% average amino acid identity between orthologs with its closest relative, L. ferrodiazotrophum. The presence of nitrogen fixation and reverse tricarboxylic acid (TCA) cycle proteins suggest an autotrophic metabolism similar to that of L. ferrodiazotrophum, while hydrogenase proteins suggest anaerobic metabolism. Community transcriptomic and proteomic analyses demonstrate expression of a multicopper oxidase unique to this species, as well as hydrogenases and core metabolic genes. Results suggest that the Leptospirillum group IV UBA BS species might play important roles in carbon fixation, nitrogen fixation, hydrogen metabolism, and iron oxidation in some acidic environments.« less

Labral Reattachment in Femoroacetabular Impingement Surgery Results in Increased 10-year Survivorship Compared With Resection.

PubMed

Anwander, Helen; Siebenrock, Klaus A; Tannast, Moritz; Steppacher, Simon D

2017-04-01

Since the importance of an intact labrum for normal hip function has been shown, labral reattachment has become the standard method for open or arthroscopic treatment of hips with femoroacetabular impingement (FAI). However, no long-term clinical results exist evaluating the effect of labral reattachment. A 2-year followup comparing open surgical treatment of FAI with labral resection versus reattachment was previously performed at our clinic. The goal of this study was to report a concise followup of these patients at a minimum of 10 years. We asked if patients undergoing surgical hip dislocation for the treatment of mixed-type FAI with labral reattachment compared with labral resection had (1) improved hip pain and function based on the Merle d'Aubigné-Postel score; and (2) improved survival at 10-year followup. Between June 1999 and July 2002, we performed surgical hip dislocation with femoral neck osteoplasty and acetabular rim trimming in 52 patients (60 hips) with mixed-type FAI. In the first 20 patients (25 hips) until June 2001, a torn labrum or a detached labrum in the area of acetabular rim resection was resected. In the next 32 patients (35 hips), reattachment of the labrum was performed. The same indications were used to perform both procedures during the periods in question. Of the 20 patients (25 hips) in the first group, 19 patients (95%) (24 hips [96%]) were available for clinical and/or radiographic followup at a minimum of 10 years (mean, 13 years; range, 12-14 years). Of the 32 patients (35 hips) in the second group, 29 patients (91%) (32 hips [91%]) were available for clinical and/or radiographic followup at a minimum of 10 years (mean, 12 years; range, 10-13 years). We used the anterior impingement test to assess pain. Function was assessed using the Merle d'Aubigné- Postel score and ROM. Survivorship calculation was performed using the method of Kaplan-Meier with failure defined as conversion to THA, progression of osteoarthritis (of one grade or more on the Tönnis score), and a Merle d'Aubigné-Postel score < 15. At the 10-year followup, hip pain in hips with labral reattachment was slightly improved for the postoperative Merle d'Aubigné-Postel pain subscore (5.0 ± 1.0 [3-6] versus 3.9 ± 1.7 [0-6]; p = 0.017). No difference existed for the prevalence of hip pain assessed using the anterior impingement test with the numbers available (resection group 52% [11 of 21 hips] versus reattachment group 27% [eight of 30 hips]; odds ratio, 3.03; 95% confidence interval [CI], 0.93-9.83; p = 0.062). Function was slightly better in the reattachment group for the overall Merle d'Aubigné-Postel score (16.7 ± 1.5 [13-18] versus 15.3 ± 2.4 [9-18]; p = 0.028) and hip abduction (45° ± 13° [range, 30°-70°] versus 38° ± 8° [range, 25°-45°]; p = 0.001). Hips with labral reattachment showed a better survival rate at 10 years than did hips that underwent labral resection (78%; 95% CI, 64%-92% versus 46%, 95% CI, 26%-66%; p = 0.009) with the endpoints defined as conversion to THA, progression of osteoarthritis, and a Merle d'Aubigné-Postel score < 15. With isolated endpoints, survival at 10 years was increased for labral reattachment and the endpoint Merle d'Aubigné score < 15 (83%, 95% CI, 70%-97% versus 48%, 95% CI, 28%-69%; p = 0.009) but did not differ for progression of osteoarthritis (83%, 95% CI, 68%-97% versus 81%, 95% CI, 63%-98%; p = 0.957) or conversion to THA (94%, 95% CI, 86%-100% versus 87%, 95% CI, 74%-100%; p = 0.366). The current results suggest the importance of preserving the labrum and show that resection may put the hip at risk for early deterioration. At 10-year followup, hips with labral reattachment less frequently had a decreased Merle d'Aubigné score but no effect on progression of osteoarthritis or conversion to THA could be shown. Level III, therapeutic study.

Impacts of Climate Change on Electricity Consumption in Baden-Wuerttemberg

NASA Astrophysics Data System (ADS)

Mimler, S.

2009-04-01

Changes in electricity consumption due to changes in mean air temperatures were examined for the German federal state Baden-Wuerttemberg. Unlike in most recent studies on future electricity demand variations due to climate change, other load influencing factors like the economic, technological and demographic situation were fixed to the state of 2006. This allows isolating the climate change effect on electricity demand. The analysis was realised in two major steps. Firstly, an electricity forecast model based on multiple regressions was estimated on the region of Baden-Wuerttemberg by using historical load and temperature data. The estimation of the forecast model provides information on the temperature sensitivity of electricity demand in the given region. The overall heating and cooling gradients are estimated with -59 and 84 MW / °C respectively. These results already point out a low temperature sensitivity of demand in the region of Baden-Wuerttemberg mostly due to a low share of households equipped with electric heating and air conditioning systems. Secondly, near surface air temperature data of the regional climate model REMO [1] was used to simulate load curves for the control period 1971 to 2000 and for three future scenarios 2006 to 2035, 2036 to 2065 and 2066 to 2095. The results show that the overall load decreases throughout all future scenario periods in comparison to the control period. This is due to a higher decrease in heating than increase in cooling load. Nevertheless, the weather dependent part in Baden-Wuerttemberg loads only accounts for 0.05 % of the average load level. Within this weather dependent part, the heating load decreases are highest in June to September concentrated on the day times evening and afternoon. The cooling period broadens from May to September in the control period to April to October by 2095. The highest relative increases occur in October. Regarding day times, the increase in cooling load is concentrated on afternoons, evenings and nights. [1] Jacob, D. (2005a), "REMO A1B Scenario run, UBA project, 0.088 degree resolution, run no.006211, 1H data", World Data Center for Climate, CERA-DB "REMO_UBA_A1B_1_R006211_1H", http://cera-www.dkrz.de/WDCC/ui/Compact.jsp? acronym=REMO_UBA_A1B_1_R006211_1H Jacob, D. (2005b), "REMO climate of the 20th century run, UBA project, 0.088 degree resolution, run no. 006210, 1H data", World Data Center for Climate, CERA-DB "REMO_UBA_C20_1_R006210_1H", http://cera-www.dkrz.de/WDCC/ui/Compact. jsp?acronym=REMO_UBA_C20_1_R006210_1H

SUMOylation is developmentally regulated and required for cell pairing during conjugation in Tetrahymena thermophila.

PubMed

Nasir, Amjad M; Yang, Qianyi; Chalker, Douglas L; Forney, James D

2015-02-01

The covalent attachment of small ubiquitin-like modifier (SUMO) to target proteins regulates numerous nuclear events in eukaryotes, including transcription, mitosis and meiosis, and DNA repair. Despite extensive interest in nuclear pathways within the field of ciliate molecular biology, there have been no investigations of the SUMO pathway in Tetrahymena. The developmental program of sexual reproduction of this organism includes cell pairing, micronuclear meiosis, and the formation of a new somatic macronucleus. We identified the Tetrahymena thermophila SMT3 (SUMO) and UBA2 (SUMO-activating enzyme) genes and demonstrated that the corresponding green fluorescent protein (GFP) tagged gene products are found predominantly in the somatic macronucleus during vegetative growth. Use of an anti-Smt3p antibody to perform immunoblot assays with whole-cell lysates during conjugation revealed a large increase in SUMOylation that peaked during formation of the new macronucleus. Immunofluorescence using the same antibody showed that the increase was localized primarily within the new macronucleus. To initiate functional analysis of the SUMO pathway, we created germ line knockout cell lines for both the SMT3 and UBA2 genes and found both are essential for cell viability. Conditional Smt3p and Uba2p cell lines were constructed by incorporation of the cadmium-inducible metallothionein promoter. Withdrawal of cadmium resulted in reduced cell growth and increased sensitivity to DNA-damaging agents. Interestingly, Smt3p and Uba2p conditional cell lines were unable to pair during sexual reproduction in the absence of cadmium, consistent with a function early in conjugation. Our studies are consistent with multiple roles for SUMOylation in Tetrahymena, including a dynamic regulation associated with the sexual life cycle. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The HIP2~Ubiquitin Conjugate Forms a Non-Compact Monomeric Thioester during Di-Ubiquitin Synthesis

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

Cook, Benjamin W.; Barber, Kathryn R.; Shilton, Brian H.

2015-03-23

Polyubiquitination is a post-translational event used to control the degradation of damaged or unwanted proteins by modifying the target protein with a chain of ubiquitin molecules. One potential mechanism for the assembly of polyubiquitin chains involves the dimerization of an E2 conjugating enzyme allowing conjugated ubiquitin molecules to be put into close proximity to assist reactivity. HIP2 (UBE2K) and Ubc1 (yeast homolog of UBE2K) are unique E2 conjugating enzymes that each contain a C-terminal UBA domain attached to their catalytic domains, and they have basal E3-independent polyubiquitination activity. Although the isolated enzymes are monomeric, polyubiquitin formation activity assays show thatmore » both can act as ubiquitin donors or ubiquitin acceptors when in the activated thioester conjugate suggesting dimerization of the E2-ubiquitin conjugates. Stable disulfide complexes, analytical ultracentrifugation and small angle x-ray scattering were used to show that the HIP2-Ub and Ubc1-Ub thioester complexes remain predominantly monomeric in solution. Models of the HIP2-Ub complex derived from SAXS data show the complex is not compact but instead forms an open or backbent conformation similar to UbcH5b~Ub or Ubc13~Ub where the UBA domain and covalently attached ubiquitin reside on opposite ends of the catalytic domain. Activity assays showed that full length HIP2 exhibited a five-fold increase in the formation rate of di-ubiquitin compared to a HIP2 lacking the UBA domain. This difference was not observed for Ubc1 and may be attributed to the closer proximity of the UBA domain in HIP2 to the catalytic core than for Ubc1.« less

DNA-damage-inducible 1 protein (Ddi1) contains an uncharacteristic ubiquitin-like domain that binds ubiquitin

PubMed Central

Nowicka, Urszula; Zhang, Daoning; Walker, Olivier; Krutauz, Daria; Castañeda, Carlos A.; Chaturvedi, Apurva; Chen, Tony Y.; Reis, Noa; Glickman, Michael H.; Fushman, David

2015-01-01

SUMMARY Ddi1 belongs to a family of shuttle proteins targeting polyubiquitinated substrates for proteasomal degradation. Unlike the other proteasomal shuttles, Rad23 and Dsk2, Ddi1 remains an enigma: its function is not fully understood and structural properties are poorly characterized. We determined the structure and binding properties of the ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains of Ddi1 from Saccharomyces cerevisiae. We found that, while Ddi1UBA forms a characteristic UBA:ubiquitin complex, Ddi1UBL has entirely uncharacteristic binding preferences. Despite having a ubiquitin-like fold, Ddi1UBL does not interact with typical UBL-receptors but, unexpectedly, binds ubiquitin, forming a unique interface mediated by hydrophobic contacts and by salt-bridges between oppositely-charged residues of Ddi1UBL and ubiquitin. In stark contrast with ubiquitin and other UBLs, the β-sheet surface of Ddi1UBL is negatively charged and, therefore, is recognized in a completely different way. The dual functionality of Ddi1UBL, capable of binding both ubiquitin and proteasome, suggests a novel mechanism for Ddi1 as a proteasomal shuttle. PMID:25703377

PREFACE: 14th Latin American Workshop on Plasma Physics (LAWPP 2011)

NASA Astrophysics Data System (ADS)

Bilbao, Luis; Minotti, Fernando; Kelly, Hector

2012-06-01

These proceedings present the written contributions from participants of the Latin American Workshop on Plasma Physics (LAWPP), which was held in Mar del Plata, Argentina, on 20-25 November 2011. This was the 14th session of the series of LAWPP biennial meetings, which started in 1982. The five-day scientific program of LAWPP 2011 consisted of 32 talks and various poster sessions, with the participation of 135 researchers from Argentina, Brazil, Canada, Chile, Colombia, Mexico, Puerto Rico, USA, Venezuela, as well as others from Europe and Asia. In addition, a School on Plasma Physics and a Workshop on Industrial Applications of Plasma Technology (AITP) were organized together with the main meeting. The five-day School held in the week previous to the meeting was intended for young scientists starting their research in Plasma Physics. On the other hand, the objective of the AITP Workshop was to enhance regional academic and industrial cooperation in the field of plasma assisted surface technology. Topics addressed at LAWPP 2011 included space plasmas, dusty plasmas, nuclear fusion, non-thermal plasmas, basic plasma processes, plasma simulation and industrial plasma applications. This variety of subjects is reflected in these proceedings, which the editors hope will result in enjoyable and fruitful reading for those interested in Plasma Physics. It is a pleasure to thank the Institutions that sponsored the meeting, as well as all the participants and collaborators for making this meeting possible. The Editors Luis Bilbao, Fernando Minotti and Hector Kelly LAWPP participants Participants of the 14th Latin American Workshop on Plasma Physics, 20-25 November 2011, Mar del Plata, Argentina International Scientific Committee Carlos Alejaldre, Spain María Virginia Alves, Brazil Ibere Caldas, Brazil Luis Felipe Delgado-Aparicio, Peru Mayo Villagrán, Mexico Kohnosuke Sato, Japan Héctor Kelly, Argentina Edberto Leal-Quirós, Puerto Rico George Morales, USA Julio Puerta, Venezuela Leopoldo Soto, Chile Michael Tendler, Sweden Carlos Varandas, Portugal Henry Riascos, Colombia Ivan Vargas-Blanco, Costa Rica Local Organizing Committee Luis Bilbao (Chairman) Fernando Minotti (Vice-Chairman) Luis Bernal, UNMDP Alejandro Clausse, PLADEMA-CNEA Graciela Gnavi, INFIP, CONICET-UBA Fausto Gratton, INFIP, CONICET-UBA Diana Grondona, INFIP, CONICET-UBA Héctor Kelly, INFIP, CONICET-UBA Adriana Márquez, INFIP, CONICET-UBA María Milanese, UNCPBA César Moreno, INFIP, CONICET-UBA Sponsors Instituto de Física del Plasma (INFIP) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) Comisión Nacional de Energía Atómica (CNEA) Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) Centro Latino-Americano de Física (CLAF) Universidad Nacional de Mar del Plata (UNMP) Universidad Nacional del Centro de la Provincia de Buenos Aires (UNICEN) Academia Nacional de Ciencias de Buenos Aires (ANCBA) Conference poster

Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy.

PubMed

Muona, Mikko; Ishimura, Ryosuke; Laari, Anni; Ichimura, Yoshinobu; Linnankivi, Tarja; Keski-Filppula, Riikka; Herva, Riitta; Rantala, Heikki; Paetau, Anders; Pöyhönen, Minna; Obata, Miki; Uemura, Takefumi; Karhu, Thomas; Bizen, Norihisa; Takebayashi, Hirohide; McKee, Shane; Parker, Michael J; Akawi, Nadia; McRae, Jeremy; Hurles, Matthew E; Kuismin, Outi; Kurki, Mitja I; Anttonen, Anna-Kaisa; Tanaka, Keiji; Palotie, Aarno; Waguri, Satoshi; Lehesjoki, Anna-Elina; Komatsu, Masaaki

2016-09-01

The ubiquitin fold modifier 1 (UFM1) cascade is a recently identified evolutionarily conserved ubiquitin-like modification system whose function and link to human disease have remained largely uncharacterized. By using exome sequencing in Finnish individuals with severe epileptic syndromes, we identified pathogenic compound heterozygous variants in UBA5, encoding an activating enzyme for UFM1, in two unrelated families. Two additional individuals with biallelic UBA5 variants were identified from the UK-based Deciphering Developmental Disorders study and one from the Northern Finland Intellectual Disability cohort. The affected individuals (n = 9) presented in early infancy with severe irritability, followed by dystonia and stagnation of development. Furthermore, the majority of individuals display postnatal microcephaly and epilepsy and develop spasticity. The affected individuals were compound heterozygous for a missense substitution, c.1111G>A (p.Ala371Thr; allele frequency of 0.28% in Europeans), and a nonsense variant or c.164G>A that encodes an amino acid substitution p.Arg55His, but also affects splicing by facilitating exon 2 skipping, thus also being in effect a loss-of-function allele. Using an in vitro thioester formation assay and cellular analyses, we show that the p.Ala371Thr variant is hypomorphic with attenuated ability to transfer the activated UFM1 to UFC1. Finally, we show that the CNS-specific knockout of Ufm1 in mice causes neonatal death accompanied by microcephaly and apoptosis in specific neurons, further suggesting that the UFM1 system is essential for CNS development and function. Taken together, our data imply that the combination of a hypomorphic p.Ala371Thr variant in trans with a loss-of-function allele in UBA5 underlies a severe infantile-onset encephalopathy. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Performance characterization of high quantum efficiency metal package photomultiplier tubes for time-of-flight and high-resolution PET applications.

PubMed

Ko, Guen Bae; Lee, Jae Sung

2015-01-01

Metal package photomultiplier tubes (PMTs) with a metal channel dynode structure have several advanced features for devising such time-of-flight (TOF) and high spatial resolution positron emission tomography (PET) detectors, thanks to their high packing density, large effective area ratio, fast time response, and position encoding capability. Here, we report on an investigation of new metal package PMTs with high quantum efficiency (QE) for high-resolution PET and TOF PET detector modules. The latest metal package PMT, the Hamamatsu R11265 series, is served with two kinds of photocathodes that have higher quantum efficiency than normal bialkali (typical QE ≈ 25%), super bialkali (SBA; QE ≈ 35%), and ultra bialkali (UBA; QE ≈ 43%). In this study, the authors evaluated the performance of the new PMTs with SBA and UBA photocathodes as a PET detector by coupling various crystal arrays. They also investigated the performance improvements of high QE, focusing in particular on a block detector coupled with a lutetium-based scintillator. A single 4 × 4 × 10 mm(3) LYSO, a 7 × 7 array of 3 × 3 × 20 mm(3) LGSO, a 9 × 9 array of 1.2 × 1.2 × 10 mm(3) LYSO, and a 6 × 6 array of 1.5 × 1.5 × 7 mm(3) LuYAP were used for evaluation. All coincidence data were acquired with a DRS4 based fast digitizer. This new PMT shows promising crystal positioning accuracy, energy and time discrimination performance for TOF, and high-resolution PET applications. The authors also found that a metal channel PMT with SBA was enough for both TOF and high-resolution application, although UBA gave a minor improvement to time resolution. However, significant performance improvement was observed in relative low light output crystals (LuYAP) coupled with UBA. The results of this study will be of value as a useful reference to select PMTs for high-performance PET detectors.

MERL REPORT OF PROGRESS, 1978

EPA Science Inventory

The Municipal Environmental Research Laboratory is EPA's research component for the development of technology, systems and processes to combat environmental pollutants that trouble our communities and municipalities. The report discusses the development and demonstration of cost-...

Implementing a distributed intranet-based information system.

PubMed

O'Kane, K C; McColligan, E E; Davis, G A

1996-11-01

The article discusses Internet and intranet technologies and describes how to install an intranet-based information system using the Merle language facility and other readily available components. Merle is a script language designed to support decentralized medical record information retrieval applications on the World Wide Web. The goal of this work is to provide a script language tool to facilitate construction of efficient, fully functional, multipoint medical record information systems that can be accessed anywhere by low-cost Web browsers to search, retrieve, and analyze patient information. The language allows legacy MUMPS applications to function in a Web environment and to make use of the Web graphical, sound, and video presentation services. It also permits downloading of script applets for execution on client browsers, and it can be used in standalone mode with the Unix, Windows 95, Windows NT, and OS/2 operating systems.

Evolution of tag-based cooperation with emotion on complex networks

NASA Astrophysics Data System (ADS)

Lima, F. W. S.

2018-04-01

We study the evolution of the four strategies: Ethnocentric, altruistic, egoistic and cosmopolitan in one community of individuals through Monte Carlo simulations. Interactions and reproduction among computational agents are simulated on undirected Barabási-Albert (UBA) networks and Erdös-Rènyi random graphs (ER).We study the Hammond-Axelrod model on both UBA networks and ER random graphs for the asexual reproduction case. We use a modified version of the traditional Hammond-Axelrod model and we also allow the agents’ decisions about one of the strategies to take into account the emotion among their equals. Our simulations showed that egoism and altruism win, differently from other results found in the literature where ethnocentric strategy is common.

Transcriptional profiling of MHC class I genes in rainbow trout infected with infectious hematopoietic necrosis virus

USGS Publications Warehouse

Landis, E.D.; Purcell, M.K.; Thorgaard, G.H.; Wheeler, P.A.; Hansen, J.D.

2008-01-01

Major histocompatibility complex (MHC) molecules are important mediators of cell-mediated immunity in vertebrates. MHC class IA molecules are important for host anti-viral immunity as they present intracellular antigens and regulate natural killer cell (NK) activity. MHC class Ib molecules on the other hand are less understood and have demonstrated diverse immune and non-immune functions in mammals. Rainbow trout possess a single classical MHC IA locus (Onmy-UBA) that is believed to function similar to that of mammalian MHC class Ia. Numerous MHC class Ib genes with undetermined functions have also been described in trout. Here we utilize quantitative reverse transcriptase PCR (qRT-PCR) techniques to survey the levels of basal and inducible transcription for selected trout MHC class Ib genes, sIgM and sentinels of IFN induction in response to viral infection. Basal transcription of all the class Ib genes examined in this study was lower than Onmy-UBA in nai??ve fish. UBA, along with all of the non-classical genes were induced in fish infected with virus but not in control fish. Our results support a non-classical designation for the majority of the class IB genes surveyed in this study based upon expression levels while also indicating that they may play an important role in anti-viral immunity in trout.

Lipidation of BmAtg8 is required for autophagic degradation of p62 bodies containing ubiquitinated proteins in the silkworm, Bombyx mori.

PubMed

Ji, Ming-Ming; Lee, Jae Man; Mon, Hiroaki; Iiyama, Kazuhiro; Tatsuke, Tsuneyuki; Morokuma, Daisuke; Hino, Masato; Yamashita, Mami; Hirata, Kazuma; Kusakabe, Takahiro

2017-10-01

p62/Sequestosome-1 (p62/SQSTM1, hereafter referred to as p62) is a major adaptor that allows ubiquitinated proteins to be degraded by autophagy, and Atg8 homologs are required for p62-mediated autophagic degradation, but their relationship is still not understood in Lepidopteran insects. Here it is clearly demonstrated that the silkworm homolog of mammalian p62, Bombyx mori p62 (Bmp62), forms p62 bodies depending on its Phox and Bem1p (PB1) and ubiquitin-associated (UBA) domains. These two domains are associated with Bmp62 binding to ubiquitinated proteins to form the p62 bodies, and the UBA domain is essential for the binding, but Bmp62 still self-associates without the PB1 or UBA domain. The p62 bodies in Bombyx cells are enclosed by BmAtg9-containing membranes and degraded via autophagy. It is revealed that the interaction between the Bmp62 AIM motif and BmAtg8 is critical for the autophagic degradation of the p62 bodies. Intriguingly, we further demonstrate that lipidation of BmAtg8 is required for the Bmp62-mediated complete degradation of p62 bodies by autophagy. Our results should be useful in future studies of the autophagic mechanism in Lepidopteran insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transcriptional profiling of MHC class I genes in rainbow trout infected with infectious hematopoietic necrosis virus

USGS Publications Warehouse

Landis, Eric D.; Purcell, Maureen K.; Thorgaard, Gary H.; Wheeler , Paul A.; Hansen, John D.

2008-01-01

Major histocompatibility complex (MHC) molecules are important mediators of cell-mediated immunity in vertebrates. MHC class IA molecules are important for host anti-viral immunity as they present intracellular antigens and regulate natural killer cell (NK) activity. MHC class Ib molecules on the other hand are less understood and have demonstrated diverse immune and non-immune functions in mammals. Rainbow trout possess a single classical MHC IA locus (Onmy-UBA) that is believed to function similar to that of mammalian MHC class Ia. Numerous MHC class Ib genes with undetermined functions have also been described in trout. Here we utilize quantitative reverse transcriptase PCR (qRT-PCR) techniques to survey the levels of basal and inducible transcription for selected trout MHC class Ib genes, sIgM and sentinels of IFN induction in response to viral infection. Basal transcription of all the class Ib genes examined in this study was lower than Onmy-UBA in naïve fish. UBA, along with all of the non-classical genes were induced in fish infected with virus but not in control fish. Our results support a non-classical designation for the majority of the class IB genes surveyed in this study based upon expression levels while also indicating that they may play an important role in anti-viral immunity in trout.

The RAD23 Family Provides an Essential Connection between the 26S Proteasome and Ubiquitylated Proteins in Arabidopsis[W

PubMed Central

Farmer, Lisa M.; Book, Adam J.; Lee, Kwang-Hee; Lin, Ya-Ling; Fu, Hongyong; Vierstra, Richard D.

2010-01-01

The ubiquitin (Ub)/26S proteasome system (UPS) directs the turnover of numerous regulatory proteins, thereby exerting control over many aspects of plant growth, development, and survival. The UPS is directed in part by a group of Ub-like/Ub-associated (UBL/UBA) proteins that help shuttle ubiquitylated proteins to the 26S proteasome for breakdown. Here, we describe the collection of UBL/UBA proteins in Arabidopsis thaliana, including four isoforms that comprise the RADIATION SENSITIVE23 (RAD23) family. The nuclear-enriched RAD23 proteins bind Ub conjugates, especially those linked internally through Lys-48, via their UBA domains, and associate with the 26S proteasome Ub receptor RPN10 via their N-terminal UBL domains. Whereas homozygous mutants individually affecting the four RAD23 genes are without phenotypic consequences (rad23a, rad23c, and rad23d) or induce mild phyllotaxy and sterility defects (rad23b), higher-order mutant combinations generate severely dwarfed plants, with the quadruple mutant displaying reproductive lethality. Both the synergistic effects of a rad23b-1 rpn10-1 combination and the response of rad23b plants to mitomycin C suggest that RAD23b regulates cell division. Taken together, RAD23 proteins appear to play an essential role in the cell cycle, morphology, and fertility of plants through their delivery of UPS substrates to the 26S proteasome. PMID:20086187

Clinical and neuropathological features of X-linked spinal muscular atrophy (SMAX2) associated with a novel mutation in the UBA1 gene.

PubMed

Dlamini, Nomazulu; Josifova, Dragana J; Paine, Simon M L; Wraige, Elizabeth; Pitt, Matthew; Murphy, Amanda J; King, Andrew; Buk, Stefan; Smith, Frances; Abbs, Stephen; Sewry, Caroline; Jacques, Thomas S; Jungbluth, Heinz

2013-05-01

Infantile-onset X-linked spinal muscular atrophy (SMAX2) is a rare lethal disorder linked to mutations in the UBA1 (previously UBE1) gene, encoding ubiquitin-activating enzyme 1 that has an important role in the ubiquitin-proteasome pathway. Published pathological reports are scarce. Here we report a male infant who presented from birth with predominantly truncal hypotonia following an antenatal history of reduced fetal movements. He had a myopathic face, profound weakness, multiple contractures and areflexia. Creatine kinase was moderately raised. Brain MRI showed non-specific symmetrical periventricular white matter changes. Neurophysiology revealed evidence of motor and sensory involvement and muscle biopsy showed marked inflammatory changes with subtle features suggestive of acute denervation. UBA1 sequencing revealed a novel hemizygous missense mutation (c.1670A>T; p.Glu557Val). He died from progressive respiratory failure at 4 months. On post mortem assessment, in addition to severe ventral motor neuron pathology, there was widespread involvement of the sensory system, as well as developmental and degenerative cerebellar abnormalities. In contrast to typical SMN1-associated SMA, the thalamus was unaffected. These findings indicate that SMAX2 is more accurately classified as a motor sensory neuronopathy rather than a pure anterior horn cell disorder. Ubiquitin-proteasome pathway defects may not only cause neurodegeneration but also affect normal neuronal development. Copyright © 2013 Elsevier B.V. All rights reserved.

Overview of environmental and hydrogeologic conditions at the Merle K. "Mudhole" Smith Airport near Cordova, Alaska

USGS Publications Warehouse

Dorava, J.M.; Sokup, J.M.

1994-01-01

Air service to Cordova, Alaska and the surrounding region is provided by the Merle K. "Mudhole" Smith Airport, 21 kilometers east of the townsite. The Federal Aviation Administration owns or operates support facilities at the airport and wishes to consider the environmental setting and hydro- geologic conditions when evaluating options for remediation of potential contamination at these facilities. The airport is within the Copper River Delta wetlands area and the Chugach National Forest. Silts, sands, and gravels of fluvial origin underlie the airport. Potential flooding may be caused by outbursts of glacier-dammed lakes, glacier icemelt, snowmelt runoff, or precipitation. Surface spills and disposal of hazardous materials in conjunction with precipitation or flooding may adversely affect the quality of ground water. Drinking water at the airport is currently supplied by wells. Alternative drinking-water sources include local rivers and streams, transporting city water from Cordova, or undiscovered aquifers. Each alternative source, however, would likely cost significantly more to develop than using the existing shallow aquifer supply.

[In Process Citation].

PubMed

Kamanzi, Pierre Canisius; Doray, Pierre

2015-02-01

The increase in available student placements at colleges and universities, the implementation of provincial and federal postsecondary education policies, and the rise of the educational aspirations of families and individuals have all led to the massification of Canadian higher education. Based on Merle's typology of the forms of democratization, this article attempts to revisit the theory of equality of opportunities by critically analyzing the link between massification of higher education and social equity. The results of an analysis of longitudinal data from the (YIT) Youth in Transition Survey show that at the age of 24 in 2008, approximately 77% of young Canadians have pursued studies in a college or university. If access to postsecondary education is now higher, to what extent has it improved social equity? The article shows, in light of the Merle's typology, that mass university education is achieved in part under the seal of a segregative democratization, while college education tends to be egalitarian. © 2015 Canadian Sociological Association/La Société canadienne de sociologie.

Genetics Home Reference: spinal muscular atrophy

MedlinePlus

... atrophy types I, II, III, and IV. SMN1 gene mutations lead to a shortage of the SMN protein. ... to be broken down (degraded) within cells. UBA1 gene mutations lead to reduced or absent levels of functional ...

US/German LIMB technology transfer. Final report, March 1984-June 1986

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

Reese, J.L.; Payne, R.; Chughtai, Y.

1988-04-01

The report gives key findings of a program in which the U.S. EPA participated, sponsored by the Umwelbundesamt (UBA), the German equivalent of the EPA. The UBA program included retrofitting the 700 MWe Weiher III utility boiler of the Saarbergwerke AG with staged-mixing burners for NOx control, and sorbent injection for SOx control. The program was considerably reduced in scope because of restrictions placed on the utility by local environmental officials concerning the classification of the fly ash generated in the process. During the limited testing period, SO/sub 2/ emissions were reduced 8-64% depending on Ca/S molar ratio and othermore » operating conditions. An analysis of the test results suggests that the use of more reactive sorbents could increase SO/sub 2/ removals to 30 and 60% at a Ca/S ratio of 2, for limestone and calcium hydroxide, respectively.« less

CG2AA: backmapping protein coarse-grained structures.

PubMed

Lombardi, Leandro E; Martí, Marcelo A; Capece, Luciana

2016-04-15

Coarse grain (CG) models allow long-scale simulations with a much lower computational cost than that of all-atom simulations. However, the absence of atomistic detail impedes the analysis of specific atomic interactions that are determinant in most interesting biomolecular processes. In order to study these phenomena, it is necessary to reconstruct the atomistic structure from the CG representation. This structure can be analyzed by itself or be used as an onset for atomistic molecular dynamics simulations. In this work, we present a computer program that accurately reconstructs the atomistic structure from a CG model for proteins, using a simple geometrical algorithm. The software is free and available online at http://www.ic.fcen.uba.ar/cg2aa/cg2aa.py Supplementary data are available at Bioinformatics online. lula@qi.fcen.uba.ar. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

High Pressure Gas Permeation and Liquid Diffusion Studies of Coflon and Tefzel Thermoplastics. Revision

NASA Technical Reports Server (NTRS)

Morgan, G. J.; Campion, R. P.

1997-01-01

The life of fluid-carrying flexible or umbilical pipes during service at elevated temperatures and pressures depends inter alia on their resistance to attack by the fluids present and the rate at which these fluids are absorbed by the pipe lining materials. The consequences of fluid ingress into the thermoplastic lining could mean a) a reduction in its mechanical strength, to increase chances of crack formation and growth and thus a loss of integrity, b) the occurrence of permeation right through the lining material, with pressure build- up in the outer pipe wall construction (of flexible pipes) or chemical attack (from a hostile permeant) on outer layers of reinforcements. Therefore it is important within this project to have relevant permeation data for Coflon and Tefzel thermoplastics: the former is plasticised, the latter is not. A previous report (CAPP/M.2) described experimental equipment and techniques used by MERL when measuring high pressure (up to 5000 psi) gas permeation and liquid diffusion through thermoplastic samples cut from extruded bar or pipe, and provided the basic theory involved. Norsk Hydro are also performing gas permeation tests on pipe sections, at up to 100 bars (1450 psi) pressure or so, and reporting separately. Some comparisons between data from Norsk Hydro and MERL have been made herein. The tests should be considered as complementary, as the Norsk Hydro test has the obvious benefit of using complete pipe sections, whilst MERL can test at much higher pressures, up to 1000 bar if necessary. The sophisticated analytical measuring equipment of Norsk Hydro can distinguish the individual components of mixed gases and hence the various permeation-linked coefficients whereas MERL, in using pressure increase at constant volume to determine permeation rate, is limited to obtaining single gas data, or apparent (or representative) coefficients for a mixed gas as a whole. Except for the initial fluid diffusion data for Tefzel described in CAPP/M.2, the present report covers all aspects of fluid permeation and diffusion for Coflon and Tefzel, including all the pen-neation data accumulated in the project to date. Test gases have mainly been methane (CH4) and carbon dioxide (CO2). More high pressure (HP) gas permeation tests have been performed since the last issue of this report, most being concerned with changes in permeation characteristics brought about by ageing in various relevant fluids. This revision supersedes previous issues.

Ultrasonography in determining pubertal growth and bone age.

PubMed

Torenek Ağırman, Kubra; Bilge, Osman Murat; Miloğlu, Özkan

2018-05-02

The purpose of this study is to evaluate the compatibility of ultrasonographic data with hand-wrist radiographs taken to determine the extent of pubertal growth and bone age in patients and investigate the usability of ionizing radiation-free ultrasonography instead of conventional radiography. In this study, a total of 120 children from 10 to 17 years old (mean age was 168 months ± 27.5 months) were treated with routine radiographs before orthodontic treatment, and ultrasonographic imaging was performed on the wrists the same day. Researchers examined the phalanges, sesamoid bone, and radial bone distal epiphysis-diaphysis comparatively in each patient by both imaging methods and statistical evaluation. There was no statistically significant difference between conventional radiography and ultrasonography values at 13 points except for PP1 (proximal phalanges of the first finger), PP2 (proximal phalanges of the second finger), and radial epiphysis (p > 0.05). PP1, PP2, and radial epiphysis showed a statistically significant difference (p < 0.05). The CBA (bone age obtained from conventional radiographs) of the females was found to be larger than their CA (chronological age) and their UBA (ultrasonographic bone age). For males; the means of the CBA, UBA and CA values close to each other. In females and males; there was a strong correlation between the CA, the UBA and the CBA (p < 0.01). Ultrasonography gives detailed information about epiphyseal diaphysis relations. It can be used as an alternative to conventional radiography in the detection of bone age and pubertal growth, owing to the absence of ionizing radiation.

Loss of Anticodon Wobble Uridine Modifications Affects tRNALys Function and Protein Levels in Saccharomyces cerevisiae

PubMed Central

Klassen, Roland; Grunewald, Pia; Thüring, Kathrin L.; Eichler, Christian; Helm, Mark; Schaffrath, Raffael

2015-01-01

In eukaryotes, wobble uridines in the anticodons of tRNALys UUU, tRNAGlu UUC and tRNAGln UUG are modified to 5-methoxy-carbonyl-methyl-2-thio-uridine (mcm5s2U). While mutations in subunits of the Elongator complex (Elp1-Elp6), which disable mcm5 side chain formation, or removal of components of the thiolation pathway (Ncs2/Ncs6, Urm1, Uba4) are individually tolerated, the combination of both modification defects has been reported to have lethal effects on Saccharomyces cerevisiae. Contrary to such absolute requirement of mcm5s2U for viability, we demonstrate here that in the S. cerevisiae S288C-derived background, both pathways can be simultaneously inactivated, resulting in combined loss of tRNA anticodon modifications (mcm5U and s2U) without a lethal effect. However, an elp3 disruption strain displays synthetic sick interaction and synergistic temperature sensitivity when combined with either uba4 or urm1 mutations, suggesting major translational defects in the absence of mcm5s2U modifications. Consistent with this notion, we find cellular protein levels drastically decreased in an elp3uba4 double mutant and show that this effect as well as growth phenotypes can be partially rescued by excess of tRNALys UUU. These results may indicate a global translational or protein homeostasis defect in cells simultaneously lacking mcm5 and s2 wobble uridine modification that could account for growth impairment and mainly originates from tRNALys UUU hypomodification and malfunction. PMID:25747122

Loss of anticodon wobble uridine modifications affects tRNA(Lys) function and protein levels in Saccharomyces cerevisiae.

PubMed

Klassen, Roland; Grunewald, Pia; Thüring, Kathrin L; Eichler, Christian; Helm, Mark; Schaffrath, Raffael

2015-01-01

In eukaryotes, wobble uridines in the anticodons of tRNA(Lys)UUU, tRNA(Glu)UUC and tRNA(Gln)UUG are modified to 5-methoxy-carbonyl-methyl-2-thio-uridine (mcm5s2U). While mutations in subunits of the Elongator complex (Elp1-Elp6), which disable mcm5 side chain formation, or removal of components of the thiolation pathway (Ncs2/Ncs6, Urm1, Uba4) are individually tolerated, the combination of both modification defects has been reported to have lethal effects on Saccharomyces cerevisiae. Contrary to such absolute requirement of mcm5s2U for viability, we demonstrate here that in the S. cerevisiae S288C-derived background, both pathways can be simultaneously inactivated, resulting in combined loss of tRNA anticodon modifications (mcm5U and s2U) without a lethal effect. However, an elp3 disruption strain displays synthetic sick interaction and synergistic temperature sensitivity when combined with either uba4 or urm1 mutations, suggesting major translational defects in the absence of mcm5s2U modifications. Consistent with this notion, we find cellular protein levels drastically decreased in an elp3uba4 double mutant and show that this effect as well as growth phenotypes can be partially rescued by excess of tRNA(Lys)UUU. These results may indicate a global translational or protein homeostasis defect in cells simultaneously lacking mcm5 and s2 wobble uridine modification that could account for growth impairment and mainly originates from tRNA(Lys)UUU hypomodification and malfunction.

Defining Weapons of Mass Destruction

DTIC Science & Technology

2012-01-01

physicist Merle Tuve. “Even the atomic bomb didn’t bother him as much as jellied gasoline [napalm].”155 Indeed, it is clear that weapons generally...The official toll was 42,600 dead, not including 2,000 missing. However, the official Royal Air Force history of the bombing campaign suggests that the

78 FR 70027 - Senior Executive Service; Performance Review Board

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-22

.... SYKES, MERLE L. SYNAKOWSKI, EDMUND J. TALBOT JR, GERALD L. TAYLOR, CHARLES W. THOMPSON, MICHAEL A..., WILLIAM N. BURROWS, CHARLES W. BUTTRESS, LARRY D. CADIEUX, GENA E. CALBOS, PHILIP T. CALLAHAN, SAMUEL N..., JAMES MELBOURN DURANT, CHARLES K. ECKROADE, WILLIAM A. EDWARDS III, ROBERT E. EHLI, CATHY L. ELKIND...

Overseas Varietal Analysis 2010 Crop Soft Red Winter Wheat

USDA-ARS?s Scientific Manuscript database

The 2010 U.S. Wheat Associates Overseas Varietal Analysis project evaluated ten soft red winter wheat varieties: Jamestown, Merl and Shirley from Virginia; Coker 9553 and Oakes from North Carolina; Baldwin from Georgia; Renegade and DK 9577 from Arkansas; USG 3555 from Tennessee; and, Malabar from O...

Overseas Varietal Analysis 2011 Crop Soft Red Winter Wheat

USDA-ARS?s Scientific Manuscript database

The 2011 U.S. Wheat Associates Overseas Varietal Analysis project evaluated ten soft red winter wheat varieties: Malabar and AGI 303 from Ohio, Terral TV 8861 from Louisiana, SY 9978 and Coker 9804 from North Carolina, Merl and Shirley from Virginia, AGS 2060 from Arkansas, and USG 3201 and USG 3251...

Exceptional Children Conference Papers: Environmental Influences in the Early Education of Migrant and Disadvantaged Students.

ERIC Educational Resources Information Center

Council for Exceptional Children, Arlington, VA.

Conference papers on early childhood education cover the following topics: individual variation among preschoolers in a cognitive intervention program in low income families presented by Phyllis Levenstein, programmatic research on disadvantaged youth and an ameliorative intervention program by Merle B. Karnes and others, special education and…

Unsupervised Medical Entity Recognition and Linking in Chinese Online Medical Text

PubMed Central

Gan, Liang; Cheng, Mian; Wu, Quanyuan

2018-01-01

Online medical text is full of references to medical entities (MEs), which are valuable in many applications, including medical knowledge-based (KB) construction, decision support systems, and the treatment of diseases. However, the diverse and ambiguous nature of the surface forms gives rise to a great difficulty for ME identification. Many existing solutions have focused on supervised approaches, which are often task-dependent. In other words, applying them to different kinds of corpora or identifying new entity categories requires major effort in data annotation and feature definition. In this paper, we propose unMERL, an unsupervised framework for recognizing and linking medical entities mentioned in Chinese online medical text. For ME recognition, unMERL first exploits a knowledge-driven approach to extract candidate entities from free text. Then, the categories of the candidate entities are determined using a distributed semantic-based approach. For ME linking, we propose a collaborative inference approach which takes full advantage of heterogenous entity knowledge and unstructured information in KB. Experimental results on real corpora demonstrate significant benefits compared to recent approaches with respect to both ME recognition and linking. PMID:29849994

Proteotoxic Stress Induces Phosphorylation of p62/SQSTM1 by ULK1 to Regulate Selective Autophagic Clearance of Protein Aggregates

PubMed Central

Lim, Junghyun; Lachenmayer, M. Lenard; Wu, Shuai; Liu, Wenchao; Kundu, Mondira; Wang, Rong; Komatsu, Masaaki; Oh, Young J.; Zhao, Yanxiang; Yue, Zhenyu

2015-01-01

Disruption of proteostasis, or protein homeostasis, is often associated with aberrant accumulation of misfolded proteins or protein aggregates. Autophagy offers protection to cells by removing toxic protein aggregates and injured organelles in response to proteotoxic stress. However, the exact mechanism whereby autophagy recognizes and degrades misfolded or aggregated proteins has yet to be elucidated. Mounting evidence demonstrates the selectivity of autophagy, which is mediated through autophagy receptor proteins (e.g. p62/SQSTM1) linking autophagy cargos and autophagosomes. Here we report that proteotoxic stress imposed by the proteasome inhibition or expression of polyglutamine expanded huntingtin (polyQ-Htt) induces p62 phosphorylation at its ubiquitin-association (UBA) domain that regulates its binding to ubiquitinated proteins. We find that autophagy-related kinase ULK1 phosphorylates p62 at a novel phosphorylation site S409 in UBA domain. Interestingly, phosphorylation of p62 by ULK1 does not occur upon nutrient starvation, in spite of its role in canonical autophagy signaling. ULK1 also phosphorylates S405, while S409 phosphorylation critically regulates S405 phosphorylation. We find that S409 phosphorylation destabilizes the UBA dimer interface, and increases binding affinity of p62 to ubiquitin. Furthermore, lack of S409 phosphorylation causes accumulation of p62, aberrant localization of autophagy proteins and inhibition of the clearance of ubiquitinated proteins or polyQ-Htt. Therefore, our data provide mechanistic insights into the regulation of selective autophagy by ULK1 and p62 upon proteotoxic stress. Our study suggests a potential novel drug target in developing autophagy-based therapeutics for the treatment of proteinopathies including Huntington’s disease. PMID:25723488

Environmental aspects of hydraulic fracturing - Main results and recommendations from two studies on behalf of the German Environment Agency

NASA Astrophysics Data System (ADS)

Krischbaum, Bernd; Bertram, Andreas; Böttcher, Christian; Iyimen-Schwarz, Züleyha; Rechenberg, Jörg; Dannwolf, Uwe; Meiners, Georg

2016-04-01

The German Environment Agency (UBA) accompanies the debate on fracking for years. Two major reports on risks and environmental impacts regarding the exploration and exploitation of unconventional natural gas, in particular shale gas have been published. On the basis of these studies as well as on scientific evidence UBA considers ecological barriers as a sustainable means to minimize the risks to environment and human health. 1) Recent studies show that the contamination of shallow aquifers by rise of fluids through natural faults or artificially created fractures is extremely unlikely. However, activities on the surface and lack of wellbore integrity pose threats and substantial risks for the quality of shallow aquifers. 2) The need for thorough groundwater monitoring is fully accepted, yet its range and design is subject to discussion. 3) Formerly, analysis and mass balances of flowback and produced water have been insufficient, thus there is a lack of exact information on proportions of frac-fluids, flowback and formation water respectively, as well as data on possible reaction products. 4) Currently, neither on national nor on European level best reference techniques (BREF) for the treatment and disposal of flowback and produced water are available. 5) In addition, land consumption, emission of greenhouse gases, and induced seismicity are major issues. UBA recommends amongst others the implementation of an environmental impact assessment (EIA) for fracking activities, the prohibition of fracking in water protection areas as well as their catchments, and the disclosure of all frac-fluid chemicals within a national chemical registry. To achieve these objectives the German Environment Agency suggests a step-by-step approach. The paper will present the main results from the studies and the recommendations of the German Environment Agency regarding hydraulic fracturing for unconventional gas exploitation.

Structural changes induced by L50P and I61T single mutations of ubiquitin affect cell cycle progression while impairing its regulatory and degradative functions in Saccharomyces cerevisiae.

PubMed

Doshi, Ankita; Sharma, Mrinal; Prabha, C Ratna

2017-06-01

Posttranslational conjugation of ubiquitin to proteins either regulates their function directly or concentration through ubiquitination dependent degradation. High degree of conservation of ubiquitin's sequence implies structural and functional importance of the conserved residues. Ubiquitin gene of Saccharomyces cerevisiae was evolved in vitro by us to study the significance of conserved residues. Present study investigates the structural changes in the protein resulting from the single mutations UbS20F, UbA46S, UbL50P, UbI61T and their functional consequences in the SUB60 strain of S. cerevisiae. Expression of UbL50P and UbI61T decreased Cdc28 protein kinase, enhanced Fus3 levels, caused dosage dependent lethality and at sublethal level produced drastic effects on stress tolerance, protein sorting, protein degradation by ubiquitin fusion degradation pathway and by lysosomes. UbS20F and UbA46S produced insignificant effects over the cells. All four mutations of ubiquitin were incorporated into polyubiquitin. However, polyubiquitination with K63 linkage decreased significantly in cells expressing UbL50P and UbI61T. Structural studies on UbL50P and UbI61T revealed distorted structure with greatly reduced α-helical and elevated β-sheet contents, while UbS20F and UbA46S show mild structural alterations. Our results on functional efficacy of ubiquitin in relation to structural integrity may be useful for designing inhibitors to investigate and modulate eukaryotic cellular dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

Nuclear export of ubiquitinated proteins via the UBIN-POST system

PubMed Central

Sugihara, Munechika; Morito, Daisuke; Iemura, Shun-ichiro; Natsume, Tohru; Nagata, Kazuhiro

2018-01-01

Although mechanisms for protein homeostasis in the cytosol have been studied extensively, those in the nucleus remain largely unknown. Here, we identified that a protein complex mediates export of polyubiquitinated proteins from the nucleus to the cytosol. UBIN, a ubiquitin-associated (UBA) domain-containing protein, shuttled between the nucleus and the cytosol in a CRM1-dependent manner, despite the lack of intrinsic nuclear export signal (NES). Instead, the UBIN binding protein polyubiquitinated substrate transporter (POST) harboring an NES shuttled UBIN through nuclear pores. UBIN bound to polyubiquitin chain through its UBA domain, and the UBIN-POST complex exported them from the nucleus to the cytosol. Ubiquitinated proteins accumulated in the cytosol in response to proteasome inhibition, whereas cotreatment with CRM1 inhibitor led to their accumulation in the nucleus. Our results suggest that ubiquitinated proteins are exported from the nucleus to the cytosol in the UBIN-POST complex-dependent manner for the maintenance of nuclear protein homeostasis. PMID:29666234

New Crop Selection

NASA Technical Reports Server (NTRS)

Bhuiyan, Ruqayah H.; Spencer, Lashelle; Wheeler, Ray; Romeyn, Matthew

2018-01-01

For extended space flight, reliable food supplies are a necessity. Most of the food products consumed by astronauts today are stored for flight via freeze drying. Fresh food is needed to supplement known national deficiencies in the stored food diet (Cooper et al.). This is so because stored foods can lose nutritional value. Fresh food is the answer to the nutritional demands of space flight. Kennedy Space Center's Utilization and Life Sciences Office (UB-A), under the Exploration Research and Technology Program (UB), conducts research on plant growth and development under International Space Station (ISS) conditions. UB-A analyzes the growth responses of leafy greens in microgravity and through the manipulation of environmental conditions (CO2 levels, light intensity, relative humidity, and water delivery). By manipulating growing conditions researchers can optimize food production using minimal/restricted resources. The New Crop Selection experiments are testing the suitability of leafy crops to ISS conditions. Results from this study showed that 'Dragoon' Lettuce and 'Red Russian' Kale have the largest fresh mass.

Sequence analysis of MHC class I α2 from sockeye salmon (Oncorhynchus nerka).

PubMed

McClelland, Erin K; Ming, Tobi J; Tabata, Amy; Miller, Kristina M

2011-09-01

Most studies assessing adaptive MHC diversity in salmon populations have focused on the classical class II DAB or DAA loci, as these have been most amenable to single PCR amplifications due to their relatively low level of sequence divergence. Herein, we report the characterization of the classical class I UBA α2 locus based on collections taken throughout the species range of sockeye salmon (Oncorhynchus nerka). Through use of multiple lineage-specific primer sets, denaturing gradient gel electrophoresis and sequencing, we identified thirty-four alleles from three highly divergent lineages. Sequence identity between lineages ranged from 30.0% to 56.8% but was relatively high within lineages. Allelic identity within the antigen recognition site (ARS) was greater than for the longer sequence. Global positive selection on UBA was seen at the sequence level (dN:dS = 1.012) with four codons under positive selection and 12 codons under negative selection. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Nuclear export of ubiquitinated proteins via the UBIN-POST system.

PubMed

Hirayama, Shoshiro; Sugihara, Munechika; Morito, Daisuke; Iemura, Shun-Ichiro; Natsume, Tohru; Murata, Shigeo; Nagata, Kazuhiro

2018-05-01

Although mechanisms for protein homeostasis in the cytosol have been studied extensively, those in the nucleus remain largely unknown. Here, we identified that a protein complex mediates export of polyubiquitinated proteins from the nucleus to the cytosol. UBIN, a ubiquitin-associated (UBA) domain-containing protein, shuttled between the nucleus and the cytosol in a CRM1-dependent manner, despite the lack of intrinsic nuclear export signal (NES). Instead, the UBIN binding protein polyubiquitinated substrate transporter (POST) harboring an NES shuttled UBIN through nuclear pores. UBIN bound to polyubiquitin chain through its UBA domain, and the UBIN-POST complex exported them from the nucleus to the cytosol. Ubiquitinated proteins accumulated in the cytosol in response to proteasome inhibition, whereas cotreatment with CRM1 inhibitor led to their accumulation in the nucleus. Our results suggest that ubiquitinated proteins are exported from the nucleus to the cytosol in the UBIN-POST complex-dependent manner for the maintenance of nuclear protein homeostasis. Copyright © 2018 the Author(s). Published by PNAS.

Wittrock's Influence on Mathematics Education: Some Personal Comments

ERIC Educational Resources Information Center

Romberg, Thomas A.

2010-01-01

Merlin C. Wittrock was a friend and colleague who influenced me and many other contemporary mathematics educators on how students learn. In this article I summarize my interactions with Merl beginning in 1965, and how over the following half-century he influenced my thinking on student learning for understanding and, in turn, on how to design…

Studies of Gas Turbine Heat Transfer Airfoil Surface and End-Wall.

DTIC Science & Technology

1987-04-01

The nonuniformity 8 of the convex side mainly results from the higher pressure at X/S - 0.43 which might cause the suction side horseshoe vortex to...the toots are available model was chosen. to the authors. Six eses otf lair wed Merle (1961,1962) we also eseeon to Investigate the effects of free

A Vote for Election Science as an Academic Discipline

ERIC Educational Resources Information Center

Foster, Andrea L.

2006-01-01

This article presents the suggestion of Merle S. King, chairman of the department of computer science and information systems at Kennesaw State University and also a director of Kennesaw State's Center for Elections Systems, which has helped establish a uniform statewide voting system in Georgia. On the last day of the conference sponsored by the…

An Alternative Image of "School and Society" and the Dewey Tradition (1950-1980): A Reply to Merle Borrowman.

ERIC Educational Resources Information Center

Wirth, Arthur G.

1981-01-01

Discusses the educational theories of John Dewey in the context of contemporary society. Suggests that although Dewey's approach has merit for an age of turbulent change, it is unlikely that it will receive support. One reason is that society is presently dominated by the values and techniques of Frederick Taylor's scientific efficiency.…

Identification, assessment and management of "endocrine disruptors" in wildlife in the EU substance legislation--discussion paper from the German Federal Environment Agency (UBA).

PubMed

Frische, Tobias; Bachmann, Jean; Frein, Daniel; Juffernholz, Tanja; Kehrer, Anja; Klein, Anita; Maack, Gerd; Stock, Frauke; Stolzenberg, Hans-Christian; Thierbach, Claudia; Walter-Rohde, Susanne

2013-12-16

A discussion paper was developed by a panel of experts of the German Federal Environment Agency (UBA) contributing to the on-going debate on the identification, assessment and management of endocrine disruptors with a view to protect wildlife according to the EU substance legislation (plant protection products, biocides, industrial chemicals). Based on a critical synthesis of the state-of-the-art regarding regulatory requirements, testing methods, assessment schemes, decision-making criteria and risk management options, we advise an appropriate and consistent implementation of this important subject into existing chemicals legislation in Europe. Our proposal for a balanced risk management of endocrine disruptors essentially advocates transparent regulatory decision making based on a scientifically robust weight of evidence approach and an adequate risk management consistent across different legislations. With respect to the latter, a more explicit consideration of the principle of proportionality of regulatory decision making and socio-economic benefits in the on-going debate is further encouraged. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Patterns of selection and allele diversity of class I and class II major histocompatibility loci across the species range of sockeye salmon (Oncorhynchus nerka).

PubMed

McClelland, Erin K; Ming, Tobi J; Tabata, Amy; Kaukinen, Karia H; Beacham, Terry D; Withler, Ruth E; Miller, Kristina M

2013-09-01

The major histocompatibility complex (MHC), an important component of the vertebrate immune system, provides an important suite of genes to examine the role of genetic diversity at non-neutral loci for population persistence. We contrasted patterns of diversity at the two classical MHC loci in sockeye salmon (Oncorhynchus nerka), MHC class I (UBA) and MHC class II (DAB), and neutral microsatellite loci across 70 populations spanning the species range from Washington State to Japan. There was no correlation in allelic richness or heterozygosity between MHC loci or between MHC loci and microsatellites. The two unlinked MHC loci may be responding to different selective pressures; the distribution of FST values for the two loci was uncorrelated, and evidence for both balancing and directional selection on alleles and lineages of DAB and UBA was observed in populations throughout the species range but rarely on both loci within a population. These results suggest that fluctuating selection has resulted in the divergence of MHC loci in contemporary populations. © 2013 John Wiley & Sons Ltd.

Comparison of an imaging heel quantitative ultrasound device (DTU-one) with densitometric and ultrasonic measurements.

PubMed

Diessel, E; Fuerst, T; Njeh, C F; Hans, D; Cheng, S; Genant, H K

2000-01-01

The purpose of this study was to evaluate a new imaging ultrasound scanner for the heel, the DTU-one (Osteometer MediTech, Denmark), by comparing quantitative ultrasound (QUS) results with bone mineral density (BMD) of the heel and femur from dual X-ray absorptiometry (DXA), and by comparing the DTU-one with another QUS device, the UBA 575+. The regions of interest in the DXA heel scan were matched with the regions evaluated by the two QUS devices. 134 healthy and 16 osteoporotic women aged 30-84 years old were enrolled in the study. In vivo short-term precision of the DTU-one for broadband ultrasound attenuation (BUA) and speed of sound (SOS) was 2.9% and 0.1%, respectively, and long-term precision was 3.8% and 0.2%, respectively. Highest correlations (r) between QUS and BMD measurements were achieved when comparing DTU-one results with BMD in matched regions of the DXA heel scan. Correlation coefficients (r) were 0.81 for BUA and SOS. Highest correlations with the UBA 575+ were 0.68 and 0.72, respectively. The comparison of BMD in different femoral sites with BUA and SOS (DTU-one) varied from 0.62 to 0.69 when including the entire study population. The correlation between BMD values within different sites of the femur tended to be higher (from r = 0.81 to 0.93). When comparing BUA with BUA and SOS with SOS on the two QUS devices, the absolute QUS values differed significantly. However, correlations were relatively high, with 0.76 for BUA and 0.82 for SOS. In conclusion, the results of the new quantitative ultrasound device, the DTU-one, are highly correlated (r = 0.8) with results obtained using the UBA 575+ and with BMD in the heel. The precision of the DTU-one is comparable to other QUS devices for BUA and is high for SOS.

Transfer of Ho Endonuclease and Ufo1 to the Proteasome by the UbL-UbA Shuttle Protein, Ddi1, Analysed by Complex Formation In Vitro

PubMed Central

Voloshin, Olga; Bakhrat, Anya; Herrmann, Sharon; Raveh, Dina

2012-01-01

The F-box protein, Ufo1, recruits Ho endonuclease to the SCFUfo1 complex for ubiquitylation. Both ubiquitylated Ho and Ufo1 are transferred by the UbL-UbA protein, Ddi1, to the 19S Regulatory Particle (RP) of the proteasome for degradation. The Ddi1-UbL domain binds Rpn1 of the 19S RP, the Ddi1-UbA domain binds ubiquitin chains on the degradation substrate. Here we used complex reconstitution in vitro to identify stages in the transfer of Ho and Ufo1 from the SCFUfo1 complex to the proteasome. We report SCFUfo1 complex at the proteasome formed in the presence of Ho. Subsequently Ddi1 is recruited to this complex by interaction between the Ddi1-UbL domain and Ufo1. The core of Ddi1 binds both Ufo1 and Rpn1; this interaction confers specificity of SCFUfo1 for Ddi1. The substrate-shield model predicts that Ho would protect Ufo1 from degradation and we find that Ddi1 binds Ho, Ufo1, and Rpn1 simultaneously forming a complex for transfer of Ho to the 19S RP. In contrast, in the absence of Ho, Rpn1 displaces Ufo1 from Ddi1 indicating a higher affinity of the Ddi1-UbL for the 19S RP. However, at high Rpn1 levels there is synergistic binding of Ufo1 to Ddi1 that is dependent on the Ddi1-UbA domain. Our interpretation is that in the absence of substrate, the Ddi1-UbL binds Rpn1 while the Ddi1-UbA binds ubiquitin chains on Ufo1. This would promote degradation of Ufo1 and disassembly of SCFUfo1 complexes. PMID:22815701

Development of a high strength hot isostatically pressed /HIP/ disk alloy, MERL 76

NASA Technical Reports Server (NTRS)

Evans, D. J.; Eng, R. D.

1980-01-01

A nickel-based powder metal disk alloy developed for use in advanced commercial gas turbines is described. Consideration is given to final alloy chemistry modifications made to achieve a desirable balance between tensile strength and stress rupture life and ductility. The effects of post-consolidation heat treatment are discussed, the preliminary mechanical properties obtained from full-scale turbine disks are presented.

Species Profiles: Life Histories and Environmental Requirements of Coastal Fishes and Invertebrates (South Florida): Gray, Lane, Mutton and Yellowtail Snappers.

DTIC Science & Technology

1986-06-01

pargo prieto, pargo, criollo , vivaneau sorbe (Cervigon pargo dienton, pargo de piedra, 1966, Fisher 1978) pargo moreno, vivaneau sarde grise, aquadera... criollo , Lutjanus 1970-79. Florida landings, analis. Cent. Invest. Pesq. annual summary 1969-1978. U.S. uba. Nota 2:1-16. Natl. Mar. Fish. Serv. Curr

Scoping Report: AI-Driven Wargame Replicator

DTIC Science & Technology

2010-12-01

Evans, 2003 Without training involving external input Responsive to verbal instructions Clark & Karmiloff-Smith, 1993 Associative Rule-based Sloman...Applied to Clustering. Online available on January 21, 2010, at http://laboratorios.fi.uba.ar/lsi/rgm/ comunicaciones /c-AGsclustering-ORLANDO96.pdf...systems for associative recall and recognition. Psychological Review, 91:281-294. [214] Polk, T.A. and Newell, A. (1995). Deduction as verbal reasoning

S. pombe Uba1-Ubc15 Structure Reveals a Novel Regulatory Mechanism of Ubiquitin E2 Activity.

PubMed

Lv, Zongyang; Rickman, Kimberly A; Yuan, Lingmin; Williams, Katelyn; Selvam, Shanmugam Panneer; Woosley, Alec N; Howe, Philip H; Ogretmen, Besim; Smogorzewska, Agata; Olsen, Shaun K

2017-02-16

Ubiquitin (Ub) E1 initiates the Ub conjugation cascade by activating and transferring Ub to tens of different E2s. How Ub E1 cooperates with E2s that differ substantially in their predicted E1-interacting residues is unknown. Here, we report the structure of S. pombe Uba1 in complex with Ubc15, a Ub E2 with intrinsically low E1-E2 Ub thioester transfer activity. The structure reveals a distinct Ubc15 binding mode that substantially alters the network of interactions at the E1-E2 interface compared to the only other available Ub E1-E2 structure. Structure-function analysis reveals that the intrinsically low activity of Ubc15 largely results from the presence of an acidic residue at its N-terminal region. Notably, Ub E2 N termini are serine/threonine rich in many other Ub E2s, leading us to hypothesize that phosphorylation of these sites may serve as a novel negative regulatory mechanism of Ub E2 activity, which we demonstrate biochemically and in cell-based assays. Copyright © 2017 Elsevier Inc. All rights reserved.

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

The plpdfa software is a product of an LDRD project at LLNL entitked "Adaptive Sampling for Very High Throughput Data Streams" (tracking number 11-ERD-035). This software was developed by a graduate student summer intern, Chris Challis, who worked under project PI Dan Merl furing the summer of 2011. The software the source code is implementing is a statistical analysis technique for clustering and classification of text-valued data. The method had been previously published by the PI in the open literature.

Investigation of Field-Collected Data Using Diffuse and Specular, Forward and Reverse Radiative Transfer Models

DTIC Science & Technology

2015-03-26

Statement It is very difficult to obtain and use spectral BRDFs due to aforementioned reasons, while the need to accurately model the spectral and...Lambertian and MERL nickel-shaped BRDF models (Butler, 2014:1- 3 10), suggesting that accurate BRDFs are required to account for the significance of... BRDF -based radiative transfer models . Research Objectives /Hypotheses The need to represent the spectral reflected radiance of a material using

Use of Life Cycle Costing in the Development of Standards

DTIC Science & Technology

1988-12-01

Bringhurst, Mountain Fuel Supply 6. T. Joseph Cardenas, McGraw Hill 7. Sally A. Hooks, EEI 8. Merle F. McBride, Owens - Corning Fiberglas 9. Kenneth D...Stanonik, GAMA 23. Clifford D. Smith, Owens - Corning Fiberglas 24. Chris Thomaidis, Department of Housing & Urban Development 25. Adrian Tuluca, Steven...Professionals, McGraw-Hill Book Company, 1981. 8. Stewart, Rodney D., Cost EstimatinQ, John Wiley & Sons, Inc., 1982. 9. Owens Corning , Telephone

Comprehensive analysis of MHC class I genes from the U-, S-, and Z-lineages in Atlantic salmon.

PubMed

Lukacs, Morten F; Harstad, Håvard; Bakke, Hege G; Beetz-Sargent, Marianne; McKinnel, Linda; Lubieniecki, Krzysztof P; Koop, Ben F; Grimholt, Unni

2010-03-05

We have previously sequenced more than 500 kb of the duplicated MHC class I regions in Atlantic salmon. In the IA region we identified the loci for the MHC class I gene Sasa-UBA in addition to a soluble MHC class I molecule, Sasa-ULA. A pseudolocus for Sasa-UCA was identified in the nonclassical IB region. Both regions contained genes for antigen presentation, as wells as orthologues to other genes residing in the human MHC region. The genomic localisation of two MHC class I lineages (Z and S) has been resolved. 7 BACs were sequenced using a combination of standard Sanger and 454 sequencing. The new sequence data extended the IA region with 150 kb identifying the location of one Z-lineage locus, ZAA. The IB region was extended with 350 kb including three new Z-lineage loci, ZBA, ZCA and ZDA in addition to a UGA locus. An allelic version of the IB region contained a functional UDA locus in addition to the UCA pseudolocus. Additionally a BAC harbouring two MHC class I genes (UHA) was placed on linkage group 14, while a BAC containing the S-lineage locus SAA (previously known as UAA) was placed on LG10. Gene expression studies showed limited expression range for all class I genes with exception of UBA being dominantly expressed in gut, spleen and gills, and ZAA with high expression in blood. Here we describe the genomic organization of MHC class I loci from the U-, Z-, and S-lineages in Atlantic salmon. Nine of the described class I genes are located in the extension of the duplicated IA and IB regions, while three class I genes are found on two separate linkage groups. The gene organization of the two regions indicates that the IB region is evolving at a different pace than the IA region. Expression profiling, polymorphic content, peptide binding properties and phylogenetic relationship show that Atlantic salmon has only one MHC class Ia gene (UBA), in addition to a multitude of nonclassical MHC class I genes from the U-, S- and Z-lineages.

Promising Mid-term Results With a Cup-cage Construct for Large Acetabular Defects and Pelvic Discontinuity.

PubMed

Amenabar, Tomas; Rahman, Wael A; Hetaimish, Bandar M; Kuzyk, Paul R; Safir, Oleg A; Gross, Allan E

2016-02-01

Restoring normal anatomy and achieving stable fixation of the acetabular component can be especially challenging when the surgeon must deal with severe acetabular defects and/or pelvic discontinuity. The cup-cage (CC) construct, where an ilioischial cage is cemented within a biologically fixed porous metal cup, has emerged as an excellent option to treat such challenges. We sought to determine (1) mid-term Kaplan-Meier survival; (2) clinical outcomes based on Merle d'Aubigné-Postel scores; (3) radiological outcomes based primarily on construct migration; and (4) the complication rate for a series of 67 CC procedures performed at our institution. All hip revision procedures between January 2003 and March 2012 where a CC was used (with the exception of tumor cases or acute fracture; four total cases) that had a minimum 2-year followup and that had been seen within the last 2 years were included in this retrospective review. Acetabular bone loss and presence of pelvic discontinuity were assessed according to the Gross classification. Sixty-seven CC procedures with an average followup of 74 months (range, 24-135 months; SD, 34.3) months were identified; 26 of 67 (39%) were Gross Type IV and 41 of 67 (61%) were Gross Type V (pelvic discontinuity). Postoperative clinical and radiological evaluation was done annually. Merle d'Aubigné-Postel scores were recorded and all radiographs were compared with the 6-week postoperative radiographs to evaluate for radiographic loosening or migration. Failure was defined as revision surgery for any cause, including infection. The 5-year Kaplan-Meier survival rate with revision for any cause representing failure was 93% (95% confidence interval [CI], 83.1-97.4), and the 10-year survival rate was 85% (95% CI, 67.2-93.8). The Merle d'Aubigné-Postel score improved significantly from a mean of 6 preoperatively to 13 postoperatively (p < 0.001). Four CC had nonprogressive radiological migration of the ischial flange and they remain stable. We believe that the CC construct is a suitable choice to treat chronic pelvic discontinuity; it also remains a reliable option for the treatment of severe acetabular bone defects if stable fixation cannot be obtained through the use of a trabecular metal cup with or without augments. Level IV, therapeutic study.

Modified porous tantalum rod technique for the treatment of femoral head osteonecrosis

PubMed Central

Pakos, Emilios E; Megas, Panayiotis; Paschos, Nikolaos K; Syggelos, Spyridon A; Kouzelis, Antonios; Georgiadis, Georgios; Xenakis, Theodoros A

2015-01-01

AIM: To study a modified porous tantalum technique for the treatment of osteonecrosis of the femoral head. METHODS: The porous tantalum rod was combined with endoscopy, curettage, autologous bone grafting and use of bone marrow aspirates from iliac crest aspiration in 49 patients (58 hips) with a mean age of 38 years. The majority of the patients had idiopathic osteonecrosis, followed by corticosteroid-induced osteonecrosis. Thirty-eight hips were of Steinberg stage II disease and 20 hips were of stage III disease. Patients were followed for 5 years and were evaluated clinically with the Merle D’Aubigne and Postel score and radiologically. The primary outcome of the study was survival based on the conversion to total hip arthroplasty (THA). Secondary outcomes included deterioration of the osteonecrosis to a higher disease stage at 5 years compared to the preoperative period and identification of factors that were associated with survival. The Kaplan-Meier survival analysis was performed to evaluate the survivorship of the prosthesis, and the Fisher exact test was performed to test associations between various parameters with survival. RESULTS: No patient developed any serious intraoperative or postoperative complication including implant loosening or migration and donor site morbidity. During the 5-year follow up, 1 patient died, 7 patients had disease progression and 4 hips were converted to THA. The 5-year survival based on conversion to THA was 93.1% and the respective rate based on disease progression was 87.9%. Stage II disease was associated with statistically significant better survival rates compared to stage III disease (P = 0.04). The comparison between idiopathic and non-idiopathic osteonecrosis and between steroid-induced and non-steroid-induced osteonecrosis did not showed any statistically significant difference in survival rates. The clinical evaluation revealed statistically significantly improved Merle d’Aubigne scores at 12 mo postoperatively compared to the preoperative period (P < 0.001). The mean preoperative Merle d’Aubigne score was 13.0 (SD: 1.8). The respective score at 12 mo improved to 17.0 (SD: 2.0). The 12-mo mean score was retained at 5 years. CONCLUSION: The modified porous tantalum rod technique presented here showed encouraging outcomes. The survival rates based on conversion to THA are the lowest reported in the published literature. PMID:26601065

Modified porous tantalum rod technique for the treatment of femoral head osteonecrosis.

PubMed

Pakos, Emilios E; Megas, Panayiotis; Paschos, Nikolaos K; Syggelos, Spyridon A; Kouzelis, Antonios; Georgiadis, Georgios; Xenakis, Theodoros A

2015-11-18

To study a modified porous tantalum technique for the treatment of osteonecrosis of the femoral head. The porous tantalum rod was combined with endoscopy, curettage, autologous bone grafting and use of bone marrow aspirates from iliac crest aspiration in 49 patients (58 hips) with a mean age of 38 years. The majority of the patients had idiopathic osteonecrosis, followed by corticosteroid-induced osteonecrosis. Thirty-eight hips were of Steinberg stage II disease and 20 hips were of stage III disease. Patients were followed for 5 years and were evaluated clinically with the Merle D'Aubigne and Postel score and radiologically. The primary outcome of the study was survival based on the conversion to total hip arthroplasty (THA). Secondary outcomes included deterioration of the osteonecrosis to a higher disease stage at 5 years compared to the preoperative period and identification of factors that were associated with survival. The Kaplan-Meier survival analysis was performed to evaluate the survivorship of the prosthesis, and the Fisher exact test was performed to test associations between various parameters with survival. No patient developed any serious intraoperative or postoperative complication including implant loosening or migration and donor site morbidity. During the 5-year follow up, 1 patient died, 7 patients had disease progression and 4 hips were converted to THA. The 5-year survival based on conversion to THA was 93.1% and the respective rate based on disease progression was 87.9%. Stage II disease was associated with statistically significant better survival rates compared to stage III disease (P = 0.04). The comparison between idiopathic and non-idiopathic osteonecrosis and between steroid-induced and non-steroid-induced osteonecrosis did not showed any statistically significant difference in survival rates. The clinical evaluation revealed statistically significantly improved Merle d'Aubigne scores at 12 mo postoperatively compared to the preoperative period (P < 0.001). The mean preoperative Merle d'Aubigne score was 13.0 (SD: 1.8). The respective score at 12 mo improved to 17.0 (SD: 2.0). The 12-mo mean score was retained at 5 years. The modified porous tantalum rod technique presented here showed encouraging outcomes. The survival rates based on conversion to THA are the lowest reported in the published literature.

A Survey of Electric Laser Codes.

DTIC Science & Technology

1983-06-01

709-71M R M> Asset, latcs lirute Maftson (505) 24 J-560’. Northrop R t. T Center William B. Lacina «213) 377-4811 X »62 Lo < kheed... Pulsar Device. ASSESSMENT OF LIMITATIONS: The enerc^ extraction routine is not pasea on physical optics principles, so predictions are of limited...Along Optics] Axis: No i- lo \\c Direction; KO KINETICS MODELED: Pulsed; V CW: _ Nl’MERlCAL SCHEME USED IN RATE CALCULATION i^ I

An Examination of the Effect of External Influences on the Soviet Negotiation Position in Post 1962 Arms Control Agreements

DTIC Science & Technology

1978-06-09

Bolsheviks inherited not only the geography and • natural resources of Russia, but also the people and the his- tory and the culture. While Marxism ...international disarmament, but rather the arming of the proletariat for the purpose of disarming and defeating the bourgeoisie . <hough Maxim Litvinov, the...Drachkovitch, Milorad M, Marxism in the Modern World, Stanford, CA: Stanford University Press, 1965. Fainsod, Merle. How Russia-is Ruled, Cambridges

Atypical anterior wall fracture of the acetabulum: case series of anterior acetabular rim fracture without involvement of the pelvic brim.

PubMed

Lenarz, Christopher J; Moed, Berton R

2007-09-01

The purpose of this study was to describe a form of anterior wall acetabular fracture, which has been inadequately defined in the literature. Retrospective analysis of consecutive patients. Level 1 trauma center. A retrospective analysis of consecutive acetabulum patients treated by a single surgeon between 1999 and 2005 identified 6 patients with a form of anterior wall fracture without involvement of the pelvic brim. All fractures were treated operatively. Open reduction and internal fixation through an anterior surgical approach. Final radiographic appearance and modified Merle d'Aubigne score. All 6 cases demonstrated characteristics of an atypical fracture of the anterior wall, involving the anterior rim of the acetabulum similar in nature to those described for the posterior wall, rather than the standard anterior wall fracture type described by Letournel. Of the 6 cases that were identified, 5 had follow-up 1 year or greater with a mean modified Merle d'Aubigne Score of 17 (range: 17-18). A form of anterior wall acetabular fracture exists, which involves the anterior acetabular rim without involvement of the pelvic brim. It can occur in young patients with high-energy mechanisms of injury, as well as in the elderly with low-energy trauma. With appropriate surgical management, using a modified Smith-Peterson approach, good to excellent clinical outcomes should be expected.

The UbL-UBA Ubiquilin4 protein functions as a tumor suppressor in gastric cancer by p53-dependent and p53-independent regulation of p21.

PubMed

Huang, Shengkai; Li, Yan; Yuan, Xinghua; Zhao, Mei; Wang, Jia; Li, You; Li, Yuan; Lin, Hong; Zhang, Qiao; Wang, Wenjie; Li, Dongdong; Dong, Xin; Li, Lanfen; Liu, Min; Huang, Weiyan; Huang, Changzhi

2018-06-13

Ubiquilin4 (Ubqln4), a member of the UbL-UBA protein family, serves as an adaptor in the degradation of specific substrates via the proteasomal pathway. However, the biological function of Ubqln4 remains largely unknown, especially in cancer. Here, we reported that Ubqln4 was downregulated in gastric cancer tissues and functioned as a tumor suppressor by inhibiting gastric cancer cell proliferation in vivo and in vitro. Overexpression of Ubqln4-induced cellular senescence and G1-S cell cycle arrest in gastric cancer cells and activated the p53/p21 axis. Moreover, Ubqln4 regulated p21 through both p53-dependent and p53-independent manners. Ubqln4 interacted with RNF114, an E3 ubiquitin ligase of p21, and negatively regulated its expression level, which in turn stabilized p21 by attenuating proteasomal degradation of p21. These effects of Ubqln4 were partly abrogated in gastric cancer cells upon silencing of p21. Our findings not only establish the anti-tumor potential of Ubqln4 in gastric cancer but also reveal a role for Ubqln4 in regulation of the cell cycle and cellular senescence via stabilizing p21.

A Study of the Use of Family Practice Physicians in Troop Health Clinics of the MEDDAC (Medical Department Activity), Fort Belvoir, Virginia.

DTIC Science & Technology

1981-04-01

Department. The questionnaire, devised by Major Merle Preble, MD and Colonel Llewellyn Legters , MD, gathered demographic data as well as infor- mation on...that it must surely have 7 evolved from the questionnaire devised by Preble and Legters , for the similarities are too remarkable to be merely a...M.D., and Llewellyn Legters , M.D. "Patient Satisfaction Studies in Ambulatory Patient Care Areas: Comparison of General Medical Clinic to Acute Minor

Microgravity

NASA Image and Video Library

1999-06-29

Christiane Gumera, right, a student at Stanton College Preparatory High School in Jacksonville, AL, examines a protein sample while preparing an experiment for flight on the International Space Station (ISS). Merle Myers, left, a University of California, Irvine, researcher, prepares to quick-freeze protein samples in nitrogen. The proteins are in a liquid nitrogen Dewar. Aboard the ISS, the nitrogen will be allowed to evaporated so the samples thaw and then slowly crystallize. They will be anlyzed after return to Earth. Photo credit: NASA/Marshall Space Flight Center (MSFC)

Air Force Heroes in Vietnam

DTIC Science & Technology

1979-01-01

gave me a little more weight on the brakes. I think I must have been skidding on that steel planking . It was a little bit slick from the dampness. I...have a history of outstanding performance and a unique blend of flying experience and leadership ability. To be the boss of a squadron in combat is...hitting something they wanted to hang on to. it was a vital target and its loss would hurt them." Merl and his backseater, Captain Kevin "Mike" Gilroy

Role of the Neddylation Enzyme Uba3, a New Estrogen Receptor Corepressor, in Breast Cancer

DTIC Science & Technology

2005-09-01

downstream targets Cancer Res 64:8184-8192 (cover article ). *This DOD award is acknowledged in these publications. Presentations 1. Fan M, Park A...www.endoiournals.org/. The final copy edited article can be found at 15 http://www.endojoumals.org/. The Endocrine Society disclaims any responsibility or...8217Hutnan Cancer Genetics Program, Departtent of Molecular Virology, Inmunology , and Medical Genetics, Comprehensive Cancer Center, The Ohio State Universit

Effects of Carbon Dioxide and UBA-Like Breathing Resistance on Exercise Endurance

DTIC Science & Technology

2010-04-01

hemoglobin saturation in healthy subjects and dissolved oxygen at atmospheric pressure contributes little to total oxygen transport, anaerobic threshold and...resistance of their breathing circuit is minimal increase VE both at rest and during mild to moderate (below ventilatory threshold ) exercise.2–8...of fatigue for one hour, after which we stopped him. Data for Phase 2 also are reported for only ten of the twelve subjects. We disregarded all

Genotypes of predomestic horses match phenotypes painted in Paleolithic works of cave art.

PubMed

Pruvost, Melanie; Bellone, Rebecca; Benecke, Norbert; Sandoval-Castellanos, Edson; Cieslak, Michael; Kuznetsova, Tatyana; Morales-Muñiz, Arturo; O'Connor, Terry; Reissmann, Monika; Hofreiter, Michael; Ludwig, Arne

2011-11-15

Archaeologists often argue whether Paleolithic works of art, cave paintings in particular, constitute reflections of the natural environment of humans at the time. They also debate the extent to which these paintings actually contain creative artistic expression, reflect the phenotypic variation of the surrounding environment, or focus on rare phenotypes. The famous paintings "The Dappled Horses of Pech-Merle," depicting spotted horses on the walls of a cave in Pech-Merle, France, date back ~25,000 y, but the coat pattern portrayed in these paintings is remarkably similar to a pattern known as "leopard" in modern horses. We have genotyped nine coat-color loci in 31 predomestic horses from Siberia, Eastern and Western Europe, and the Iberian Peninsula. Eighteen horses had bay coat color, seven were black, and six shared an allele associated with the leopard complex spotting (LP), representing the only spotted phenotype that has been discovered in wild, predomestic horses thus far. LP was detected in four Pleistocene and two Copper Age samples from Western and Eastern Europe, respectively. In contrast, this phenotype was absent from predomestic Siberian horses. Thus, all horse color phenotypes that seem to be distinguishable in cave paintings have now been found to exist in prehistoric horse populations, suggesting that cave paintings of this species represent remarkably realistic depictions of the animals shown. This finding lends support to hypotheses arguing that cave paintings might have contained less of a symbolic or transcendental connotation than often assumed.

Hypertrophy of the tensor fascia lata muscle as a complication of total hip arthroplasty.

PubMed

Rodríguez-Roiz, Juan Miguel; Bori, Guillem; Tomas, Xavier; Fernández-Valencia, Jenaro A; García-Díez, Ana Isabel; Pomés, Jaume; Garcia, Sebastián

2017-02-01

Hypertrophy of the tensor fascia lata muscle (HTFLM) is a rare complication after total hip arthroplasty (THA) and is a potential source of pain, palpable mass, or both. We retrospectively analyzed 1285 primary THAs and 482 THA revisions (THAR) performed at our center from 2008 to 2014. Among these, five patients had HTFLM (average age 68.8 years). The type of surgery and symptoms were evaluated, as were imaging studies (CT or MRI) of both hips (10 hips), and functional outcomes with the Merle d'Aubigné score. The suspected diagnosis was established at an average of 30.2 months after surgery. Four cases occurred after THA and one case after THAR. A modified Hardinge approach was used in four cases and a Röttinger approach in one case. Two cases had pain and palpable mass in the trochanteric region and three cases only pain. The asymmetric HTFLM of the THA side against the nonsurgical side was confirmed by measuring the cross section of the tensor fascia lata muscle on imaging. The sartorius muscle was measured for reference in each case. The Merle d'Aubigne scale had a mean value of 16.6 (range 13-18) at 38 months after the procedure. HTFLM after THA is a benign condition that could be mistaken for a tumor when presenting as a palpable mass. We propose that it should be considered in the differential diagnosis of pain in the lateral aspect of hips that have previously undergone THA.

Genotypes of predomestic horses match phenotypes painted in Paleolithic works of cave art

PubMed Central

Pruvost, Melanie; Bellone, Rebecca; Benecke, Norbert; Sandoval-Castellanos, Edson; Cieslak, Michael; Kuznetsova, Tatyana; Morales-Muñiz, Arturo; O'Connor, Terry; Reissmann, Monika; Hofreiter, Michael; Ludwig, Arne

2011-01-01

Archaeologists often argue whether Paleolithic works of art, cave paintings in particular, constitute reflections of the natural environment of humans at the time. They also debate the extent to which these paintings actually contain creative artistic expression, reflect the phenotypic variation of the surrounding environment, or focus on rare phenotypes. The famous paintings “The Dappled Horses of Pech-Merle,” depicting spotted horses on the walls of a cave in Pech-Merle, France, date back ∼25,000 y, but the coat pattern portrayed in these paintings is remarkably similar to a pattern known as “leopard” in modern horses. We have genotyped nine coat-color loci in 31 predomestic horses from Siberia, Eastern and Western Europe, and the Iberian Peninsula. Eighteen horses had bay coat color, seven were black, and six shared an allele associated with the leopard complex spotting (LP), representing the only spotted phenotype that has been discovered in wild, predomestic horses thus far. LP was detected in four Pleistocene and two Copper Age samples from Western and Eastern Europe, respectively. In contrast, this phenotype was absent from predomestic Siberian horses. Thus, all horse color phenotypes that seem to be distinguishable in cave paintings have now been found to exist in prehistoric horse populations, suggesting that cave paintings of this species represent remarkably realistic depictions of the animals shown. This finding lends support to hypotheses arguing that cave paintings might have contained less of a symbolic or transcendental connotation than often assumed. PMID:22065780

Role of the Neddylation Enzyme Uba3, A New Estrogen Receptor Corepressor in Breast Cancer

DTIC Science & Technology

2006-09-01

cells acquire ICI 182,780 resistance while retaining expres- sion of ER. MATERIALS AND METHODS Materials The following antibodies and reagents were used...protein assay kit; FBS and csFBS (Hy- Clone Laboratories, Inc., Logan, UT); LipofectAMINE Plus Reagent , geneticin, and other cell culture reagents were...plasmid DNA (adjusted by corresponding empty vectors) by using LipofectAMINE Plus Reagent according to the manufacturer’s guidelines. Five hours later

Formulation of Subgrid Variability and Boundary-Layer Cloud Cover in Large-Scale Models

DTIC Science & Technology

1999-02-28

related to burned and unburned landscapes, saline and non-saline soils, and irrigated and nonirrigated crops. Escuela de Agrono’mia Universidad de Talca...Piso 2 Departamento de Ciencias de la Atmosfera 1428 Capital Federal ARGENTINA Juan Carlos TORRES, torres@cima.uba.ar Coupled land-surface...evaporation fraction, and qc,sat is the canopy saturation specific humidity, a function of Tc. Using (21) - (22) we then de - termine qc qc = qca

Dissection of Swa2p/Auxilin Domain Requirements for Cochaperoning Hsp70 Clathrin-uncoating Activity In Vivo

PubMed Central

Xiao, Jing; Kim, Leslie S.

2006-01-01

The auxilin family of J-domain proteins load Hsp70 onto clathrin-coated vesicles (CCVs) to drive uncoating. In vitro, auxilin function requires its ability to bind clathrin and stimulate Hsp70 ATPase activity via its J-domain. To test these requirements in vivo, we performed a mutational analysis of Swa2p, the yeast auxilin ortholog. Swa2p is a modular protein with three N-terminal clathrin-binding (CB) motifs, a ubiquitin association (UBA) domain, a tetratricopeptide repeat (TPR) domain, and a C-terminal J-domain. In vitro, clathrin binding is mediated by multiple weak interactions, but a Swa2p truncation lacking two CB motifs and the UBA domain retains nearly full function in vivo. Deletion of all CB motifs strongly abrogates clathrin disassembly but does not eliminate Swa2p function in vivo. Surprisingly, mutation of the invariant HPD motif within the J-domain to AAA only partially affects Swa2p function. Similarly, a TPR point mutation (G388R) causes a modest phenotype. However, Swa2p function is abolished when these TPR and J mutations are combined. The TPR and J-domains are not functionally redundant because deletion of either domain renders Swa2p nonfunctional. These data suggest that the TPR and J-domains collaborate in a bipartite interaction with Hsp70 to regulate its activity in clathrin disassembly. PMID:16687570

Disturbance of proteasomal and autophagic protein degradation pathways by amyotrophic lateral sclerosis-linked mutations in ubiquilin 2.

PubMed

Osaka, Mayuko; Ito, Daisuke; Suzuki, Norihiro

2016-04-01

Ubiquilin (UBQLN), a member of the ubiquitin-like (UBL)-ubiquitin-associated (UBA) family, is a dual regulator of both the proteasomal and autophagic branches of the cellular protein degradation system. Mutations in the UBQLN2 gene encoding ubiquilin 2 cause X-linked amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD), and UBQLN2-positive inclusions have been identified in ALS patients with UBQLN2 mutations as well as in cases of both familial and sporadic ALS without UBQLN2 mutations. Compelling evidence links UBQLN2 to disturbance of the protein quality control network in neurons, but the pathomechanisms remain obscure. This study aimed to clarify how ALS-linked mutations in UBQLN2 affect the protein degradation system. Overexpression of a UBQLN2 with ALS-associated mutations resulted in the accumulation of polyubiquitinated proteins in neuronal cells, including the ALS-associated protein TDP-43. This effect was dependent on the UBA domain but not on inclusion formation. Immunocytochemistry and protein fractionation analysis of IVm-UBQLN2 cellular distribution indicated that it sequesters ubiquitinated substrates from both the proteasomal and autophagic branches of the protein degradation system, resulting in accumulation of polyubiquitinated substrates. These findings provide a molecular basis for the development of ALS/FTD-associated proteinopathy and establish novel therapeutic targets for ALS. Copyright © 2016. Published by Elsevier Inc.

Identification of stably expressed reference genes for RT-qPCR data normalization in defined localizations of cyclic bovine ovaries.

PubMed

Schoen, K; Plendl, J; Gabler, C; Kaessmeyer, S

2015-06-01

Ovaries are highly complex organs displaying morphological, molecular and functional differences between their cortical zona parenchymatosa and medullary zona vasculosa, and also between the different cyclic luteal stages. Objective of the present study was to validate expression stability of twelve putative reference genes (RGs) in bovine ovaries, considering the intrinsic heterogeneity of bovine ovarian tissue with regard to different luteal stages and intra-ovarian localizations. The focus was on identifying RGs, which are suitable to normalize RT-qPCR results of ovaries collected from clinical healthy cattle, irrespective of localization and the hormonal stage. Expression profiles of twelve potential reference genes (GAPDH, ACTB, YWHAZ, HPRT1, SDHA, UBA52, POLR2C, RPS9, ACTG2, H3F3B, RPS18 and RPL19) were analysed. Evaluation of gene expression differences was performed using genorm, normfinder, and bestkeeper software. The most stably expressed genes according to genorm, normfinder and bestkeeper approaches contained the candidates H3F3B, RPS9, YWHAZ, RPS18, POLR2C and UBA52. Of this group, the genes YWHAZ, H3F3B and RPS9 could be recommended as best-suited RGs for normalization purposes on healthy bovine ovaries irrespective of the luteal stage or intra-ovarian localization. © 2014 Blackwell Verlag GmbH.

Student Pave Way for First Microgravity Experiments on International Space Station

NASA Technical Reports Server (NTRS)

1999-01-01

Christiane Gumera, right, a student at Stanton College Preparatory High School in Jacksonville, AL, examines a protein sample while preparing an experiment for flight on the International Space Station (ISS). Merle Myers, left, a University of California, Irvine, researcher, prepares to quick-freeze protein samples in nitrogen. The proteins are in a liquid nitrogen Dewar. Aboard the ISS, the nitrogen will be allowed to evaporated so the samples thaw and then slowly crystallize. They will be anlyzed after return to Earth. Photo credit: NASA/Marshall Space Flight Center (MSFC)

U S Navy Diving Manual. Volume 2. Mixed-Gas Diving. Revision 1.

DTIC Science & Technology

1981-07-01

has been soaked in a solution of portant aspects of underwater physics and physiology caustic potash. This chemical absorbed the carbon as they...between the diver’s breathing passages and the circuit must be of minimum volume minimum of caustic fumes. Water produced by the to preclude deadspace and...strongly react with water to pro- space around the absorbent bed to reduce the gas duce caustic fumes and cannot be used in UBA’s. flow distance. The

Role of the Neddylation Enzyme Uba3, A New Estrogen Receptor Corepressor, in Breast Cancer

DTIC Science & Technology

2005-05-01

Nawaz Z, Lonard DM, Dennis AP, Smith CL, O’Malley BW position 3997, within the intron); reverse primer, 5’- ACCA - 1999 Proteasome-dependent degradation of...ERE) and control reporter constructs for the functional analyses of ERa. could account for this discrepancy. In the present study, an estrogen...pathways. Huang). The costs of publication of this article were defrayed in part by the payment of page In this study, we investigated whether the removal

Decompression from He-N2-O2 (TRIMIX) Bounce Dives Is Not More Efficient Than From He-O2 (HELIOX) Bounce Dives

DTIC Science & Technology

2015-05-28

Diver Characteristics Appendix E Diving Schedule Appendix F Medical Incidents Appendix G UBA Gas Compositions iv ACKNOWLEDGEMENTS The...experimental dives (median = 3). The schedule of each diver’s participation in experimental dives is given in Appendix E . Divers were required to avoid any...divers’ participation on each test schedule is given in Appendix E . The numbers of completed man-dives on the two schedules are not multiples of the

Early Versus Late Weight-Bearing Protocols for Surgically Managed Posterior Wall Acetabular Fractures.

PubMed

Heare, Austin; Kramer, Nicholas; Salib, Christopher; Mauffrey, Cyril

2017-07-01

Despite overall improved outcomes with open reduction and internal fixation of acetabular fractures, posterior wall fractures show disproportionately poor results. The effect of weight bearing on outcomes of fracture management has been investigated in many lower extremity fractures, but evidence-based recommendations in posterior wall acetabular fractures are lacking. The authors systematically reviewed the current literature to determine if a difference in outcome exists between early and late postoperative weight-bearing protocols for surgically managed posterior wall acetabular fractures. PubMed and MEDLINE were searched for posterior wall acetabular fracture studies that included weight-bearing protocols and Merle d'Aubigné functional scores. Twelve studies were identified. Each study was classified as either early or late weight bearing. Early weight bearing was defined as full, unrestricted weight bearing at or before 12 weeks postoperatively. Late weight bearing was defined as restricted weight bearing for greater than 12 weeks postoperatively. The 2 categories were then compared by functional score using a 2-tailed t test and by complication rate using chi-square analysis. Six studies (152 fractures) were placed in the early weight-bearing category. Six studies (302 fractures) were placed in the late weight-bearing category. No significant difference in Merle d'Aubigné functional scores was found between the 2 groups. No difference was found regarding heterotopic ossification, avascular necrosis, superficial infections, total infections, or osteoarthritis. This systematic review found no difference in functional outcome scores or complication rates between early and late weight-bearing protocols for surgically treated posterior wall fractures. [Orthopedics. 2017: 40(4):e652-e657.]. Copyright 2017, SLACK Incorporated.

Treatment of protrusio fractures of the acetabulum in patients 70 years and older.

PubMed

Archdeacon, Michael T; Kazemi, Namdar; Collinge, Cory; Budde, Bradley; Schnell, Scott

2013-05-01

To present clinical, radiographic, and functional outcomes in patients 70 years and older with a protrusio-type acetabulum fracture. Retrospective case series. Two level 1 trauma centers. Between November 2000 and December 2009, 39 consecutive patients older than 70 years with protrusio acetabulum fractures were enrolled. Open reduction internal fixation using a combination of pelvic brim and infrapectineal plates. Clinical, radiographic, and functional outcomes as assessed with the modified Merle d'Aubigné score. Twelve patients were lost to follow-up (<12 months), and one patient was excluded from analysis because he was treated with a percutaneous technique. The remaining 26 (67%) had a mean follow-up of 34 months (12-127 months). At the final follow-up, radiographic grades were excellent in 15, good in 3, poor in 3, and 5 patients had a total hip arthroplasty (19%) at an average of 18 months after the index procedure .The average modified Merle d'Aubigné score was 16 (9-18); categorized as excellent in 10, very good in 4, good in 7, fair in 2, and poor in 3. In the senior patient with a protrusio acetabulum fracture, a treatment strategy that optimizes preoperative conditions, minimizes operative time and blood loss, achieves a stable concentric hip joint, and encourages immediate postoperative ambulation can result in reasonable clinical, radiographic, and functional outcomes with acceptable morbidity. This appears to remain true even in the face of a less than anatomic reduction. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Periacetabular Osteotomy Provides Higher Survivorship Than Rim Trimming for Acetabular Retroversion.

PubMed

Zurmühle, Corinne A; Anwander, Helen; Albers, Christoph E; Hanke, Markus S; Steppacher, Simon D; Siebenrock, Klaus A; Tannast, Moritz

2017-04-01

Acetabular retroversion can cause impaction-type femoroacetabular impingement leading to hip pain and osteoarthritis. It can be treated by anteverting periacetabular osteotomy (PAO) or acetabular rim trimming with refixation of the labrum. There is increasing evidence that acetabular retroversion is a rotational abnormality of the entire hemipelvis and not a focal overgrowth of the anterior acetabular wall, which favors an anteverting PAO. However, it is unknown if this larger procedure would be beneficial in terms of survivorship and Merle d'Aubigné scores in a midterm followup compared with rim trimming. We asked if anteverting PAO results in increased survivorship of the hip compared with rim trimming through a surgical hip dislocation in patients with symptomatic acetabular retroversion. We performed a retrospective, comparative study evaluating the midterm survivorship of two matched patient groups with symptomatic acetabular retroversion undergoing either anteverting PAO or acetabular rim trimming through a surgical hip dislocation. Acetabular retroversion was defined by a concomitantly present positive crossover, posterior wall, and ischial spine sign. A total of 279 hips underwent a surgical intervention for acetabular retroversion at our center between 1997 and 2012 (166 periacetabular osteotomies, 113 rim trimmings through surgical hip dislocation). A total of 99 patients (60%) were excluded from the PAO group and 56 patients (50%) from the rim trimming group because they had any of several prespecified conditions (eg, dysplasia or pediatric conditions 61 [37%] for the PAO group and two [2%] for the rim trimming group), matching (10 [6%]/10 [9%] hips), deficient records (10 [6%]/13 [12%] hips), or the patient declined or was lost to followup (18 [11%]/31 [27%] hips). This left 67 hips (57 patients) that underwent anteverting PAO and 57 hips (52 patients) that had acetabular rim trimming. The two groups did not differ in terms of age, sex, body mass index, preoperative ROM, preoperative Merle d'Aubigné-Postel score, radiographic morphology of the acetabulum (except total and anterior acetabular coverage), alpha angle, Tönnis grade of osteoarthritis, and labral and chondral lesions on the preoperative MRI. During the period in question, we generally performed PAO from 1997 to 2003. With the availability of surgical hip dislocation and labral refixation, we generally performed rim trimming from 2004 to 2010. With growing knowledge of the underlying pathomorphology, anteverting PAOs became more common again around 2007 to 2008. A minimum followup of 2 years was required for this study. Failures were included at any time. The median followup for the anteverting PAO group was 9.5 years (range, 2-17.4 years) and 6.8 years (range, 2.2-10.5 years) for the rim trimming group (p < 0.001). Kaplan-Meier survivorship analysis was performed using the following endpoints at 5 and 10 years: THA, radiographic progression of osteoarthritis by one Tönnis grade, and/or Merle d'Aubigné-Postel score < 15 points. Although the 5-year survivorship of the two groups was not different with the numbers available (86% [95% confidence interval {CI}, 76%-94%] for anteverting PAO versus 86% [95% CI, 76%-96%] for acetabular rim trimming), we found increased survivorship at 10 years in hips undergoing anteverting PAO for acetabular retroversion (79% [95% CI, 68%-90%]) compared with acetabular rim trimming (23% [95% CI, 6%-40%]) at 10 years (p < 0.001). The drop in the survivorship curve for the acetabular rim trimming through surgical hip dislocation group started at Year 6. The main reason for failure was a decreased Merle d'Aubigné score. Anteverting PAO may be the more appropriate treatment for hips with substantial acetabular retroversion. This may be the result of reduction of an already smaller lunate surface of hips with acetabular retroversion through rim trimming. However, rim trimming may still benefit hips with acetabular retroversion in which only one or two of the three signs are positive. Future randomized studies should compare these treatments. Level III, therapeutic study.

Precision of Four Acoustic Bone Measurement Devices

NASA Technical Reports Server (NTRS)

Miller, Christopher; Feiveson, Alan H.; Shackelford, Linda; Rianon, Nahida; LeBlanc, Adrian

2000-01-01

Though many studies have quantified the precision of various acoustic bone measurement devices, it is difficult to directly compare the results among the studies, because they used disparate subject pools, did not specify the estimation methodology, or did not use consistent definitions for various precision characteristics. In this study, we used a repeated measures design protocol to directly determine the precision characteristics of four acoustic bone measurement devices: the Mechanical Response Tissue Analyzer (MRTA), the UBA-575+, the SoundScan 2000 (S2000), and the Sahara Ultrasound Done Analyzer. Ten men and ten women were scanned on all four devices by two different operators at five discrete time points: Week 1, Week 2, Week 3, Month 3 and Month 6. The percent coefficient of variation (%CV) and standardized coefficient of variation were computed for the following precision characteristics: interoperator effect, operator-subject interaction, short-term error variance, and long-term drift, The MRTA had high interoperator errors for its ulnar and tibial stiffness measures and a large long-term drift in its tibial stiffness measurement. The UBA-575+ exhibited large short-term error variances and long-term drift for all three of its measurements. The S2000's tibial speed of sound measurement showed a high short-term error variance and a significant operator-subject interaction but very good values ( < 1%) for the other precision characteristics. The Sahara seemed to have the best overall performance, but was hampered by a large %CV for short-term error variance in its broadband ultrasound attenuation measure.

Activation of JNK and IRE1 is critically involved in tanshinone I-induced p62 dependent autophagy in malignant pleural mesothelioma cells: implication of p62 UBA domain

PubMed Central

Yoon, Sangwook; Won, Gunho; Kim, Chang Geun; Jung, Ji Hoon; Kim, Sung-Hoon

2017-01-01

The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells. Furthermore, autophagy flux was enhanced in Tan I-treated H28 cells transfected by RFP-GFP-LC3 constructs, with colocalization of GFP-LC3 punctae with LAMP1 or Lysotracker. Interestingly, C-terminal UBA domain is required for Tan 1 induced aggregation of p62 in H28 cells. Notably, Tan I upregulated CCAAT-enhancer-binding protein homologous protein (CHOP), inositol-requiring protein-1 (IRE1) and p-c-Jun N-terminal kinase (p-JNK), but silencing of IRE1 or p62 and JNK inhibitor SP600125 blocked the LC3II accumulation in Tan I-treated H28 cells. Overall, these findings demonstrate that Tan I exerts antitumor activity through a compromise between apoptosis and p62/SQSTM1-dependent autophagy via activation of JNK and IRE 1 in malignant mesothelioma cells. PMID:28212571

Activation of JNK and IRE1 is critically involved in tanshinone I-induced p62 dependent autophagy in malignant pleural mesothelioma cells: implication of p62 UBA domain.

PubMed

Lee, Jihyun; Sohn, Eun Jung; Yoon, Sangwook; Won, Gunho; Kim, Chang Geun; Jung, Ji Hoon; Kim, Sung-Hoon

2017-04-11

The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells. Furthermore, autophagy flux was enhanced in Tan I-treated H28 cells transfected by RFP-GFP-LC3 constructs, with colocalization of GFP-LC3 punctae with LAMP1 or Lysotracker. Interestingly, C-terminal UBA domain is required for Tan 1 induced aggregation of p62 in H28 cells. Notably, Tan I upregulated CCAAT-enhancer-binding protein homologous protein (CHOP), inositol-requiring protein-1 (IRE1) and p-c-Jun N-terminal kinase (p-JNK), but silencing of IRE1 or p62 and JNK inhibitor SP600125 blocked the LC3II accumulation in Tan I-treated H28 cells. Overall, these findings demonstrate that Tan I exerts antitumor activity through a compromise between apoptosis and p62/SQSTM1-dependent autophagy via activation of JNK and IRE 1 in malignant mesothelioma cells.

Precision of Four Acoustic Bone Measurement Devices

NASA Technical Reports Server (NTRS)

Miller, Christopher; Rianon, Nahid; Feiveson, Alan; Shackelford, Linda; LeBlanc, Adrian

2000-01-01

Though many studies have quantified the precision of various acoustic bone measurement devices, it is difficult to directly compare the results among the studies, because they used disparate subject pools, did not specify the estimation methodology, or did not use consistent definitions for various precision characteristics. In this study, we used a repeated measures design protocol to directly determine the precision characteristics of four acoustic bone measurement devices: the Mechanical Response Tissue Analyzer (MRTA), the UBA-575+, the SoundScan 2000 (S2000), and the Sahara Ultrasound Bone Analyzer. Ten men and ten women were scanned on all four devices by two different operators at five discrete time points: Week 1, Week 2, Week 3, Month 3 and Month 6. The percent coefficient of variation (%CV) and standardized coefficient of variation were computed for the following precision characteristics: interoperator effect, operator-subject interaction, short-term error variance, and long-term drift. The MRTA had high interoperator errors for its ulnar and tibial stiffness measures and a large long-term drift in its tibial stiffness measurement. The UBA-575+ exhibited large short-term error variances and long-term drift for all three of its measurements. The S2000's tibial speed of sound measurement showed a high short-term error variance and a significant operator-subject interaction but very good values (less than 1%) for the other precision characteristics. The Sahara seemed to have the best overall performance, but was hampered by a large %CV for short-term error variance in its broadband ultrasound attenuation measure.

Archaeal Tuc1/Ncs6 Homolog Required for Wobble Uridine tRNA Thiolation Is Associated with Ubiquitin-Proteasome, Translation, and RNA Processing System Homologs

PubMed Central

Chavarria, Nikita E.; Hwang, Sungmin; Cao, Shiyun; Fu, Xian; Holman, Mary; Elbanna, Dina; Rodriguez, Suzanne; Arrington, Deanna; Englert, Markus; Uthandi, Sivakumar; Söll, Dieter; Maupin-Furlow, Julie A.

2014-01-01

While cytoplasmic tRNA 2-thiolation protein 1 (Tuc1/Ncs6) and ubiquitin-related modifier-1 (Urm1) are important in the 2-thiolation of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) at wobble uridines of tRNAs in eukaryotes, the biocatalytic roles and properties of Ncs6/Tuc1 and its homologs are poorly understood. Here we present the first report of an Ncs6 homolog of archaea (NcsA of Haloferax volcanii) that is essential for maintaining cellular pools of thiolated tRNALys UUU and for growth at high temperature. When purified from Hfx. volcanii, NcsA was found to be modified at Lys204 by isopeptide linkage to polymeric chains of the ubiquitin-fold protein SAMP2. The ubiquitin-activating E1 enzyme homolog of archaea (UbaA) was required for this covalent modification. Non-covalent protein partners that specifically associated with NcsA were also identified including UbaA, SAMP2, proteasome activating nucleotidase (PAN)-A/1, translation elongation factor aEF-1α and a β-CASP ribonuclease homolog of the archaeal cleavage and polyadenylation specificity factor 1 family (aCPSF1). Together, our study reveals that NcsA is essential for growth at high temperature, required for formation of thiolated tRNALys UUU and intimately linked to homologs of ubiquitin-proteasome, translation and RNA processing systems. PMID:24906001

Archaeal Tuc1/Ncs6 homolog required for wobble uridine tRNA thiolation is associated with ubiquitin-proteasome, translation, and RNA processing system homologs.

PubMed

Chavarria, Nikita E; Hwang, Sungmin; Cao, Shiyun; Fu, Xian; Holman, Mary; Elbanna, Dina; Rodriguez, Suzanne; Arrington, Deanna; Englert, Markus; Uthandi, Sivakumar; Söll, Dieter; Maupin-Furlow, Julie A

2014-01-01

While cytoplasmic tRNA 2-thiolation protein 1 (Tuc1/Ncs6) and ubiquitin-related modifier-1 (Urm1) are important in the 2-thiolation of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) at wobble uridines of tRNAs in eukaryotes, the biocatalytic roles and properties of Ncs6/Tuc1 and its homologs are poorly understood. Here we present the first report of an Ncs6 homolog of archaea (NcsA of Haloferax volcanii) that is essential for maintaining cellular pools of thiolated tRNA(Lys)UUU and for growth at high temperature. When purified from Hfx. volcanii, NcsA was found to be modified at Lys204 by isopeptide linkage to polymeric chains of the ubiquitin-fold protein SAMP2. The ubiquitin-activating E1 enzyme homolog of archaea (UbaA) was required for this covalent modification. Non-covalent protein partners that specifically associated with NcsA were also identified including UbaA, SAMP2, proteasome activating nucleotidase (PAN)-A/1, translation elongation factor aEF-1α and a β-CASP ribonuclease homolog of the archaeal cleavage and polyadenylation specificity factor 1 family (aCPSF1). Together, our study reveals that NcsA is essential for growth at high temperature, required for formation of thiolated tRNA(Lys)UUU and intimately linked to homologs of ubiquitin-proteasome, translation and RNA processing systems.

Experimentally validated modification to Cook-Torrance BRDF model for improved accuracy

NASA Astrophysics Data System (ADS)

Butler, Samuel D.; Ethridge, James A.; Nauyoks, Stephen E.; Marciniak, Michael A.

2017-09-01

The BRDF describes optical scatter off realistic surfaces. The microfacet BRDF model assumes geometric optics but is computationally simple compared to wave optics models. In this work, MERL BRDF data is fitted to the original Cook-Torrance microfacet model, and a modified Cook-Torrance model using the polarization factor in place of the mathematically problematic cross section conversion and geometric attenuation terms. The results provide experimental evidence that this modified Cook-Torrance model leads to improved fits, particularly for large incident and scattered angles. These results are expected to lead to more accurate BRDF modeling for remote sensing.

[Coat color in dogs. 2: Clinical significance].

PubMed

Laukner, A

1998-04-01

The meaning of the coat colour of the dog reaches further than only to the field of breeding for beauty. Besides aspects of destination (hunting dogs, herding dogs) the clinical meaning is of particular interest. Some colours can show certain defects. Diseases of allowed colours are the colour dilution alopecia (CDA) in diluted (mostly "blue") pigmentation with its subtype of Black hair follicular dysplasia (BHFD) in black pigmentation and congenital deafness in extreme piebalds. Not allowed coat colours, which are connected with defects, are the extreme dapple of the Merle-syndrome and the "grey" Collie with cyclic hematopoesis.

International Conference on Electronic Properties of Two-Dimensional Systems (5th) Held at Oxford, England on 5-9 September 1983.

DTIC Science & Technology

1983-01-01

0 .4 I. -" PREFACE -2k This Volume contains unrefereed manuscripts scheduled for presentation at the Fifth International Conference on Electronic...Stradling July 1983 i____ -__ - INTERNATIONAL DVISORY COMMITTEE T AndO Isu Uba G rda. hinich L Esaki. Yor ktown Heights H Fukeyama, Tokyo C C Grims, SellI Lab...vidth of the absorption line-shope Ie pp1..- n.trrpretstin ot (2.8) is that the interne excited state The mess-shItE and the line-width of the

Ferromagnetic Long Range Ordering in Copper(2) Maleate Monohydrate.

DTIC Science & Technology

1988-11-20

thanks the Consejo Nacional de Ciencia y Tecnologia for a partial fellowship. 10 References 1a) SYNTHECO, Inc., 1920 Industrial Pike, Gastonia, N.C...Philadelphia, 1966; Chapter 3. 14) D. B. Losee and W. E. Hatfield, Phs e.i Q 1122 (1974). 15) y . Yamamoto, M. Matsuura, and T. Haseda, J. Phys.-Soc...Mal in the solid state recorded at room temperature. 12 (0 Vj) N 4W +C +~ 13 4P4 CYC CS) (SG) CS + 0 (0 + C, S+ + 06 + + + 3 CC, (( Y ) uo p1 3ubA 00 CL

[History from neuropsychology to cognitive neurosciences in Argentina].

PubMed

Allegri, Ricardo F; Bagnatti, Pablo

2017-11-01

The first step from the neuropsychology in Argentina was in 1883 with the thesis of Antonio Piñeiro about the brain localization of the language and vision disorders, only few years after Broca. The aim of this work has been to describe the development of the neuropsychology in Argentina and its relation with the psychology, neurology and psychiatry. The first period was into the neurology with its French school in?uence. In 1907, Jose Ingeniero published in French his book about "amusia", Cristofredo Jakob the "folia neurobiologica" where he described the organization of the human brain, Vicente Dimitri in 1933 his book "aphasia" and Bernardo de Quiros in 1959 his works about dyslexia. The psychiatry at the hospices with the German influence from Jakob developed to the modern neuropsychiatry with Juan Carlos Goldar. The argentine school of psychology by the holism and the psychoanalysis influence do not accept the neuropsychology until 1960 where was included at the school of psychology from the university of Buenos Aires (UBA) with the first linguistics works of Juan Azcoaga. At the 80, began the North American influence of the neurology with authors like Carlos Mangone (dementia), Ramon Leiguarda (apraxia), Sergio Starkstein (depression and apathy) and Ricardo Allegri (memory and Alzheimer). In 1982 the Argentine Neuropsychological Society was founded and in 1987 was the working group of dementia from the Argentine Neurological Society. At this moment, Aldo Ferreres organized the chair of neuropsychology at the school of psychology (UBA). Nowadays, the growing as discipline is in context of the psychology, neurology and psychiatry in the way of the recent cognitive neurosciences.

Pharmaceuticals in the environment: scientific evidence of risks and its regulation

PubMed Central

Küster, Anette; Adler, Nicole

2014-01-01

During the past two decades scientists, regulatory agencies and the European Commission have acknowledged pharmaceuticals to be an emerging environmental problem. In parallel, a regulatory framework for environmental risk assessment (ERA) of pharmaceutical products has been developed. Since the regulatory guidelines came into force the German Federal Agency (UBA) has been evaluating ERAs for human and veterinary pharmaceutical products before they are marketed. The results show that approximately 10% of pharmaceutical products are of note regarding their potential environmental risk. For human medicinal products, hormones, antibiotics, analgesics, antidepressants and antineoplastics indicated an environmental risk. For veterinary products, hormones, antibiotics and parasiticides were most often discussed as being environmentally relevant. These results are in good correlation with the results within the open scientific literature of prioritization approaches for pharmaceuticals in the environment. UBA results revealed that prospective approaches, such as ERA of pharmaceuticals, play an important role in minimizing problems caused by pharmaceuticals in the environment. However, the regulatory ERA framework could be improved by (i) inclusion of the environment in the risk–benefit analysis for human pharmaceuticals, (ii) improvement of risk management options, (iii) generation of data on existing pharmaceuticals, and (iv) improving the availability of ERA data. In addition, more general and integrative steps of regulation, legislation and research have been developed and are presented in this article. In order to minimize the quantity of pharmaceuticals in the environment these should aim to (i) improve the existing legislation for pharmaceuticals, (ii) prioritize pharmaceuticals in the environment and (iii) improve the availability and collection of pharmaceutical data. PMID:25405974

The assemblage composition and structure of swimming crabs (Portunoidea) in continental shelf waters of southeastern Brazil

NASA Astrophysics Data System (ADS)

Andrade, L. S.; Frameschi, I. F.; Costa, R. C.; Castilho, A. L.; Fransozo, A.

2015-02-01

Three regions along the Brazilian coast characterized by the occurrence of contrasting natural phenomena, such as upwellings and continental input, were surveyed to determine the composition and structure of the assemblage of swimming crabs. Twelve monthly collections were undertaken (July 2010 to June 2011) in Macaé, Rio de Janeiro (MAC); Ubatuba, São Paulo (UBA); and São Francisco do Sul, Santa Catarina (SFS). The lowest values ​​of the phi sediment grain size measure, bottom temperature and the highest values of organic matter and salinity were measured in MAC. In all, 10,686 individuals were collected, belonging to six species of Portunoidea: Arenaeus cribrarius, Callinectes danae, Callinectes ornatus, Callinectes sapidus, Achelous spinicarpus and Achelous spinimanus. A Multiple Response Permutation Procedure (MRPP) test indicated that the species composition differed significantly among the sampling sites, showing substantial heterogeneity in the composition and abundance of species among regions. The results suggest that C. danae was more abundant in waters with lower salinity and lower organic matter content. In contrast, A. spinimanus is positively correlated with these factors, showing a greater abundance under the opposite conditions. Callinectes ornatus appeared not to show strong selectivity for particular habitat characteristics. We conclude from these findings that areas affected by different phenomena produce changes in the composition and abundance of the assemblage of Portunoidea. Although the strength of eutrophication differs between UBA and MAC, the substantial continental inflow affecting SFS favors the development of species that complete their life cycle in the estuary.

Do oxidized zirconium femoral heads reduce polyethylene wear in cemented THAs? A blinded randomized clinical trial.

PubMed

Zaoui, Amine; Hage, Samer El; Langlois, Jean; Scemama, Caroline; Courpied, Jean Pierre; Hamadouche, Moussa

2015-12-01

Charnley low-friction torque total hip arthroplasty (THA) remains the gold standard in THA. The main cause for failure is wear of the socket. Highly crosslinked polyethylene (HXLPE) has been associated with reduced wear rates. Also, oxidized zirconium has shown in vitro reduced wear rates. However, to our knowledge, there are no data comparing oxidized zirconium femoral heads with metal heads against HXLPE or ultrahigh-molecular-weight polyethylene (UHMWPE) when 22.25-mm bearings were used, which was the same size that performed so well in Charnley-type THAs. We hypothesized that after a minimal 4-year followup (1) use of HXLPE would result in lower radiographic wear than UHMWPE when articulating with a stainless steel head or with an oxidized zirconium head; (2) use of oxidized zirconium would result in lower radiographic wear than stainless steel when articulating with UHMWPE and HXLPE; and (3) there would be no difference in terms of Merle d'Aubigné scores between the bearing couple combinations. One hundred patients were randomized to receive cemented THA with either oxidized zirconium or a stainless steel femoral head. UHMWPE was used in the first 50 patients, whereas HXLPE was used in the next 50 patients. There were 25 patients in each of the four bearing couple combinations. All other parameters were identical in both groups. Complete followup was available in 86 of these patients. Femoral head penetration was measured using a validated computer-assisted method dedicated to all-polyethylene sockets. Clinical results were compared between the groups using the Merle d'Aubigné score. In the UHMWPE series, the median steady-state penetration rate from 1 year onward was 0.03 mm/year (range, 0.003-0.25 mm/year) in the oxidized zirconium group versus 0.11 mm/year (range, 0.03-0.29 mm/year) in the metal group (difference of medians 0.08, p < 0.001). In the HXLPE series, the median steady-state penetration rate from 1 year onward was 0.02 mm/year (range, -0.32 to 0.07 mm/year) in the oxidized zirconium group versus 0.05 mm/year (range, -0.39 to 0.11 mm/year) in the metal group (difference of medians 0.03, p < 0.001). The Merle d'Aubigné scores were no different between the groups with a median of 18 in each of the groups (range, 16-18). This study demonstrated femoral head penetration was reduced by oxidized zirconium when compared with metal on both UHMWPE and HXLPE. However, apart the metal-UHMWE group, all other groups had a steady-state penetration rate well below the osteolysis threshold with a low difference between groups that might not be clinically important at this point. Longer-term followup is needed to warrant whether wear reduction will generate less occurrence of osteolysis and aseptic loosening. Level II, therapeutic study.

Pharmaceuticals in the environment: scientific evidence of risks and its regulation.

PubMed

Küster, Anette; Adler, Nicole

2014-11-19

During the past two decades scientists, regulatory agencies and the European Commission have acknowledged pharmaceuticals to be an emerging environmental problem. In parallel, a regulatory framework for environmental risk assessment (ERA) of pharmaceutical products has been developed. Since the regulatory guidelines came into force the German Federal Agency (UBA) has been evaluating ERAs for human and veterinary pharmaceutical products before they are marketed. The results show that approximately 10% of pharmaceutical products are of note regarding their potential environmental risk. For human medicinal products, hormones, antibiotics, analgesics, antidepressants and antineoplastics indicated an environmental risk. For veterinary products, hormones, antibiotics and parasiticides were most often discussed as being environmentally relevant. These results are in good correlation with the results within the open scientific literature of prioritization approaches for pharmaceuticals in the environment. UBA results revealed that prospective approaches, such as ERA of pharmaceuticals, play an important role in minimizing problems caused by pharmaceuticals in the environment. However, the regulatory ERA framework could be improved by (i) inclusion of the environment in the risk-benefit analysis for human pharmaceuticals, (ii) improvement of risk management options, (iii) generation of data on existing pharmaceuticals, and (iv) improving the availability of ERA data. In addition, more general and integrative steps of regulation, legislation and research have been developed and are presented in this article. In order to minimize the quantity of pharmaceuticals in the environment these should aim to (i) improve the existing legislation for pharmaceuticals, (ii) prioritize pharmaceuticals in the environment and (iii) improve the availability and collection of pharmaceutical data. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

[Testing the efficacy of disinfectants during drinking water treatment. A new experimental set-up at the German EPA (Umweltbundesamt - UBA)].

PubMed

Grützmacher, G; Bartel, H; Althoff, H W; Clemen, S

2007-03-01

A set-up for experiments in the flow-through mode was constructed in order to test the efficacy of substances used for disinfecting water during drinking water treatment. A flow-through mode - in contrast to experiments under stationary conditions (so-called batch experiments) - was chosen, because this experimental design allows experiments to be carried out under constant conditions for an extended time (up to one week) and because efficacy testing is possible repeatedly, simultaneously and under exactly the same conditions for short (about 0.5 min) and also longer (about 47 min) contact times. With this experimental design the effect of biofilms along the inner pipe surfaces can be included in the observations. The construction of the experimental set-up is based on experience with laboratory flow-through systems that were installed by the UBA's drinking water department (formerly Institute for Water-, Soil- and Air Hygiene (WaBoLu) Institute) for testing disinfection with chlorine. In the first step, a test pipe for the simulation of a water works situation was installed. Water of different qualities can be mixed in large volumes beforehand so that the experimental procedure can be run with constant water quality for a minimum of one week. The kinetics of the disinfection reaction can be observed by extracting samples from eight sampling ports situated along the test pipe. In order to assign exact residence times to each of the sampling ports, tracer experiments were performed prior to testing disinfectant efficacy. This paper gives the technical details of the experimental set-up and presents the results of the tracer experiments to provide an introduction with respect to its potential.

Graduate studies on optoelectronics in Argentina: an experience

NASA Astrophysics Data System (ADS)

Fernández, Juan C.; Garea, María. T.; Isaurralde, Silvia; Perez, Liliana I.; Raffo, Carlos A.

2014-07-01

The number of graduate programs in Optoelectronics in Argentina is scarce. The current Optics and Photonics Education Directory lists only three programs. One of them was launched in 2001 in the Facultad de Ingeniería (College of Engineering), Universidad de Buenos Aires (UBA). This was the first graduate program in the field, leading to a Master Degree in Optoelectronics. This decision arose from the demand of telecommunications industries and several estate- or private-funded research institutions working with us in the fields of lasers, optics, remote sensing, etc. A great bonus was the steady work, during several decades, of research groups in the College on the development of different type of lasers and optical non destructive tests and their engineering applications. As happened in many engineering graduate programs in Argentina at that time, few non full-time students could finish their studies, which called for 800 hours of traditional lecture-recitation classes, and the Master Thesis. In recent years Argentine Education authorities downsized the Master programs to 700 hours of blended learning and we redesigned the Graduate Optoelectronic Engineering Program to meet the challenge, dividing it in two successive one year programs, the first aimed at a professional training for almost immediate insertion in the labor market (called Especialización en Ingeniería Optoelectrónica), and the second (called Maestría en Ingeniería Optoelectrónica y Fotónica) aimed at a more academic and research target to comply with the UBA standards for Master degrees. The present work is a presentation of the new program design, which has begun in the current year.

Urinary bactericidal activity of single doses (250, 500, 750 and 1000 mg) of levofloxacin against fluoroquinolone-resistant strains of Escherichia coli.

PubMed

Stein, Gary E; Schooley, Sharon L; Nicolau, David P

2008-10-01

Increasing resistance to fluoroquinolones in uropathogens has become a clinical concern. The purpose of this study was to analyse the urinary bactericidal activity (UBA) of levofloxacin against fluoroquinolone-resistant strains of Escherichia coli. Ten healthy adult subjects (aged 23-60 years) received single doses of levofloxacin (250, 500, 750 and 1000 mg) and then blood and urine samples were collected in intervals (0-1.5, 1.5-4, 4-8, 8-12 and 12-24h) over 24h. Both serum and urine concentrations were measured by a validated high-performance liquid chromatography assay. Bactericidal titres in urine were determined against E. coli isolates with minimum inhibitory concentrations of 0.125, 4, 8, 16, 32 and 64microg/mL for levofloxacin. The mean serum pharmacokinetic parameters for these doses of levofloxacin were similar to previously published values. The mean peak urinary concentrations (0-1.5h) were 210, 347, 620 and 536microg/mL for the 250, 500, 750 and 1000 mg dose, respectively. Each dose of levofloxacin exhibited early (0-1.5h time period) bactericidal activity in urine in virtually all subjects against E. coli strains with MICs

Ufmylation and FATylation Pathways are Down Regulated in Human Alcoholic and Non Alcoholic Steatohepatitis, and Mice Fed DDC, where Mallory-Denk Bodies (MDBs) Form

PubMed Central

Liu, H; Li, J; Tillman, B; French, BA; French, SW

2014-01-01

We previously reported the mechanisms involved in the formation of Mallory-Denk bodies (MDBs) in mice fed DDC. To further provide clinical evidence as to how ubiquitin-like protein (Ubls) modification, gene transcript expression in Ufmylation and FATylation were investigated in human archived formalin-fixed, paraffin-embedded (FFPE) liver biopsies and frozen liver sections from DDC re-fed mice were used. Real-time PCR analysis showed that all Ufmylation molecules (Ufm1, Uba5, Ufc1, Ufl1 and UfSPs) were significantly down regulated, both in DDC re-fed mice livers and patients’ livers where MDBs had formed, indicating that gene transcript changes were limited to MDB-forming livers where the protein quality control system was down regulated. FAT10 and subunits of the immunoproteasome (LMP2 and LMP7) were both up regulated as previously shown. An approximate 176- and 5-fold up regulation (respectively) of FAT10 were observed in the DDC re-fed mice liver and in the livers of human alcoholic hepatitis with MDBs present, implying that there was an important role played by this gene. The FAT10-specific E1 and E2 enzymes Uba6 and USE1, however, were found to be down regulated both in patients’ livers and in the liver of DDC re-fed mice. Interestedly, the down regulation of mRNA levels was proportionate to MDB abundance in the liver tissues. Our results show the first systematic demonstration of transcript regulation of Ufmylation and FATylation in the liver of patients who form MDBs, where protein quality control is down regulated. This was also shown in livers of DDC re-fed mice where MDBs had formed. PMID:24893112

Ufmylation and FATylation pathways are downregulated in human alcoholic and nonalcoholic steatohepatitis, and mice fed DDC, where Mallory-Denk bodies (MDBs) form.

PubMed

Liu, H; Li, J; Tillman, B; French, B A; French, S W

2014-08-01

We previously reported the mechanisms involved in the formation of Mallory-Denk bodies (MDBs) in mice fed DDC. To further provide clinical evidence as to how ubiquitin-like protein (Ubls) modification, gene transcript expression in Ufmylation and FATylation were investigated in human archived formalin-fixed, paraffin-embedded (FFPE) liver biopsies and frozen liver sections from DDC re-fed mice were used. Real-time PCR analysis showed that all Ufmylation molecules (Ufm1, Uba5, Ufc1, Ufl1 and UfSPs) were significantly downregulated, both in DDC re-fed mice livers and patients' livers where MDBs had formed, indicating that gene transcript changes were limited to MDB-forming livers where the protein quality control system was downregulated. FAT10 and subunits of the immunoproteasome (LMP2 and LMP7) were both upregulated as previously shown. An approximate 176- and 5-fold upregulation (respectively) of FAT10 was observed in the DDC re-fed mice liver and in the livers of human alcoholic hepatitis with MDBs present, implying that there was an important role played by this gene. The FAT10-specific E1 and E2 enzymes Uba6 and USE1, however, were found to be downregulated both in patients' livers and in the liver of DDC re-fed mice. Interestedly, the downregulation of mRNA levels was proportionate to MDB abundance in the liver tissues. Our results show the first systematic demonstration of transcript regulation of Ufmylation and FATylation in the liver of patients who form MDBs, where protein quality control is downregulated. This was also shown in the livers of DDC re-fed mice where MDBs had formed. Copyright © 2014 Elsevier Inc. All rights reserved.

Biallelic UFM1 and UFC1 mutations expand the essential role of ufmylation in brain development.

PubMed

Nahorski, Michael S; Maddirevula, Sateesh; Ishimura, Ryosuke; Alsahli, Saud; Brady, Angela F; Begemann, Anaïs; Mizushima, Tsunehiro; Guzmán-Vega, Francisco J; Obata, Miki; Ichimura, Yoshinobu; Alsaif, Hessa S; Anazi, Shams; Ibrahim, Niema; Abdulwahab, Firdous; Hashem, Mais; Monies, Dorota; Abouelhoda, Mohamed; Meyer, Brian F; Alfadhel, Majid; Eyaid, Wafa; Zweier, Markus; Steindl, Katharina; Rauch, Anita; Arold, Stefan T; Woods, C Geoffrey; Komatsu, Masaaki; Alkuraya, Fowzan S

2018-06-02

The post-translational modification of proteins through the addition of UFM1, also known as ufmylation, plays a critical developmental role as revealed by studies in animal models. The recent finding that biallelic mutations in UBA5 (the E1-like enzyme for ufmylation) cause severe early-onset encephalopathy with progressive microcephaly implicates ufmylation in human brain development. More recently, a homozygous UFM1 variant was proposed as a candidate aetiology of severe early-onset encephalopathy with progressive microcephaly. Here, we establish a locus for severe early-onset encephalopathy with progressive microcephaly based on two families, and map the phenotype to a novel homozygous UFM1 mutation. This mutation has a significantly diminished capacity to form thioester intermediates with UBA5 and with UFC1 (the E2-like enzyme for ufmylation), with resulting impaired ufmylation of cellular proteins. Remarkably, in four additional families where eight children have severe early-onset encephalopathy with progressive microcephaly, we identified two biallelic UFC1 mutations, which impair UFM1-UFC1 intermediate formation with resulting widespread reduction of cellular ufmylation, a pattern similar to that observed with UFM1 mutation. The striking resemblance between UFM1- and UFC1-related clinical phenotype and biochemical derangements strongly argues for an essential role for ufmylation in human brain development. The hypomorphic nature of UFM1 and UFC1 mutations and the conspicuous depletion of biallelic null mutations in the components of this pathway in human genome databases suggest that it is necessary for embryonic survival, which is consistent with the embryonic lethal nature of knockout models for the orthologous genes.

E54-1403

NASA Image and Video Library

1954-09-17

B-47A Stratojet on ramp with pilots and crew. In 1954 after a research flight in the Boeing B-47A Stratojet Crew Chief Wilbur McClenaghan (center) asks of the pilots if there are any "squawks" that should be taken care of before the next flight. Pilots are Joe Walker on the viewer's left and Stanley Butchart on the right. Data system technician Merle Curtis, in coveralls, is busy checking the airdata head mounted on the nose boom with the help of Instrumentation Crew Chief Raymond Langley. The door to the cockpit area is open showing a view of the ladder that folds down to be used by the pilots to enter and leave the area.

Luxation traumatique invétérée de la hanche

PubMed Central

Rachid, Abdelillah; Abdeljaouad, Najib; Abdelkrim, Daoudi; Hicham, Yacoubi

2015-01-01

La luxation traumatique invétérée de la hanche est une affection rare et grave avec une prise en charge difficile et non encore codifiée. L'arthroplastie totale de la hanche reste le traitement chirurgical de choix. Nous rapportons un cas de luxation iliaque invétérée de la hanche chez un jeune patient de 19 ans, traitée par une arthroplastie totale de la hanche. Après un recul de 2 ans, le résultat fonctionnel est satisfaisant, avec une marche indolore sans aide. Le Score de Harris est de 96 et le score de Merle d'aubigné-Postel est de 17. PMID:26848347

Global, decaying solutions of a focusing energy-critical heat equation in R4

NASA Astrophysics Data System (ADS)

Gustafson, Stephen; Roxanas, Dimitrios

2018-05-01

We study solutions of the focusing energy-critical nonlinear heat equation ut = Δu - | u|2 u in R4. We show that solutions emanating from initial data with energy and H˙1-norm below those of the stationary solution W are global and decay to zero, via the "concentration-compactness plus rigidity" strategy of Kenig-Merle [33,34]. First, global such solutions are shown to dissipate to zero, using a refinement of the small data theory and the L2-dissipation relation. Finite-time blow-up is then ruled out using the backwards-uniqueness of Escauriaza-Seregin-Sverak [17,18] in an argument similar to that of Kenig-Koch [32] for the Navier-Stokes equations.

Geothermal greenhouse-heating facilities for the Klamath County Nursing Home, Klamath Falls, Oregon

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

Not Available

The Klamath County Nursing Home, located in Klamath Falls, Oregon, was constructed in 1976. The building of 55,654 square feet currently houses care facilities for approximately 120 persons. During the initial planning for the Nursing Home, the present site was selected primarily on the basis of its geothermal resource. This resource (approx. 190/sup 0/F) currently provides space and domestic hot water heating for the Nursing Home, Merle West Medical Center and the Oregon Institute of Technology. The feasibility of installing a geothermal heating system in a planned greenhouse for the Nursing Home is explored. The greenhouse system would be tiedmore » directly to the existing hot water heating system for the Nursing Home.« less

Toxicological and ecotoxicological assessment of water tracers

NASA Astrophysics Data System (ADS)

Behrens, H.; Beims, U.; Dieter, H.; Dietze, G.; Eikmann, T.; Grummt, T.; Hanisch, H.; Henseling, H.; Käß, W.; Kerndorff, H.; Leibundgut, C.; Müller-Wegener, U.; Rönnefahrt, I.; Scharenberg, B.; Schleyer, R.; Schloz, W.; Tilkes, F.

2001-06-01

Uncertainties regarding possible negative effects on the environment or on human health of authorizing tracing experiments in groundwater and surface waters led to the establishment of a Working Group at the German Federal Environmental Agency (Umweltbundesamt - UBA) for conducting a toxicological and ecotoxicological assessment. A total of 17 water tracers was assessed by the Working Group on the basis of the results of toxicological tests, the available literature, and the group's expert knowledge. In the future, tracers that pose a risk to the environment or to human health should no longer be used. Nevertheless, there are a number of tracers that could be used in hydrogeological and hydrological investigations for water-pollution-control purposes with no adverse environmental impact.

Prevalence of molar-incisor hypomineralization (MIH) in children seeking dental care at the Schools of Dentistry of the University of Buenos Aires (Argentina) and University of la Republica (Uruguay).

PubMed

Biondi, Ana M; López Jordi, María del C; Cortese, Silvina G; Alvarez, Licet; Salveraglio, Inés; Ortolani, Andrea M

2012-01-01

The objectives of this study are to compare the prevalence of MIH in children seeking dental care spontaneously at the Department of Comprehensive Children's Dentistry of the University of Buenos Aires (UBA) and Department of Pediatric Dentistry of the University of La República (UdelaR) and to analyze the distribution according to year of birth, sex, age, number of affected teeth and maximum degree of severity in molars and incisors. During 2010, nine pediatric dentists from both schools (Kappa = 0.94) assessed all children born between 1993 and 2003 whose 4 first molars and 8 permanent incisors had erupted. Specially designed charts were used to record sex, year of birth, institution, presence of MIH, number of affected incisors and molars and maximum degree of severity for each tooth. Two groups were formed: UBA: A (n = 512) and UdelaR: B (n = 463). 975 children (11.6 +/- 2.67 years) were evaluated. The prevalence of MIH in the total sample was 6.56%, without significant differences between A and B (p = 0.76). There was no significant difference between groups regarding age (p = 0. 95) or sex (p = 0.30). A significant increase was found in both institutions according to year of birth during the study period. (A: p = 0.0017) B: p = 0. 0058). The results of this study show a similar prevalence of MIH among patients seeking dental care at the Schools of Dentistry of the University of Buenos Aires (Argentina) and University of la República (Uruguay). No significant difference was found comparing the distribution by sex, affected teeth or severity of each tooth. A highly significant positive correlation was found regarding the year of birth. The relevance of MIH as an emerging pathology requires studies on larger samples covering the entire countries.

[Ambroise Paré in French literature].

PubMed

Dumaitre, P

1995-01-01

The 16th century by its passionate side has been the favourite one of authors of historical novels in which among the heroes of "cloak and dagger stories" appears sometime Ambroise Paré. Alexandre Dumas (the father) has shown him at the court of Charles IX in La Reine Margot (1845) where he does not however play a great role. On the contrary, Balzac in Le Martyr calviniste (1842) has given him a capital part close to the dying François II, whom he intended to trepanize but had to give up this idea as a consequence of the opposition of the queen-mother Catherine de Médicis. In the present century, Robert Merle in Paris ma bonne ville (Fortune de France, 3, 1980) shows Paré at the time of the Saint Barthélemy.

[A new mechanism of ubiquitin-dependent proteolytic pathway--polyubiquitin chain recognition and proteasomal targeting].

PubMed

Kawahara, Hiroyuki; Yokosawa, Hideyoshi

2008-01-01

The RPN10 subunit of 26S proteasome and several UBA domain proteins can bind to the polyubiquitin chain and play a role as ubiquitin receptors of the 26S proteasome. Although it was thought that substrate recognition is an essential step in the proteasome-mediated protein degradation, deletion of rpn10 genes in yeast does not influence the viability of cells but instead causes only a mild phenotype, suggesting that the above ubiquitin receptors are redundantly involved in substrate delivery to the proteasome. However, their functional difference is still enigmatic. In this review, we summarize recent advances in polyubiquitin chain recognition/delivery system and provide potential applications to modulate this system as a probable target for drug development.

Environmental magnetism and effective radium concentration: the case study of the painted cave of Pech Merle, France

NASA Astrophysics Data System (ADS)

Isambert, Aude; Girault, Frédéric; Perrier, Frédéric; Bouquerel, Hélène; Bourges, François

2017-04-01

Painted caves, showing testimony of prehistoric art, are nowadays subject to intense attention to understand the conditions of stability and avoid degradation. The preservation of cultural sequences and archaeological artefacts represents especially a crucial issue in the case of caves opened to visitors. For this purpose, a better knowledge of these preserved environments that imprint paleoenvironmental conditions at the time of deposition is needed. In this context, different environmental parameters of the Pech Merle cave, in France, are currently actively monitored including temperature, hygrometry, and gas measurements such as CO2 and radon-222 (decay product of radium-226). This temporal monitoring needs to be complemented by a detailed characterisation of the site, including petrophysical and mineralogical properties. To better constrain the environmental and paleoenvironmental context, more than 100 samples including soils, sediments, rocks and speleothems were collected inside and outside the cave area. We report here magnetic properties of powdered samples (low-field susceptibility, hysteresis parameters, and saturation magnetization) coupled with effective radium concentration (ECRa) measurements. We observe that magnetic susceptibility, which ranges over 5 orders of magnitude from calcareous rocks to topsoils and argillaceous filling deposits, correlates well with ECRa values. This correlation, previously observed (Girault et al., 2016) in very different geological contexts, could be interpreted as a common concentration of sources, also indicating a signature of natural samples to the contrary of anthropic environments disturbed by human activities, in which case the association is blurred. This study demonstrates the general interest of combining two different parameters - here low-field magnetic susceptibility and effective radium concentration determined using non-destructive techniques in the field and in the laboratory - to physically characterize geosystems and to propose a novel approach to discriminate naturally preserved and human-impacted or polluted sites. Girault, F., Perrier, F., Poitou, C., Isambert, A., Théveniaut, H., Laperche, V., ... & Douay, F. (2016). Effective radium concentration in topsoils contaminated by lead and zinc smelters. Science of The Total Environment, 566, 865-876.

The Anterior Intrapelvic Approach for Acetabular Fractures Using Approach-Specific Instruments and an Anatomical-Preshaped 3-Dimensional Suprapectineal Plate.

PubMed

Gras, Florian; Marintschev, Ivan; Grossterlinden, Lars; Rossmann, Markus; Graul, Isabel; Hofmann, Gunther O; Rueger, Johannes M; Lehmann, Wolfgang

2017-07-01

Anatomical acetabular plates the anterior intrapelvic approach (AIP) were recently introduced to fix acetabular fractures through the intrapelvic approach. Therefore, we asked the following: (1) Does the preshaped 3-dimensional suprapectineal plate interfere with or even impair the fracture reduction quality? (2) How often does the AIP approach need to be extended by the first (lateral) window of the ilioinguinal approach? Observational case series. Two Level 1 trauma centers. Patients with unstable acetabular fractures in 2014. Fracture fixation with anatomical-preshaped, 3-dimensional suprapectineal plates through the AIP approach ± the first window of the ilioinguinal approach. Fracture reduction results were measured in computed tomography scans and graded according to the Matta quality of reduction. Intraoperative parameters and perioperative complications were recorded. Radiological results (according to Matta) and functional outcome (modified Merle d'Aubigné score) were evaluated at 1-year follow-up. Thirty patients (9 women + 21 men; mean age ± SE: 64 ± 8 years) were included. The intrapelvic approach was solely used in 19 cases, and in 11 cases, an additional extension with the first window of the ilioinguinal approach (preferential for 2-column fractures) was performed. The mean operating time was 202 ± 59 minutes; the fluoroscopic time was 66 ± 48 seconds. Fracture gaps and steps in preoperative versus postoperative computed tomography scans were 12.4 ± 9.8 versus 2.0 ± 1.5 and 6.0 ± 5.5 versus 1.3 ± 1.7 mm, respectively. At 13.4 ± 2.9 months follow-up, the Matta grading was excellent in 50%, good in 25%, fair in 11%, and poor in 14% of cases. The modified Merle d'Aubigné score was excellent in 17%, good in 37%, fair in 33%, and poor in 13% of cases. The AIP approach using approach-specific instruments and an anatomical-preshaped, 3-dimensional suprapectineal plate became the standard procedure in our departments. Radiological and functional early results justify joint preserving surgery in most cases. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Outcomes using wedge stem with full hydroxiapatite coverage with a minimum of 5 years' follow-up.

PubMed

Godoy-Monzon, D; Buttaro, M; Comba, F; Zanotti, G; Piccaluga, F; Neira-Borrajo, I

Total Hip Arthroplsty (THA) using uncemented stems is a popular practice in the last decades. The implant survivorship is crtitical and a less than 10% revision at 10 years is been propesed for commercialization and use. To analyse the clinicoradiological results of an uncemented hydroxiapatite covered wedge stem with a 5 years minimum follow up. Prospective study, patients aged from 21-75years were included. All patients received an Element stem (Exactech) and uncemented cup with crosslink poly and 32 mm metal head, and posterior approach with piriformis retention was used. Scheduled clinical and radiographic evaluation at 3 weeks, 3-6 month, year and subsequent years using Harris Hip Score and Merle d'Aubigné Postel. Intraoperative and during follow up complications were recorded. One hundred and fourteen total hip replacements in 104 patients: 54 females and 50 males (52%/48%). Follow-up of 5.7 years (range, 5-6.2years). Average age 56.8years (range, 42-75years). Clinical evaluation the Merle d'Aubigné score improved 6.8 points and from the initianl Harris Hip Score 47.3 to 93.1 points at last follow up. Radiographic evaluation shows osteointegration in all stems. And in 6 cases (5.3% at 3 months subsidence was detected, average 1.4 mm (range 0-2.6 mm) with no clinical manifestation, 3 cases of subsidence were associated to intraoperative fractures (1 greater trochanter and 2 in the calcar area, all resolved with wire cerclaje). Subjective evaluation: 86 cases (82.6%) excellent, 9 patients (8.6%) good, 6 cases (5.9%) satisfactory and 3 cases (2.9%) poor. All poor results linked to the intraoperative complications. No patient lost during follow up period. No femoral pain dislocation or aseptic or loosening detected. All implants were in situ at last follow up. The radiological results confirm the benefits of this type of stem with good osteointegration. The clinical and subjective results are promising. With good surgical technical and without complications the risk of aseptic loosening should be absent or minimal. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Greenhouse gas emissions from municipal wastewater treatment plants

NASA Astrophysics Data System (ADS)

Parravicini, Vanessa; Svardal, Karl

2016-04-01

Operating wastewater treatment plants (WWTP) represent a source of greenhouse gases (GHG). Direct GHG emissions include emissions of methane (CH4) and nitrous oxide (N2O) that can be biologically produced during wastewater and sewage sludge treatment. This is also highlighted in the Intergovernmental Panel on Climate Change (IPCC 2006) guidelines used for national GHG inventories. Indirect GHG emissions occur at WWTPs mainly by the consumption of electricity, fossil fuel for transportation and by the use of chemicals (e.g. coagulants). In this study, the impact of direct and indirect GHG emissions was quantified for two model WWTPs of 50.000 person equivalents (p.e.) using carbon footprint analyses. It was assumed that at one WWTP sewage sludge is digested anaerobically, at the other one it is aerobically stabilised in the activated sludge tank. The carbon footprint analyses were performed using literature emission factors. A new estimation model based on measurements at eight Austrian WWTPs was used for the assessment of N2O direct emissions (Parravicini et al., 2015). The results of the calculations show that, under the selected assumptions, the direct N2O emission from the activated sludge tank can dominate the carbon footprint of WWTP with a poor nitrogen removal efficiency. Through an improved operation of nitrogen removal several advantages can be gained: direct N2O emissions can be reduced, the energy demand for aeration can be decreased and a higher effluent quality can be achieved. Anaerobic digesters and anaerobic sludge storage tanks can become a relevant source of direct CH4 emissions. Minimising of CH4 losses from these sources improves the carbon footprint of the WWTP also increasing the energy yield achievable by combusting this renewable energy carrier in a combined heat and power unit. The estimated carbon footprint of the model WWTPs lies between 20 and 40 kg CO2e/p.e./a. This corresponds to 0.2 to 0.4% of the CO2e average emission caused yearly by a person in Germany or Austria (10.6 t CO2e/p/a, UBA, 2016). The results indicate that GHG emissions from WWTP have at global scale a small impact, as also highlighted by the Austrian national inventory report (NIR, 2015), where the estimated CO2e emissions from WWTPs account for only 0.23% of the total CO2e emission in Austria. References IPCC (2006). Intergovernmental Panel on Climate Change, Guidelines for National Greenhouse Gas Inventories, Prepared by the National Greenhouse Gas Inventories Program, Eggleston H.S., Buendia L., Miwa K., Ngara T. and Anabe K. (eds). Published: IGES, Japan. http://www.ipcc-nggip.iges.or.jp/public/2006gl/. NIR (2015). Austria's National Inventory Report 2015. Submission under the United Nations Framework Convention on Climate Change and under the Kyoto Protocol. Reports, Band 0552, ISBN: 978-3-99004-364-6, Umweltbundesamt, Wien. Parravicini V., Valkova T., Haslinger J., Saracevic E., Winkelbauer A., Tauber J., Svardal K., Hohenblum P., Clara M., Windhofer G., Pazdernik K., Lampert C. (2015). Reduktionspotential bei den Lachgasemissionen aus Kläranlagen durch Optimierung des Betriebes (ReLaKO). The research project was financially supported by the Ministry for agriculture, forestry, Environment and Water Management. Project leader: TU Wien, Institute for Water Quality, Ressources and Waste Management; Project partner: Umweltbundesamt GmbH. Final report: http://www.bmlfuw.gv.at/service/publikationen/wasser/Lachgasemissionen---Kl-ranlagen.html. UBA (2016). German average carbon footprint. Umweltbundesamt, Januar 2016, http://uba.klimaktiv-co2-rechner.de/de_DE/page/footprint/

The relevance of "non-relevant metabolites" from plant protection products (PPPs) for drinking water: the German view.

PubMed

Dieter, Hermann H

2010-03-01

"Non-relevant metabolites" are those degradation products of plant protection products (PPPs), which are devoid of the targeted toxicities of the PPP and devoid of genotoxicity. Most often, "non-relevant metabolites" have a high affinity to the aquatic environment, are very mobile within this environment, and, usually, are also persistent. Therefore, from the point of drinking water hygiene, they must be characterized as "relevant for drinking water" like many other hydrophilic/polar environmental contaminants of different origins. "Non-relevant metabolites" may therefore penetrate to water sources used for abstraction of drinking water and may thus ultimately be present in drinking water. The presence of "non-relevant metabolites" and similar trace compounds in the water cycle may endanger drinking water quality on a long-term scale. During oxidative drinking water treatment, "non-relevant metabolites" may also serve as the starting material for toxicologically relevant transformation products similar to processes observed by drinking water disinfection with chlorine. This hypothesis was recently confirmed by the detection of the formation of N-nitroso-dimethylamine from ozone and dimethylsulfamide, a "non-relevant metabolite" of the fungicide tolylfluanide. In order to keep drinking water preferably free of "non-relevant metabolites", the German drinking water advisory board of the Federal Ministry of Health supports limiting their penetration into raw and drinking water to the functionally (agriculturally) unavoidable extent. On this background, the German Federal Environment Agency (UBA) recently has recommended two health related indication values (HRIV) to assess "non-relevant metabolites" from the view of drinking water hygiene. Considering the sometimes incomplete toxicological data base for some "non-relevant metabolites", HRIV also have the role of health related precautionary values. Depending on the completeness and quality of the toxicological evaluation of a "non-relevant metabolite", its HRIV is either set as 1.0 microg/l (HRIV(a)) or as 3.0 microg/l (HRIV(b)) for lifelong exposure. In case a HRIV would be exceeded, UBA recommends to keep on a precautionary action value (PAV) of 10 microg/l for each "non-relevant metabolite". The HRIV(b) is similar to the maximal value derived by application of the TTC-concept for Cramer Class III (4.5 microg/l). The HRIV(a) and the PAV are similar to values in the EU-guidance document for assessing "non-relevant metabolites" in ground water, with the important difference that the drinking water PAV is not intended to be tolerated for permanent exposure. Drinking water containing "non-relevant metabolites" below the respective HRIVs can also be considered as being sufficiently protective against toxicologically relevant oxidative transformation products which may be formed from "non-relevant metabolites" during drinking water treatment with ozone. However, even drinking water where one or several "non-relevant metabolites" are detected above substance-specific HRIVs is suited for human consumption without health risks. Only in special cases (relatively high "non-relevant metabolite" - concentrations), it could be indicated to examine the finished water for transformation products after treatment with ozone if there are no further treatment steps to eliminate or degrade polar compounds. UBA's "non-relevant metabolite-Recommendation" from April 2008 was positively picked up in 2009 by four important stakeholders in the domain of drinking water management as part of a voluntary cooperation agreement. The aim of such cooperation is to limit the transport of "non-relevant metabolites" into the drinking water to the functionally (and agriculturally) unavoidable extent and insofar to meet special precautionary demands. (c) 2009 Elsevier Inc. All rights reserved.

Cup-cage construct for acute fractures of the acetabulum, re-defining indications.

PubMed

Chana-Rodríguez, Francisco; Villanueva-Martínez, Manuel; Rojo-Manaute, Jose; Sanz-Ruíz, Pablo; Vaquero-Martín, Javier

2012-12-01

Acetabular fractures in the elderly are challenging injuries. The use of a trabecular metal acetabular cage was investigated as the treatment option in a series of elderly patients with acetabular fractures. At a 2-year follow up, 6 elderly patients were found to have mimimum pain, increased function, and increased scores using the Merle d'Aubigné and Postel system modified by Charnley. Radiographically, the areas of morsellised autograft that surrounded the cups were seen to have incorporated uniformly well, and the acetabular fractures were healed within six months after surgery. No mechanical failure, screw breakage, loosening, or migration was noticed. This novel indication of the cup-cage construction that uses revision techniques, for selected patients and fractures, to achieve an acute stable reconstruction, should be considered as an alternative reconstruction option in elderly patients presenting with acetabular fractures. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical and Thermal Analysis

NASA Technical Reports Server (NTRS)

Bulluck, J. W.; Rushing, R. A.

1995-01-01

During the past six months we have conducted significant research in several domains in order to clarify and understanding the aging and chemical failure mechanism of thermoplastics (PVDF or Tefzel) for pipes. We organized numerous analytical studies with methods including Fourier Transform Infrared Spectroscopy, Dynamic Mechanical Analysis, Differential Scanning Calorimetry, and Stress Relaxation experiments. In addition we have reanalyzed previous thermogravimetric data concerning the rate of deplasticization of Coflon pipe. We investigated a number of aged samples of both Tefzel and Coflon that were forwarded from MERL. We conducted stress relaxation experiments of Coflon pipe at several temperatures and determined an activation energy. We also examined the dynamic mechanical response PVDF during deplasticization and during methanol plasticization. We performed numerous DSC analyses to research the changing crystalline morphology. We have noted significant changes in crystallinity upon aging for both PVDF and Tefzel. Little variation in elemental composition was noted for many of the aged Coflon and Tefzel samples tested.

Constraints and changes in the development of science and technology policies in Argentina's University of Buenos Aires and the National Autonomous University of Mexico

NASA Astrophysics Data System (ADS)

Alcantara, Armando

1999-06-01

This dissertation is a comparison of the effects of structural adjustment on scientific and technological policies in two of the largest and most important universities of Latin America, UBA and UNAM. In its broadest sense, scientific and technological policies encompass a set of interventions, decisions, and activities of different institutions within a given society aimed to hinder or stimulate the progress of scientific research, and the application of its products to socioeconomic, political, cultural or military objectives. The methodological approach for this dissertation aimed to combine data collected at both the macro and micro levels. First, a profound examination of different bibliographical sources such as books, articles, and documents of different kinds (policy papers, national plans, and working papers), was carried out. Secondly, a series of interviews were conducted with scientists in some of the natural sciences' research centers and institutes, academic administrators and top officials of the S&T government agencies, in Argentina and Mexico, The main goal of these interviews was to understand the institutional dynamics as it was shaped by actors and processes, outside and within the two universities. This study found that the structural adjustment process in Argentina and Mexico has negatively affected the S&T policies in both UBA and UNAM. Local S&T played a original role in the two universities under scrutiny. Investments in science and technology have remained significantly low in Argentina and Mexico. In addition to this, the small amount of scientific personnel, the predominantly public characteristic of S&T funds, and the reduced number of doctoral graduates resulted in low levels of scientific output as compared with the number of publications in international scientific literature. A predominant academic orientation with few contributions to societal needs, either related to the productive sectors or to social problems such as pollution, energy, food, and health, among others, was also seen. A coherent and articulated S&T policy linking the university, the state, and the productive sectors, could only be achieved if it is included in a different economic strategy that would go beyond the limitations of the neoliberal model.

Time Burden of Standardized Hip Questionnaires.

PubMed

Chughtai, Morad; Khlopas, Anton; Mistry, Jaydev B; Gwam, Chukwuweike U; Elmallah, Randa K; Mont, Michael A

2016-04-01

Many standardized scales and questionnaires have been developed to assess outcomes of patients undergoing total hip arthroplasty (THA). However, these surveys can be a burden to both patients and orthopaedists as some are time-inefficient. In addition, there is a paucity of reports assessing the time it takes to complete them. In this study we aimed to: (1) assess how long it takes to complete the most common standardized hip questionnaires; (2) determine the presence of variation in completion time; and (3) evaluate the effects of age, gender, and level of education on completion time. Based on a previous study, we selected the seven most commonly used hip scoring systems-Western Ontario and McMaster Universities Hip Outcome Assessment (WOMAC), Harris Hip Score (HHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), Larson Score, Short-form 36 (SF-36), modified Merle d'Aubigne and Postel Score (MDA), and Lower Extremity Functional Scale (LEFS). The standardized scales and questionnaires were randomly administered to 70 subjects. The subjects were unaware that they were being timed during completion of the questionnaire. We obtained the coefficients of variation of time for each questionnaire. The mean time to complete the questionnaire was then stratified and compared based on age, gender, and level of education. The mean time to complete each of the systems is listed in ascending order: Modified Merle d'Aubigne and Postel Score (MDA), Lower Extremity Functional Scale (LEFS), Western Ontario and McMaster Universities Hip Outcome Assessment (WOMAC), Harris Hip Score (HHS), Larson Score, Hip Disability and Osteoarthritis Outcome Score (HOOS), and Short-form 36 (SF-36). The WOMAC and Larson Score coefficients of variation were the largest, and the HOOS and MDA were the smallest. There was a significantly higher mean time to completion in those who were above or equal to the age of 55 years as compared to those who were below the age of 55 (227 vs. 166 seconds). There was no significant association found in time of completion between gender or education level. Standardized scales and questionnaire which assess THA patients can be burdensome and time-inefficient, which may lead to task-induced fatigue. This may result in inaccurate THA patient assessments, which do not reflect the patient's true state. Future studies should aim to create an encompassing questionnaire that is time efficient and can replace all currently used validated systems.

Proteasome subunit Rpn13 is a novel ubiquitin receptor

PubMed Central

Husnjak, Koraljka; Elsasser, Suzanne; Zhang, Naixia; Chen, Xiang; Randles, Leah; Shi, Yuan; Hofmann, Kay; Walters, Kylie; Finley, Daniel; Dikic, Ivan

2010-01-01

Proteasomal receptors that recognize ubiquitin chains attached to substrates are key mediators of selective protein degradation in eukaryotes. Here we report the identification of a new ubiquitin receptor, Rpn13/ARM1, a known component of the proteasome. Rpn13 binds ubiquitin via a conserved N-terminal region termed the Pru domain (Pleckstrin-like receptor for ubiquitin), which binds K48-linked diubiquitin with an affinity of ∼90 nM. Like proteasomal ubiquitin receptor Rpn10/S5a, Rpn13 also binds ubiquitin-like domains of the UBL/UBA family of ubiquitin receptors. A synthetic phenotype results in yeast when specific mutations of the ubiquitin binding sites of Rpn10 and Rpn13 are combined, indicating functional linkage between these ubiquitin receptors. Since Rpn13 is also the proteasomal receptor for Uch37, a deubiquitinating enzyme, our findings suggest a coupling of chain recognition and disassembly at the proteasome. PMID:18497817

The cell cycle of early mammalian embryos: lessons from genetic mouse models.

PubMed

Artus, Jérôme; Babinet, Charles; Cohen-Tannoudji, Michel

2006-03-01

Genes coding for cell cycle components predicted to be essential for its regulation have been shown to be dispensable in mice, at the whole organism level. Such studies have highlighted the extraordinary plasticity of the embryonic cell cycle and suggest that many aspects of in vivo cell cycle regulation remain to be discovered. Here, we discuss the particularities of the mouse early embryonic cell cycle and review the mutations that result in cell cycle defects during mouse early embryogenesis, including deficiencies for genes of the cyclin family (cyclin A2 and B1), genes involved in cell cycle checkpoints (Mad2, Bub3, Chk1, Atr), genes involved in ubiquitin and ubiquitin-like pathways (Uba3, Ubc9, Cul1, Cul3, Apc2, Apc10, Csn2) as well as genes the function of which had not been previously ascribed to cell cycle regulation (Cdc2P1, E4F and Omcg1).

Detection of spectroscopic binaries: lessons from the Gaia-ESO survey

NASA Astrophysics Data System (ADS)

van der Swaelmen, Mathieu; Merle, Thibault; van Eck, Sophie; Jorissen, Alain; Zwitter, Tomaž

2018-04-01

The Gaia-ESO survey (GES; Gilmore et al. (2012), Randich et al. (2013)) is a spectroscopic survey complementing the Gaia mission to bring accurate radial velocities and chemical abundances for 105 stars. Merle et al. (submitted to A&A see also this volume) developped a tool (DOE) to detect multiple peaks in the cross-correlation functions (CCFs) of GES spectra. Using the GIRAFFE HR10 and HR21 settings, we were able to compare the efficiency of our SB detection tool depending on the wavelength range and resolution. We show that a careful design of CCF masks can improve the detection rate in the HR21 settings. HR21 spectra are similar to the ones produced by the RVS spectrograph of the Gaia mission, though the lower resolution of RVS spectra may result in a lower detection efficiency than the case of HR21. Analysis of RVS spectra in the context of spectroscopic binaries can take advantage of the lessons learnt from the GES to maximize the detection rate.

SVBRDF-Invariant Shape and Reflectance Estimation from a Light-Field Camera.

PubMed

Wang, Ting-Chun; Chandraker, Manmohan; Efros, Alexei A; Ramamoorthi, Ravi

2018-03-01

Light-field cameras have recently emerged as a powerful tool for one-shot passive 3D shape capture. However, obtaining the shape of glossy objects like metals or plastics remains challenging, since standard Lambertian cues like photo-consistency cannot be easily applied. In this paper, we derive a spatially-varying (SV)BRDF-invariant theory for recovering 3D shape and reflectance from light-field cameras. Our key theoretical insight is a novel analysis of diffuse plus single-lobe SVBRDFs under a light-field setup. We show that, although direct shape recovery is not possible, an equation relating depths and normals can still be derived. Using this equation, we then propose using a polynomial (quadratic) shape prior to resolve the shape ambiguity. Once shape is estimated, we also recover the reflectance. We present extensive synthetic data on the entire MERL BRDF dataset, as well as a number of real examples to validate the theory, where we simultaneously recover shape and BRDFs from a single image taken with a Lytro Illum camera.

Effectiveness of interventions to reduce exposure to lead through consumer products and drinking water: A systematic review.

PubMed

Pfadenhauer, Lisa Maria; Burns, Jacob; Rohwer, Anke; Rehfuess, Eva Annette

2016-05-01

The objective of this systematic review is to assess the effectiveness of regulatory, environmental and educational interventions for reducing blood lead levels (BLLs) and associated health outcomes in children, pregnant women and the general population. Searches were run in MEDLINE, EMBASE and the Global Health Library up until August 2015. Studies were eligible for inclusion if they assessed the impact of regulatory, environmental or educational interventions, stand-alone or in combination, on BLLs among children, pregnant women or the general population through randomized controlled trials (RCT), controlled before-after (CBA), interrupted time series (ITS), uncontrolled before-after (UBA) or repeated cross-sectional studies. Studies assessing the impact of interventions to reduce exposure to lead in paint or household dust as well as studies concerned exclusively with environmental concentrations of lead were not included. As documented in a detailed protocol, screening, data extraction and quality appraisal were largely undertaken according to Cochrane standards. Harvest plots were used to graphically summarize evidence of effectiveness. The searches yielded 6466 unique records, of which five met our eligibility criteria; two additional eligible studies were identified by experts. We did not find any studies regarding the effectiveness of regulatory, educational or environmental interventions targeting exposure to lead in consumer products. Evidence regarding the effectiveness of interventions in reducing BLLs from exposures through drinking water is limited in both quantity and quality. Stand-alone targeted educational interventions showed no statistically significant reductions in children's BLL (two RCT) when compared to general educational interventions. Likewise, instructing women to reduce or eliminate lead-contaminated drinking water showed no effect on BLL (one RCT). Stand-alone environmental interventions appeared more promising in reducing BLL (three UBA). Combining educational and environmental interventions and targeting multiple settings may be effective in reducing BLL, as suggested by one uncontrolled before-after study. No studies examining the effectiveness of regulatory interventions were found. The limited quantity and quality of the evidence measuring BLL and associated health outcomes points to an urgent need for more robust research into the effectiveness of interventions to reduce lead exposure from consumer products and drinking water, especially for regulatory interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Removal of cyanobacterial toxins by sediment passage

NASA Astrophysics Data System (ADS)

Gruetzmacher, G.; Boettcher, G.; Chorus, I.; Bartel, H.

2003-04-01

Cyanbacterial toxins ("Cyanotoxins") comprise a wide range of toxic substances produced by cyanobacteria ("blue-green algae"). Cyanobacteria occur in surface water word wide and can be found in high concentrations during so-called algal blooms when conditions are favourable (e.g. high nutrient levels, high temperatures). Some cyanobacteria produce hepato- or neurotoxins, of which the hepatotoxic microcystins are the most common in Germany. The WHO guideline value for drinking water was set at 1 μg/L. However, maximum concentrations in surface water can reach 25 mg/L, so that a secure method for toxin elimination has to be found when this water is used as source water for drinking water production. In order to assess if cyanotoxins can be removed by sediment passage the German Federal Environmental Agency (UBA) conducted laboratory- and field scale experiments as well as observations on bank filtration field sites. Laboratory experiments (batch- and column experiments for adsorption and degradation parameters) were conducted in order to vary a multitude of experimental conditions. These experiments were followed by field scale experiments on the UBA's experimental field in Berlin. This plant offers the unique possibility to conduct experiments on the behaviour of various agents - such as harmful substances - during infiltration and bank filtration under well-defined conditions on a field scale, and without releasing these substances to the environment. Finally the development of microcystin concentrations was observed between infiltrating surface water and a drinking water well along a transsecte of observation wells. The results obtained show that infiltration and bank filtration normally seem to be secure treatment methods for source water contaminated by microcystins. However, elimination was shown to be difficult under the following circumstances: - dying cyanobacterial population due to insufficient light and / or nutrients, low temperatures or application of algizides (high amount of extracellular microcystins), - sandy material with low shares of clay and silt (little adsorption), - low temperatures (delayed biodegradation), - anoxic conditions (delayed biodegradation), - missing clogging layer or "schmutzdecke" (little bacteria), - no previous contact to microcystins (non adapted bacteria). It is therefore the aim of a new project financed by the KompetenzZentrum Wasser Berlin (KWB) to focus on these critical circumstances in order to find out how to optimise artificial recharge and bank filtration regarding microcystin elimination.

Bone Marrow Aspirate Concentrate in Combination With Intravenous Iloprost Increases Bone Healing in Patients With Avascular Necrosis of the Femoral Head: A Matched Pair Analysis.

PubMed

Pilge, Hakan; Bittersohl, Bernd; Schneppendahl, Johannes; Hesper, Tobias; Zilkens, Christoph; Ruppert, Martin; Krauspe, Rüdiger; Jäger, Marcus

2016-11-17

With disease progression, avascular necrosis (AVN) of the femoral head may lead to a collapse of the articular surface. The exact pathophysiology of AVN remains unclear, although several conditions are known that can result in spontaneous cell death, leading to a reduction of trabecular bone and the development of AVN. Hip AVN treatment is stage-dependent in which two main stages of the disease can be distinguished: pre-collapse (ARCO 0-II) and post-collapse stage (ARCO III-IV, crescent sign). In the pre-collapse phase, core decompression (CD), with or without the addition of bone marrow ( e.g . bone marrow aspirate concentrate, BMAC) or bone graft, is a common treatment alternative. In the post-collapse phase, THA (total hip arthroplasty) must be performed in most of the patients. In addition to surgical treatment, the intravenous application of Iloprost has been shown to have a curative potential and analgesic effect. From October 2009 to October 2014, 49 patients with AVN (stages I-III) were treated with core decompression at our institution. All patients were divided into group A (CD + BMAC) and group B (CD alone). Of these patients, 20 were included in a matched pair analysis. The patients were matched to age, gender, ARCO-stage, Kerboul combined necrotic angle, the cause of AVN, and whether Iloprost-therapy was performed. The Merle d'Aubigné Score and the Kerboul combined necrotic angle in a-p and lateral radiographs were evaluated pre- and postoperatively. The primary endpoint was a total hip arthroplasty. In group A, two patients needed THA while in group B four patients were treated with THA. In group A, the Merle d'Aubigné Score improved from 13.5 (pre-operatively) to 15.3 (postoperatively). In group B there was no difference between the pre- (14.3) and postoperative (14.1) assessment. The mean of the Kerboul angle showed no difference in both groups compared pre- to postoperatively (group A: pre-op 212°, postop 220°, group B: pre-op 213, postop 222°). Regarding radiographic evaluation, the interobserver variability revealed a moderate agreement between two raters regarding the pre-(ICC 0.594) and postoperative analysis (ICC 0.604).This study demonstrates that CD in combination with the application of autologous bone marrow aspirate concentrate into the femoral head seems to be a safe and efficient treatment alternative in the early stages of AVN of the femoral head when compared to CD alone.

Treatment of trochanteric fractures with the gamma3 nail - methodology and early results of a prospective consecutive monitored clinical case series.

PubMed

A C, Unger; E, Wilde; B, Kienast; C, Jürgens; A P, Schulz

2014-01-01

There is only sparse data on clinical results and complications of the third-generation Gamma nailing system (Gamma3, Stryker). Therefore, we started a large multi-centre case series in 2008. The aim of this paper is to present the study design and early results of a single arm of a prospective, consecutive, monitored, post-market follow-up evaluation of Gamma3 nails. From September 2009 to January 2012, 154 consecutive patients with an average age of 80 ± 1.43 years (50-99 years) and a trochanteric femoral fracture were included in the local arm of the trial. All patients that fulfilled the inclusion criteria were treated with a Gamma3 nail. Preoperative variables included age, gender, fracture classification, walking ability (Merle d'Aubigné score), daily activity level (retrospective Zuckerman score), ASA rating of operative risk, waiting time for operation, use of walker or crutches and body mass index (BMI). Skin-to-skin time, fluoroscopy time, blood loss, intraoperative complications and device information were recorded for each patient. Follow-up postoperative assessment was undertaken at 4, 12 and 24 months. Hip range of motion, pain around the hip and the tight, walking ability (Merle d'Aubigné score, Sahlgrenska mobility score) and management of daily life (Zuckerman score) were used to evaluate the outcome. The descriptive data of age, gender, BMI, ASA classification, fracture type and skin-to-skin time is similar to other studies. Median fluoroscopy time was 62 seconds (range: 4-225 seconds) and significantly shorter in closed reductions. No intraoperative implant-related complication was recorded. A cut-out of the leg-screw during assessment period occurred in 2.6% patients (n = 4). At the 12-month assessment two (1.8%) non-unions were identified and two patients (1.8%) had broken the femoral shaft below the 180 mm nail after a fall. Analysis of the scores showed significantly declined mobility and activity in daily life four months after operation which increased significantly from four to 12 months and increased slightly between 12 and 24 months after fracture. A low implant-associated complication rate was achieved in geriatric patients with trochanteric femoral fractures using the Gamma3 nail. A better outcome concerning mobility, activity in daily life and complications compared to the Gamma2 nail could not be found in comparison to historic data.

Analyses of transients for an 800 MW-class accelerator driven transmuter with fertile-free fuels

NASA Astrophysics Data System (ADS)

Maschek, Werner; Suzuki, Tohru; Chen, Xue-Nong; Rineiski, Andrei; Matzerath Boccaccini, Claudia; Mori, Magnus; Morita, Koji

2006-06-01

In the FUTURE Program, the development and application of fertile-free fuels for Accelerator Driven Transmuters (ADTs) has been advanced. To assess the reactor performance and safety behavior of an ADT with so-called dedicated fuels, various transient cases for an 800 MW-class Pb/Bi-cooled ADT were investigated using the SIMMER-III code. The FUTURE ADT also served as vehicle to develop and test ideas on a safety concept for such transmuters. After an extensive ranking procedure, a CERCER fuel with an MgO matrix and a CERMET fuel with a Mo-92 matrix were chosen. The transient scenarios shown here are: spurious beam trip (BT), unprotected loss of flow (ULOF) and unprotected blockage accident (UBA). Since the release of fission gas and helium after cladding failure could induce a significant positive reactivity, the gas-blowdown was investigated for the transient scenarios. The present analyses showed that power excursions could be avoided by the fuel sweep-out from the core under severe accident conditions.

Protein Frustratometer 2: a tool to localize energetic frustration in protein molecules, now with electrostatics.

PubMed

Parra, R Gonzalo; Schafer, Nicholas P; Radusky, Leandro G; Tsai, Min-Yeh; Guzovsky, A Brenda; Wolynes, Peter G; Ferreiro, Diego U

2016-07-08

The protein frustratometer is an energy landscape theory-inspired algorithm that aims at localizing and quantifying the energetic frustration present in protein molecules. Frustration is a useful concept for analyzing proteins' biological behavior. It compares the energy distributions of the native state with respect to structural decoys. The network of minimally frustrated interactions encompasses the folding core of the molecule. Sites of high local frustration often correlate with functional regions such as binding sites and regions involved in allosteric transitions. We present here an upgraded version of a webserver that measures local frustration. The new implementation that allows the inclusion of electrostatic energy terms, important to the interactions with nucleic acids, is significantly faster than the previous version enabling the analysis of large macromolecular complexes within a user-friendly interface. The webserver is freely available at URL: http://frustratometer.qb.fcen.uba.ar. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Correlation of Chemical and Physical Test Data for the Environmental Ageing of Tefzel (ETFE)

NASA Technical Reports Server (NTRS)

Morgan, G. J.; Campion, R. P.

1996-01-01

In a similar approach to that used for the previously issued correlation report for Coflon (CAPP/M.10), this report aims to identify any correlations between mechanical property changes and chemical/morphological changes for Tefzel, using information supplied in other MERL and TRI project reports (plus latest data which will be included in final reports for Phase 1). Differences identified with Coflon behaviour will be of scientific interest as well as appropriate to project applications, as Tefzel and Coflon are chemical isomers. Owing to the considerable chemical resistance of Tefzel, much of its testing so far has been based on mechanical properties. Where changes have occurred, chemical analysis can now be targeted more effectively. Relevant test data collated here include: tensile modulus and related properties, permeation coefficients, % crystallinity, and other observations where significant. Fluids based on methanol and amine (Fluid G), a mixture of methane, carbon dioxide and hydrogen sulphide gases plus an aqueous amine solution (Fluid F), and an aromatic oil mix of heptane, cyclohexane, toluene and I-propanol (Fluid 1) have affected Tefzel to varying degrees, and are discussed in some detail herein.

Correlation of Chemical and Physical Test Data for the Environmental Ageing of Tefzel (ETFE). Revised

NASA Technical Reports Server (NTRS)

Morgan, G. J.; Campion, R. P.

1997-01-01

In a similar approach to that used for the previously issued correlation report for Coflon (CAPP/M.10), this report aims to identify any correlations between mechanical property changes and chemical/morphological changes for Tefzel, using information supplied in other MERL and TRI project reports. Differences identified with Coflon behaviour will be of scientific interest as well as appropriate to project applications, as Tefzel and Coflon are chemical isomers. Owing to the considerable chemical resistance of Tefzel, much of its testing so far has been based on mechanical properties. Where changes have occurred, chemical analysis can now be targeted more effectively. Relevant test data collated here include: tensile modulus and related properties, permeation coefficients, % crystallinity, some crack growth resistance measurements, and other observations where significant. Fluids based on methanol and amine (Fluid G), a mixture of methane, carbon dioxide and hydrogen sulphide gases plus an aqueous amine solution (Fluid F), and an aromatic oil mix of heptane, cyclohexane, toluene and 1-propanol (Fluid I) have affected Tefzel to varying degrees, and are discussed in some detail herein.

Prevalence, heritability and genetic correlations of congenital sensorineural deafness and pigmentation phenotypes in the Border Collie.

PubMed

De Risio, Luisa; Lewis, Tom; Freeman, Julia; de Stefani, Alberta; Matiasek, Lara; Blott, Sarah

2011-06-01

The objectives of this study were to estimate prevalence, heritability and genetic correlations of congenital sensorineural deafness (CSD) and pigmentation phenotypes in the Border Collie. Entire litters of Border Collies that presented to the Animal Health Trust (1994-2008) for assessment of hearing status by brain stem auditory evoked response (BAER) at 4-10 weeks of age were included. Heritability and genetic correlations were estimated using residual maximum likelihood (REML). Of 4143 puppies that met the inclusion criteria, 97.6% had normal hearing status, 2.0% were unilaterally deaf and 0.4% were bilaterally deaf. Heritability of deafness as a trichotomous trait (normal/unilaterally deaf/bilaterally deaf) was estimated at 0.42 using multivariate analysis. Genetic correlations of deafness with iris colour and merle coat colour were 0.58 and 0.26, respectively. These results indicate that there is a significant genetic effect on CSD in Border Collies and that some of the genes determining deafness also influence pigmentation phenotypes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Summary Report for the Evaluation of Current QA Processes Within the FRMAC FAL and EPA MERL.

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

Shanks, Sonoya T.; Redding, Ted; Jaussi, Lynn

The Federal Radiological Monitoring and Assessment Center (FRMAC) relies on accurate and defensible analytical laboratory data to support its mission. Therefore, FRMAC must ensure that the environmental analytical laboratories providing analytical services maintain an ongoing capability to provide accurate analytical results to DOE. It is undeniable that the more Quality Assurance (QA) and Quality Control (QC) measures required of the laboratory, the less resources that are available for analysis of response samples. Being that QA and QC measures in general are understood to comprise a major effort related to a laboratory’s operations, requirements should only be considered if they aremore » deemed “value-added” for the FRMAC mission. This report provides observations of areas for improvement and potential interoperability opportunities in the areas of Batch Quality Control Requirements, Written Communications, Data Review Processes, Data Reporting Processes, along with the lessons learned as they apply to items in the early phase of a response that will be critical for developing a more efficient, integrated response for future interactions between the FRMAC and EPA assets.« less

From Intensity Profile to Surface Normal: Photometric Stereo for Unknown Light Sources and Isotropic Reflectances.

PubMed

Lu, Feng; Matsushita, Yasuyuki; Sato, Imari; Okabe, Takahiro; Sato, Yoichi

2015-10-01

We propose an uncalibrated photometric stereo method that works with general and unknown isotropic reflectances. Our method uses a pixel intensity profile, which is a sequence of radiance intensities recorded at a pixel under unknown varying directional illumination. We show that for general isotropic materials and uniformly distributed light directions, the geodesic distance between intensity profiles is linearly related to the angular difference of their corresponding surface normals, and that the intensity distribution of the intensity profile reveals reflectance properties. Based on these observations, we develop two methods for surface normal estimation; one for a general setting that uses only the recorded intensity profiles, the other for the case where a BRDF database is available while the exact BRDF of the target scene is still unknown. Quantitative and qualitative evaluations are conducted using both synthetic and real-world scenes, which show the state-of-the-art accuracy of smaller than 10 degree without using reference data and 5 degree with reference data for all 100 materials in MERL database.

SymPS: BRDF Symmetry Guided Photometric Stereo for Shape and Light Source Estimation.

PubMed

Lu, Feng; Chen, Xiaowu; Sato, Imari; Sato, Yoichi

2018-01-01

We propose uncalibrated photometric stereo methods that address the problem due to unknown isotropic reflectance. At the core of our methods is the notion of "constrained half-vector symmetry" for general isotropic BRDFs. We show that such symmetry can be observed in various real-world materials, and it leads to new techniques for shape and light source estimation. Based on the 1D and 2D representations of the symmetry, we propose two methods for surface normal estimation; one focuses on accurate elevation angle recovery for surface normals when the light sources only cover the visible hemisphere, and the other for comprehensive surface normal optimization in the case that the light sources are also non-uniformly distributed. The proposed robust light source estimation method also plays an essential role to let our methods work in an uncalibrated manner with good accuracy. Quantitative evaluations are conducted with both synthetic and real-world scenes, which produce the state-of-the-art accuracy for all of the non-Lambertian materials in MERL database and the real-world datasets.

Branch and bound algorithm for accurate estimation of analytical isotropic bidirectional reflectance distribution function models.

PubMed

Yu, Chanki; Lee, Sang Wook

2016-05-20

We present a reliable and accurate global optimization framework for estimating parameters of isotropic analytical bidirectional reflectance distribution function (BRDF) models. This approach is based on a branch and bound strategy with linear programming and interval analysis. Conventional local optimization is often very inefficient for BRDF estimation since its fitting quality is highly dependent on initial guesses due to the nonlinearity of analytical BRDF models. The algorithm presented in this paper employs L₁-norm error minimization to estimate BRDF parameters in a globally optimal way and interval arithmetic to derive our feasibility problem and lower bounding function. Our method is developed for the Cook-Torrance model but with several normal distribution functions such as the Beckmann, Berry, and GGX functions. Experiments have been carried out to validate the presented method using 100 isotropic materials from the MERL BRDF database, and our experimental results demonstrate that the L₁-norm minimization provides a more accurate and reliable solution than the L₂-norm minimization.

Sequential fitting-and-separating reflectance components for analytical bidirectional reflectance distribution function estimation.

PubMed

Lee, Yu; Yu, Chanki; Lee, Sang Wook

2018-01-10

We present a sequential fitting-and-separating algorithm for surface reflectance components that separates individual dominant reflectance components and simultaneously estimates the corresponding bidirectional reflectance distribution function (BRDF) parameters from the separated reflectance values. We tackle the estimation of a Lafortune BRDF model, which combines a nonLambertian diffuse reflection and multiple specular reflectance components with a different specular lobe. Our proposed method infers the appropriate number of BRDF lobes and their parameters by separating and estimating each of the reflectance components using an interval analysis-based branch-and-bound method in conjunction with iterative K-ordered scale estimation. The focus of this paper is the estimation of the Lafortune BRDF model. Nevertheless, our proposed method can be applied to other analytical BRDF models such as the Cook-Torrance and Ward models. Experiments were carried out to validate the proposed method using isotropic materials from the Mitsubishi Electric Research Laboratories-Massachusetts Institute of Technology (MERL-MIT) BRDF database, and the results show that our method is superior to a conventional minimization algorithm.

Outreach geology with the "balades géologiques" project based on smartphone technology

NASA Astrophysics Data System (ADS)

Egoroff, Grégoire; de Wever, Patrick; Cornee, Annie

2014-05-01

Initially launched with printed booklets (in 2009), the "Balades géologiques" project is now developing new access. In the late 90's, the project was originally using strolls in centre of city to present geology through building stones. Indeed, old or new buildings use rocks that can be used to introduce the discipline to a large public. A stroll in a city is a good opportunity to introduce various concepts of geology, such as sedimentology, petrography, topography, geotechnics etc. For example, in the city of Paris, one of the underground lines becomes sub-aerial on a portion which is famous because of the point of view of the city it offers. People generally ignores this is to step over the valley of one the Seine affluent (the Bièvre river), as the river itself is now buried. This example is a good way to introduce geomorphological concept. We used strolls with general public in towns for many years, before we started publishing these strolls as booklets. After 5 years, we have now established booklets of the "Balades géologiques" for 18 towns all over France. Others are currently in redaction. To go ahead with this project, we decided to take advantage of new technologies. We developed apps on smartphone to diffuse some geological information. A pilot trial was conducted in the city of Dourdan (south of Paris) with the development of media for a smartphone application, but also for the GoogleEarth interface. We used a database developed by the university of Nice (France) to diffuse some description of buildings on a map. This database uses the free Wikitude application for smartphone. We have now four projects under development. The database is functional and is improving each year. We will present the booklet collection and the way we can diffuse various geologically-relevant information via the apps. Our goal here is to make them as accessible and attractive as possible for any audience and to show that geology does not belong to a few "insiders". Billet G., Bonnefoy B., Houssaye A., De Wever P. & Merle D. (2008) - Promenade géologique à Etampes. Coll. balades géologiques, SGF-MNHN-BRGM, 30 pages. Egoroff G., De Wever P., Merle D. & Métivier B. (2011) - Promenade géologique à Dourdan. Biotope, Mèze - MNHN, Paris - BRGM, Orléans (Collection Balades géologiques), 38 pages. Nouvellet S., Egoroff G. & De Wever P. (2013) - Virtual Milly-la-Forêt Geological stroll, online. Android app Wikitude, « ID Bio-Balades géologiques » project "Milly-la-Forêt".

The RasGAP Proteins Ira2 and Neurofibromin Are Negatively Regulated by Gpb1 in Yeast and ETEA in Humans▿

PubMed Central

Phan, Vernon T.; Ding, Vivianne W.; Li, Fenglei; Chalkley, Robert J.; Burlingame, Alma; McCormick, Frank

2010-01-01

The neurofibromatosis type 1 (NF1) gene encodes the GTPase-activating protein (GAP) neurofibromin, which negatively regulates Ras activity. The yeast Saccharomyces cerevisiae has two neurofibromin homologs, Ira1 and Ira2. To understand how these proteins are regulated, we utilized an unbiased proteomics approach to identify Ira2 and neurofibromin binding partners. We demonstrate that the Gpb1/Krh2 protein binds and negatively regulates Ira2 by promoting its ubiquitin-dependent proteolysis. We extended our findings to show that in mammalian cells, the ETEA/UBXD8 protein directly interacts with and negatively regulates neurofibromin. ETEA contains both UBA and UBX domains. Overexpression of ETEA downregulates neurofibromin in human cells. Purified ETEA, but not a mutant of ETEA that lacks the UBX domain, ubiquitinates the neurofibromin GAP-related domain in vitro. Silencing of ETEA expression increases neurofibromin levels and downregulates Ras activity. These findings provide evidence for conserved ubiquitination pathways regulating the RasGAP proteins Ira2 (in yeast) and neurofibromin (in humans). PMID:20160012

Autophagic Regulation of p62 is Critical for Cancer Therapy

PubMed Central

Islam, Md. Ariful; Sooro, Mopa Alina

2018-01-01

Sequestosome1 (p62/SQSTM 1) is a multidomain protein that interacts with the autophagy machinery as a key adaptor of target cargo. It interacts with phagophores through the LC3-interacting (LIR) domain and with the ubiquitinated protein aggregates through the ubiquitin-associated domain (UBA) domain. It sequesters the target cargo into inclusion bodies by its PB1 domain. This protein is further the central hub that interacts with several key signaling proteins. Emerging evidence implicates p62 in the induction of multiple cellular oncogenic transformations. Indeed, p62 upregulation and/or reduced degradation have been implicated in tumor formation, cancer promotion as well as in resistance to therapy. It has been established that the process of autophagy regulates the levels of p62. Autophagy-dependent apoptotic activity of p62 is recently being reported. It is evident that p62 plays a critical role in both autophagy and apoptosis. Therefore in this review we discuss the role of p62 in autophagy, apoptosis and cancer through its different domains and outline the importance of modulating cellular levels of p62 in cancer therapeutics. PMID:29738493

Ubiquitylation of p62/sequestosome1 activates its autophagy receptor function and controls selective autophagy upon ubiquitin stress

PubMed Central

Peng, Hong; Yang, Jiao; Li, Guangyi; You, Qing; Han, Wen; Li, Tianrang; Gao, Daming; Xie, Xiaoduo; Lee, Byung-Hoon; Du, Juan; Hou, Jian; Zhang, Tao; Rao, Hai; Huang, Ying; Li, Qinrun; Zeng, Rong; Hui, Lijian; Wang, Hongyan; Xia, Qin; Zhang, Xuemin; He, Yongning; Komatsu, Masaaki; Dikic, Ivan; Finley, Daniel; Hu, Ronggui

2017-01-01

Alterations in cellular ubiquitin (Ub) homeostasis, known as Ub stress, feature and affect cellular responses in multiple conditions, yet the underlying mechanisms are incompletely understood. Here we report that autophagy receptor p62/sequestosome-1 interacts with E2 Ub conjugating enzymes, UBE2D2 and UBE2D3. Endogenous p62 undergoes E2-dependent ubiquitylation during upregulation of Ub homeostasis, a condition termed as Ub+ stress, that is intrinsic to Ub overexpression, heat shock or prolonged proteasomal inhibition by bortezomib, a chemotherapeutic drug. Ubiquitylation of p62 disrupts dimerization of the UBA domain of p62, liberating its ability to recognize polyubiquitylated cargoes for selective autophagy. We further demonstrate that this mechanism might be critical for autophagy activation upon Ub+ stress conditions. Delineation of the mechanism and regulatory roles of p62 in sensing Ub stress and controlling selective autophagy could help to understand and modulate cellular responses to a variety of endogenous and environmental challenges, potentially opening a new avenue for the development of therapeutic strategies against autophagy-related maladies. PMID:28322253

Autophagic Regulation of p62 is Critical for Cancer Therapy.

PubMed

Islam, Md Ariful; Sooro, Mopa Alina; Zhang, Pinghu

2018-05-08

Sequestosome1 (p62/SQSTM 1) is a multidomain protein that interacts with the autophagy machinery as a key adaptor of target cargo. It interacts with phagophores through the LC3-interacting (LIR) domain and with the ubiquitinated protein aggregates through the ubiquitin-associated domain (UBA) domain. It sequesters the target cargo into inclusion bodies by its PB1 domain. This protein is further the central hub that interacts with several key signaling proteins. Emerging evidence implicates p62 in the induction of multiple cellular oncogenic transformations. Indeed, p62 upregulation and/or reduced degradation have been implicated in tumor formation, cancer promotion as well as in resistance to therapy. It has been established that the process of autophagy regulates the levels of p62. Autophagy-dependent apoptotic activity of p62 is recently being reported. It is evident that p62 plays a critical role in both autophagy and apoptosis. Therefore in this review we discuss the role of p62 in autophagy, apoptosis and cancer through its different domains and outline the importance of modulating cellular levels of p62 in cancer therapeutics.

Prediction of Spontaneous Protein Deamidation from Sequence-Derived Secondary Structure and Intrinsic Disorder.

PubMed

Lorenzo, J Ramiro; Alonso, Leonardo G; Sánchez, Ignacio E

2015-01-01

Asparagine residues in proteins undergo spontaneous deamidation, a post-translational modification that may act as a molecular clock for the regulation of protein function and turnover. Asparagine deamidation is modulated by protein local sequence, secondary structure and hydrogen bonding. We present NGOME, an algorithm able to predict non-enzymatic deamidation of internal asparagine residues in proteins in the absence of structural data, using sequence-based predictions of secondary structure and intrinsic disorder. Compared to previous algorithms, NGOME does not require three-dimensional structures yet yields better predictions than available sequence-only methods. Four case studies of specific proteins show how NGOME may help the user identify deamidation-prone asparagine residues, often related to protein gain of function, protein degradation or protein misfolding in pathological processes. A fifth case study applies NGOME at a proteomic scale and unveils a correlation between asparagine deamidation and protein degradation in yeast. NGOME is freely available as a webserver at the National EMBnet node Argentina, URL: http://www.embnet.qb.fcen.uba.ar/ in the subpage "Protein and nucleic acid structure and sequence analysis".

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens

PubMed Central

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo

2018-01-01

Abstract Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. PMID:29106651

Early radiological and functional outcomes for a cementless press-fit design modular femoral stem revision system.

PubMed

Hancock, Douglas S; Sharplin, Paul K; Larsen, Peter D; Phillips, Fredrick Ts

2018-05-01

To assess early radiological and functional outcomes of revision hip surgery with a cementless press-fit design femoral stem. A retrospective review of 48 consecutive revision total hip replacements using the RECLAIM revision hip system, between October 2012 and August 2015. Radiographic assessment was undertaken with serial anteroposterior (AP) X-rays of the pelvis. Risk factors for subsidence were evaluated. Prospective clinical follow up was performed on 21 patients to assess functional outcomes. Mean stem subsidence was 1.1 mm (95% confidence interval[CI]: 0.63-1.57). Median follow up of 12 months. An inverse relationship was observed between level of subsidence and femoral stem diameter r = -0.45, p = 0.001. Subsidence at the time of follow-up assessment was correlated with initial subsidence (correlation coefficient rho 0.69, p = 0.001). The mean Merle d'Aubigne score at the latest follow up was 14.2 (range 8-17). The mean OHS was 34.1 (range 15-48). Early radiological and functional outcomes for the RECLAIM revision system showed very low levels of subsidence and good functional outcomes. There was an association with smaller diameter femoral stems and greater levels of subsidence.

Biodegradable implants for Pipkin fractures.

PubMed

Prokop, Axel; Helling, Hanns-Joachim; Hahn, Ulrich; Udomkaewkanjana, Chira; Rehm, Klaus Emil

2005-03-01

The current study was designed to clarify whether biodegradable poly-L/DL lactide pins provide an operative alternative for fixation of Pipkin fractures. Nine patients with Pipkin fractures (one with Pipkin Type I, one with Pipkin Type II, and seven with Pipkin Type IV fractures) were treated surgically between 1996 and 2002. In all patients, the femoral head fractures were fixed with biodegradable, 2.7-mm and 2.0-mm polylactide pins. Eight patients were followed up for an average of 54.2 months. One patient died before the final followup. Eight fractures healed uneventfully. In one patient, a persisting femoral head defect led to posttraumatic arthritis requiring insertion of a femoral endoprosthesis at 1 year. The average range of motion of the affected hips of all patients at followup was 109 degrees -0 degrees -0 degrees in flexion and extension. External and internal rotation averaged 37 degrees -0 degrees -29 degrees . One patient had Brooker Grade I heterotopic ossification develop, and another had a Grade II heterotopic develop. Merle d'Aubigne and Postel ratings showed two excellent and five satisfactory results (average score, 13.1). Adverse effects from the polylactide implants were not observed. Pipkin fractures can be fixed successfully with biodegradable polylactide pins.

Total hip arthroplasty of dysplastic hip after previous Chiari pelvic osteotomy.

PubMed

Minoda, Yukihide; Kadowaki, Toru; Kim, Mitsunari

2006-08-01

Many reports have suggested that Chiari pelvic osteotomy would improve the results of acetabular component placement and fixation in subsequent total hip arthroplasty. However, little is known concerning the biomechanical, radiological, and clinical effects of Chiari pelvic osteotomy on subsequent total hip arthroplasty. Ten total hip arthroplasties for developmental dysplasia of the hip after previous Chiari pelvic osteotomy (Chiari group) were compared with 20 total hip arthroplasties for developmental dysplasia of the hip without previous surgery (control group). Preoperative patient demographic data and operative technique were well matched between the groups. The mean duration of follow-up was 3.0 years. Biomechanical, radiological, and clinical evaluations were performed. No acetabular or femoral components exhibited loosening. All patients had good or excellent clinical score according to the Merle d'Aubigne-Postel rating system at the most recent follow-up. Abductor force and joint force were smaller in the Chiari group, although long operative time, more blood loss, and verticalization of joint force were noted in this group. This limited study suggested that Chiari pelvic osteotomy changed the biomechanical features of the hip joint, and that this alteration might have compromised subsequent total hip arthroplasty.

Aerosol particle properties in a South American megacity

NASA Astrophysics Data System (ADS)

Ulke, Ana; Torres-Brizuela, Marcela; Raga, Graciela; Baumgardner, Darrel; Cancelada, Marcela

2015-04-01

The subtropical city of Buenos Aires is located on the western shore of Río de la Plata, on the southeastern coast of Argentina. It is the second largest metropolitan area in South America, with a population density of around 14 thousand people per km2. When all 24 counties of the Great Buenos Aires Metropolitan Area are included it is the third-largest conurbation in Latin America, with a population of around fifteen million inhabitants. The generalized worldwide trend to concentrate human activities in urban regions that continue to expand in area, threatens the local and regional environment. Air pollution in the Buenos Aires airshed is due to local sources (mainly the mobile sources, followed by the electric power plants and some industries) and to distant sources (like biomass burning, dust, marine aerosols and occasionally volcanic ash) whose products arrive in the city area due to the regional transport patterns. Previous research suggests that ambient aerosol particle concentrations should be considered an air quality problem. A field campaign was conducted in Buenos Aires in 2011 in order to characterize some aerosol particles properties measured for the first time in the city. Measurements began in mid- April and continued until December. The field observations were done in a collaborative effort between the Universities of Mexico (UNAM) and Buenos Aires (UBA). A suite of instruments was installed on the roof of an UBA laboratory and classroom buildings (34.54° S, 58.44° W) at an altitude of approximately 30 m above sea level. The measurements included the number concentration of condensation nuclei (CN) larger than approximately 50 nm, the mass concentration of particle-bound polycyclic aromatic hydrocarbons (PPAH), the scattering (Bscat) and absorption (Babs) coefficients at 550 nm and the vertical profiles of backscattered light from aerosols at a wavelength of 910 nm using a ceilometer. In addition, a weather station recorded the meteorological state of the atmosphere. During the campaign, the eruption of the Puyehue-Cordon Caulle complex in Southern Chile took place and the plume passed several times over the measurement site. Backward trajectories and the analysis of the prevailing synoptic environment was used in order to relate the measurements with the air mass history and to detect the regional contributions to the aerosol load in the city. Strong correlations between the CN, PPAH and black carbon suggest that the majority of particles come from combustion (vehicular traffic and the nearby power plant). The higher values were observed during the cold season, with maximum CN number concentration reaching 55000 cm-3, and the most frequent concentrations varying from 800 cm-3 to 11000 cm-3. The highest recorded concentrations of PPAH and BC were 500 ng m-3 and 400 ng m-3, respectively.

Constraints on the timing of Co-Cu ± Au mineralization in the Blackbird district, Idaho, using SHRIMP U-Pb ages of monazite and xenotime plus zircon ages of related Mesoproterozoic orthogneisses and metasedimentary rocks

USGS Publications Warehouse

Aleinikoff, John N.; Slack, John F.; Lund, Karen; Evans, Karl V.; Fanning, C. Mark; Mazdab, Frank K.; Wooden, Joseph L.; Pillers, Renee M.

2012-01-01

The Blackbird district, east-central Idaho, contains the largest known Co reserves in the United States. The origin of strata-hosted Co-Cu ± Au mineralization at Blackbird has been a matter of controversy for decades. In order to differentiate among possible genetic models for the deposits, including various combinations of volcanic, sedimentary, magmatic, and metamorphic processes, we used U-Pb geochronology of xenotime, monazite, and zircon to establish time constraints for ore formation. New age data reported here were obtained using sensitive high resolution ion microprobe (SHRIMP) microanalysis of (1) detrital zircons from a sample of Mesoproterozoic siliciclastic metasedimentary country rock in the Blackbird district, (2) igneous zircons from Mesoproterozoic intrusions, and (3) xenotime and monazite from the Merle and Sunshine prospects at Blackbird. Detrital zircon from metasandstone of the biotite phyllite-schist unit has ages mostly in the range of 1900 to 1600 Ma, plus a few Neoarchean and Paleoproterozoic grains. Age data for the six youngest grains form a coherent group at 1409 ± 10 Ma, regarded as the maximum age of deposition of metasedimentary country rocks of the central structural domain. Igneous zircons from nine samples of megacrystic granite, granite augen gneiss, and granodiorite augen gneiss that crop out north and east of the Blackbird district yield ages between 1383 ± 4 and 1359 ± 7 Ma. Emplacement of the Big Deer Creek megacrystic granite (1377 ± 4 Ma), structurally juxtaposed with host rocks in the Late Cretaceous ca. 5 km north of Blackbird, may have been involved in initial deposition of rare earth elements (REE) minerals and, possibly, sulfides. In situ SHRIMP ages of xenotime and monazite in Co-rich samples from the Merle and Sunshine prospects, plus backscattered electron imagery and SHRIMP analyses of trace elements, indicate a complex sequence of Mesoproterozoic and Cretaceous events. On the basis of textural relationships observed in thin section, xeno-time and cobaltite formed during multiple episodes. The oldest age for xenotime (1370 ± 4 Ma), determined on oscillatory-zoned cores, may date the time of initial cobaltite formation, and provides a minimum age for the host metasedimentary rocks. Additional Proterozoic xenotime growth events occurred at 1315 to 1270 Ma and ca. 1050 Ma. Other xenotime grains and rims grew in conjunction with cobaltite during Cretaceous metamorphism. However, ages of these growth episodes cannot be precisely determined due to matrix effects on 206Pb/238U data for xenotime. Monazite, some of which encloses cobaltite, uniformly has Cretaceous ages that mainly are 110 ± 3 and 92 ± 5 Ma. These data indicate that xenotime, monazite, and cobaltite were extensively mobilized and precipitated during Middle to Late Cretaceous metamorphic events.

[On the founders of the Institute of Mathematics and Physics, University of Bahia].

PubMed

Dias, A L

The reduced number of female students of mathematics at the University of Bahia School of Philosophy (Faculdade de Filosofia, Universidade da Bahia - FF/UBa) is quite surprising. To date, they are concentrated in areas traditionally viewed as feminine whereas men predominate in the mathematical fields. I have examined interview data from a few women who graduated in mathematics and went on to teach at the University of Bahia School of Mathematics (Faculdade de Filosofia - FF) and at the Institute of Mathematics and Physics (Instituto de Matemática e Física - IMF), where they were soon to outnumber men and constitute the majority of the mathematics teaching staff. In this study, I have investigated the course of their careers over time: from their early student days, through their time as teaching assistants and professors, and finally as founders of the Institute of Mathematics and Physics, in 1960. Special reference is made to Martha Maria de Souza Dantas, organizer of the I Brazilian Conference on Mathematics Teaching, an event which has provided the groundwork for what was to become the Institute (IMF); and to Arlete Cerqueira Lima, the mastermind behind its creation.

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens.

PubMed

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Defelipe, Lucas; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo; Turjanski, Adrián G; Fernández Do Porto, Darío

2018-01-04

Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Identification of Cellular Proteins Required for Replication of Human Immunodeficiency Virus Type 1

PubMed Central

Dziuba, Natallia; Ferguson, Monique R.; O'Brien, William A.; Sanchez, Anthony; Prussia, Andrew J.; McDonald, Natalie J.; Friedrich, Brian M.; Li, Guangyu; Shaw, Michael W.; Sheng, Jinsong; Hodge, Thomas W.; Rubin, Donald H.

2012-01-01

Abstract Cellular proteins are essential for human immunodeficiency virus type 1 (HIV-1) replication and may serve as viable new targets for treating infection. Using gene trap insertional mutagenesis, a high-throughput approach based on random inactivation of cellular genes, candidate genes were found that limit virus replication when mutated. Disrupted genes (N=87) conferring resistance to lytic infection with several viruses were queried for an affect on HIV-1 replication by utilizing small interfering RNA (siRNA) screens in TZM-bl cells. Several genes regulating diverse pathways were found to be required for HIV-1 replication, including DHX8, DNAJA1, GTF2E1, GTF2E2, HAP1, KALRN, UBA3, UBE2E3, and VMP1. Candidate genes were independently tested in primary human macrophages, toxicity assays, and/or Tat-dependent β-galactosidase reporter assays. Bioinformatics analyses indicated that several host factors present in this study participate in canonical pathways and functional processes implicated in prior genome-wide studies. However, the genes presented in this study did not share identity with those found previously. Novel antiviral targets identified in this study should open new avenues for mechanistic investigation. PMID:22404213

Identification of cellular proteins required for replication of human immunodeficiency virus type 1.

PubMed

Dziuba, Natallia; Ferguson, Monique R; O'Brien, William A; Sanchez, Anthony; Prussia, Andrew J; McDonald, Natalie J; Friedrich, Brian M; Li, Guangyu; Shaw, Michael W; Sheng, Jinsong; Hodge, Thomas W; Rubin, Donald H; Murray, James L

2012-10-01

Cellular proteins are essential for human immunodeficiency virus type 1 (HIV-1) replication and may serve as viable new targets for treating infection. Using gene trap insertional mutagenesis, a high-throughput approach based on random inactivation of cellular genes, candidate genes were found that limit virus replication when mutated. Disrupted genes (N=87) conferring resistance to lytic infection with several viruses were queried for an affect on HIV-1 replication by utilizing small interfering RNA (siRNA) screens in TZM-bl cells. Several genes regulating diverse pathways were found to be required for HIV-1 replication, including DHX8, DNAJA1, GTF2E1, GTF2E2, HAP1, KALRN, UBA3, UBE2E3, and VMP1. Candidate genes were independently tested in primary human macrophages, toxicity assays, and/or Tat-dependent β-galactosidase reporter assays. Bioinformatics analyses indicated that several host factors present in this study participate in canonical pathways and functional processes implicated in prior genome-wide studies. However, the genes presented in this study did not share identity with those found previously. Novel antiviral targets identified in this study should open new avenues for mechanistic investigation.

Monitoring autophagic flux using Ref(2)P, the Drosophila p62 ortholog.

PubMed

DeVorkin, Lindsay; Gorski, Sharon M

2014-09-02

Human p62, also known as Sequestome-1 (SQSTM1), is a multifunctional scaffold protein that contains many domains, including a Phox/Bem1P (PB1) multimerization domain, an ubiquitin-associated (UBA) domain, and a light chain 3 (LC3) recognition sequence. p62 binds ubiquitinated proteins and targets them for degradation by the proteasome. In addition, p62 directly binds LC3; this may serve as a mechanism to deliver ubiquitinated proteins for degradation by autophagy. During this process, p62 itself is degraded. The inhibition of autophagy leads to the accumulation of p62, indicating that it can be used as a marker of autophagic flux. Ref(2)P (refractory to sigma P), the Drosophila ortholog of p62, is also required for the formation of ubiquitinated protein aggregates. Ref(2)P contains a putative LC3-interacting region, and genetic inhibition of autophagy in Drosophila leads to the accumulation of Ref(2)P protein levels. Thus, like p62, Ref(2)P may serve as a marker of autophagic flux. Here we provide two procedures to examine Ref(2)P protein levels in Drosophila ovaries. © 2014 Cold Spring Harbor Laboratory Press.

Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in Archaea

DOE PAGES

Fu, Xian; Adams, Zachary; Liu, Rui; ...

2017-09-05

Methionine sulfoxide reductase A (MsrA) is an antioxidant enzyme found in all domains of life that catalyzes the reduction of methionine-S-sulfoxide (MSO) to methionine in proteins and free amino acids. We demonstrate that archaeal MsrA has a ubiquitin-like (Ubl) protein modification activity that is distinct from its stereospecific reduction of MSO residues. MsrA catalyzes this Ubl modification activity, with the Ubl-activating E1 UbaA, in the presence of the mild oxidant dimethyl sulfoxide (DMSO) and in the absence of reductant. In contrast, the MSO reductase activity of MsrA is inhibited by DMSO and requires reductant. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysismore » reveals that MsrA-dependent Ubl conjugates are associated with DNA replication, protein remodeling, and oxidative stress and include the Ubl-modified MsrA, Orc3 (Orc1/Cdc6), and Cdc48d (Cdc48/p97 AAA+ ATPase). Overall, we found archaeal MsrA to have opposing MSO reductase and Ubl modifying activities that are associated with oxidative stress responses and controlled by exposure to mild oxidant.« less

Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in Archaea

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

Fu, Xian; Adams, Zachary; Liu, Rui

Methionine sulfoxide reductase A (MsrA) is an antioxidant enzyme found in all domains of life that catalyzes the reduction of methionine-S-sulfoxide (MSO) to methionine in proteins and free amino acids. We demonstrate that archaeal MsrA has a ubiquitin-like (Ubl) protein modification activity that is distinct from its stereospecific reduction of MSO residues. MsrA catalyzes this Ubl modification activity, with the Ubl-activating E1 UbaA, in the presence of the mild oxidant dimethyl sulfoxide (DMSO) and in the absence of reductant. In contrast, the MSO reductase activity of MsrA is inhibited by DMSO and requires reductant. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysismore » reveals that MsrA-dependent Ubl conjugates are associated with DNA replication, protein remodeling, and oxidative stress and include the Ubl-modified MsrA, Orc3 (Orc1/Cdc6), and Cdc48d (Cdc48/p97 AAA+ ATPase). Overall, we found archaeal MsrA to have opposing MSO reductase and Ubl modifying activities that are associated with oxidative stress responses and controlled by exposure to mild oxidant.« less

Surgical treatment of high-standing greater trochanter.

PubMed

Takata, K; Maniwa, S; Ochi, M

1999-01-01

Eleven patients with high-standing greater trochanter (13 joints) aged 13-36 years underwent surgery. Distal transfer of the greater trochanter (group T) was performed in 4 patients (5 joints) and lateral displacement osteotomy (group L) in 7 (8 joints). The average follow-up duration was 13.4 years in group T and 5.9 years in group L. Clinical results were evaluated by the hip score according to Merle d'Aubigne. The mean hip score in group T was 13.4 points before operation and 15.4 points after operation, and in group L, 12.8 and 17.4 points, respectively. The postoperative clinical results of group L were significantly better than those of group T (P = 0.0494). In radiological evaluation, although the articulo-trochanteric distance (ATD) increased in both groups in group L it improved remarkably from 9.8 to 24.3, indicating a large descending distance of the greater trochanter. The lever arm ratio (LAR) did not change significantly in group T, but it decreased from 1.97 to 1.60 in group L (P = 0.004). This means that the lever arm of the abductors can certainly be extended by lateral displacement osteotomy. Lateral displacement osteotomy is the most effective procedure for high-standing greater trochanter.

Chemical and Thermal Analysis

NASA Technical Reports Server (NTRS)

Bulluck, J. W.; Rushing, R. A.

1997-01-01

Work during the past three years has included significant research in several areas aimed at further clarification of the aging and chemical failure mechanism of thermoplastics (PVDF or Tefzel) for pipes. Among the areas investigated were the crystallinity changes associated with both the Coflon and Tefzel after various simulated environmental exposures using X-Ray diffraction analysis. We have found that significant changes in polymer crystallinity levels occur as a function of the exposures. These crystallinity changes may have important consequences on the fracture, fatigue, tensile, and chemical resistance of the materials. We have also noted changes in the molecular weight distribution and the increased crosslinking of the Coflon material using Gel Permeation Chromatographic Analysis. Again these changes may result in variations in the mechanical and chemical properties in the material. We conducted numerous analytical studies with methods including X-ray Diffraction, Gel Permeation Chromatography, Fourier Transform Infrared Spectroscopy, and Differential Scanning Calorimetry. We investigated a plethora of aged samples of both Tefzel and Coflon that were forwarded from MERL. Pressurized tests were performed on powdered PVDF in a modified Fluid A, which we will call A-2. In this case the ethylene diamine concentration was increased to 3 percent in methanol. Coflon pipe sections and powdered Coflon were exposed in pressure cells at 1700 psi at three separate test temperatures.

Paludiculture on marginal lands - sustainable use of wet peatlands

NASA Astrophysics Data System (ADS)

Oehmke, Claudia; Dahms, Tobias; Wichmann, Sabine; Wichtmann, Wendelin

2017-04-01

Peatlands are marginal lands. If they are drained, they show a short initial productive period. Soil degradation due to peat oxidation leads to numerous problems which increasingly restrict agricultural use and cause significant environmental impacts such as greenhouse gas emissions and eutrophication and thereby produce high external costs. Worldwide greenhouse gas emissions from drained peatlands have a significant share ( 10%) in the emissions from agriculture, forestry and other land use (AFOLU) sectors (Smith et al. 2014). In Germany they contribute more than 35% to the total emissions from agriculture (agricultural sector and cropland and grassland management) (UBA 2016). Rewetting drained peatlands can significantly reduce environmental problems caused by peatland drainage. Continuation of agricultural use with adapted crops and machinery, so called paludiculture (Latin ‚palus' = swamp) stops further degradation, maintains the peat body, reduces climate change mitigation and produces renewable fuels and raw materials. Fen and bog soils are suitable for various different paludicultures. The biomass of Sphagnum (sphagnum farming) cultivated on cut-over bogs or degraded bog grasslands can be used as raw material for horticultural growing media. Flood-tolerant and productive plant species like Common Reed, Reed Canary Grass, Cattail, Black Alder and different Sedge species are suitable for paludiculture on fen soils. Biomass utilization ranges from traditional forms, like fodder production or the use of Common Reed as roof thatch, to new utilization options, that includes biomass use for heat generation, co-subtrates for biorefineries or construction and insulation products. The above-ground biomass of one hectare Common Reed (winter yield=8 t DM) equates to an energy content of 3,000 litre heating oil. A district heating plant (800 kW) in NE Germany demonstrates the feasibility of using biomass from wet fen meadows for local heat generation. Moreover, tests of biomass pellets from paludiculture showed promising results for small (<100KW) and medium scale boilers (<500kW). More examples for paludiculture production and utilization, harvest and logistics, ecosystem services, and economics are described in Wichtmann et al. 2016. Paludiculture is the only sustainable land use concept for marginal peatlands. The implementation of paludiculture on degraded organic soils after rewetting and its biomass use offers renewable biomass sources that have great potential for contributing to the local supply and therewith to the regional added values while preserving organic soils and reducing greenhouse gas emissions. Umweltbundesamt (UBA) (2016) National Inventory Report for the German, Greenhouse Gas Inventory 1990 - 2014, Dessau-Roßlau, 1035 p. Smith, P.; Bustamante ,M.; Ahammad H. et al. (2014) Agriculture, Forestry and Other Land Use (AFOLU). In: Climate Change 2014, Mitigation. Contribution of Working Group III to the Fifth Assessment Report of the Intergovernmental Panel on Climate Change, pp. 799 - 890, Cambridge University Press Cambridge Wichtmann, W.; Joosten, H.; Schröder, C. (2016): Paludiculture, productive use of wet peatlands. Climate protection, biodiversity, regional economic benefits. Schweizerbart Science Publishers, Stuttgart, 272 p.

[Competence based medical education].

PubMed

Bernabó, Jorge G; Buraschi, Jorge; Olcese, Juan; Buraschi, María; Duro, Eduardo

2007-01-01

The strategy of curriculum planning in the majority of the Schools of Medicine has shifted, in the past years, from curriculum models based in contents to outcome oriented curricula. Coincidently the interest in defining and evaluating the clinical competences that a graduate must have has grown. In our country, and particularly in the Associated Hospitals belonging to the Unidad Regional de Enseñanza IV of the UBA School of Medicine, evidence has been gathered showing that the acquisition of clinical competences during the grade is in general insufficient. The foundations and characteristics of PREM (Programa de Requisitos Esenciales Mínimos) are described. PREM is a tool to promote the apprenticeship of abilities and necessary skills for the practice of medicine. The objective of the program is to promote the apprenticeship of a well defined list of core competences considered indispensable for a general practitioner. An outcome oriented curriculum with a clear definition of the expected knowledge, skills and attitudes of a graduate of the programme, the promotion of learning experiences centered in the practice and evaluation tools based in direct observation of the student's performance should contribute to close the gap between what the Medicine Schools traditionally teach and evaluate, and what the doctor needs to know and needs to do to perform correctly its profession.

A quantitative model for oxygen uptake and release in a family of hemeproteins.

PubMed

Bustamante, Juan P; Szretter, María E; Sued, Mariela; Martí, Marcelo A; Estrin, Darío A; Boechi, Leonardo

2016-06-15

Hemeproteins have many diverse functions that largely depend on the rate at which they uptake or release small ligands, like oxygen. These proteins have been extensively studied using either simulations or experiments, albeit only qualitatively and one or two proteins at a time. We present a physical-chemical model, which uses data obtained exclusively from computer simulations, to describe the uptake and release of oxygen in a family of hemeproteins, called truncated hemoglobins (trHbs). Through a rigorous statistical analysis we demonstrate that our model successfully recaptures all the reported experimental oxygen association and dissociation kinetic rate constants, thus allowing us to establish the key factors that determine the rates at which these hemeproteins uptake and release oxygen. We found that internal tunnels as well as the distal site water molecules control ligand uptake, whereas oxygen stabilization by distal site residues controls ligand release. Because these rates largely determine the functions of these hemeproteins, these approaches will also be important tools in characterizing the trHbs members with unknown functions. lboechi@ic.fcen.uba.ar Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Bone Remodeling in Acetabular Reconstruction Using a Kerboull-Type Reinforcement Device and Structural Bone-Grafting in Total Hip Arthroplasty.

PubMed

Oe, Kenichi; Iida, Hirokazu; Tsuda, Kohei; Nakamura, Tomohisa; Okamoto, Naofumi; Ueda, Yusuke

2017-03-01

The purpose of this study was to identify the long-term durability of the Kerboull-type reinforcement device (KT plate) in acetabular reconstruction for massive bone defects, assessing the remodeling of structural bone grafts. This study retrospectively evaluated 106 hips that underwent acetabular reconstruction using a KT plate between November 2000 and December 2010. Thirty-eight primary total hip arthoplasties (THAs) and 68 revised THAs were performed, and the mean duration of clinical follow-up was 8 years (5-14 years). Regarding reconstructing the acetabular bone defects, autografts were used in 37 hips, allografts in 68 hips, and A-W glass ceramics in 2 hips. One hip exhibited radiological migration and no revision for aseptic loosening. The mean Merle d'Aubigné Clinical Score improved from 7.5 points (4-12 points) preoperatively to 10.9 points (9-18 points) at the last follow-up. The Kaplan-Meier survival rate for radiological migration of primary and revised THAs at 10 years was 100% and 97% (95% confidence interval: 96%-100%), respectively. Bone remodeling was evaluated using the radiological demarcation at the bone-to-bone interface, and an improvement of 100% in primary THAs and 94% in revised THAs was observed. For massive bone defects, acetabular reconstruction using the KT plate with a structural bone grafting can yield successful results. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical and Thermal Analysis

NASA Technical Reports Server (NTRS)

Bulluck, J. W.; Rushing, R. A.; Thornton, C. P.

1996-01-01

Work has included significant research in several areas aimed at further clarification of the aging and chemical failure mechanism of thermoplastics (PVDF or Tefzel) for pipes. Among the areas investigated were the crystallinity changes associated with both the Coflon and Tefzel after various simulated environmental exposures using X-Ray diffraction analysis. We have found that significant changes in polymer crystallinity levels occur as a function of the exposures. These crystallinity changes may have important consequences on the fracture, fatigue, tensile, and chemical resistance of the materials. We have also noted changes in the molecular weight distribution of the Coflon material using a dual detector Gel Permeation Analysis. Again these changes may result in variation in the mechanical and chemical properties in the material. We conducted numerous analytical studies with methods including X-Ray Diffraction, Gel Permeation Chromatography, Fourier Transform Infrared Spectroscopy, Thermogravimetric Analysis, and Differential Scanning Calorimetry. We investigated a number of aged samples of both Tefzel and Coflon that were forwarded from MERL. Pressurized tests were performed in a modified Fluid G, which we will call G2. In this case the ethylene diamine concentration was increased to 3 percent in methanol. Coflon pipe sections and powdered Coflon were exposed in pressure cells at 1700 psi at three separate test temperatures, 70 C, 110 C, and 130 C. The primary purpose of the pressure tests in Fluid G2 was to further elucidate the aging mechanism of PVDF degradation.

[Early results of proximal femoral fractures treated with FENIX modular hemiarthroplasty].

PubMed

Görski, Radosław; Górecki, Andrzej; Olszewski, Paweł; Biedrzycki, Jerzy; Skowronek, Paweł

2010-01-01

The article discusses preliminary clinical results in patients with proximal femoral fractures treated with hemiarthroplasty using a FENIX implant. The study group comprised 41 subjects aged 69 to 97 (median age 82.3 year). The follow-up study provided data on 26 subjects (63.4%), among which 15 attended the check-up, 5 subjects refused to visit at the Department and 6 subjects were reported as deceased. Median follow-up period amounted to 6.8 month (1 to 22 months). General hospitalization-related complications occurred in 8 patients (19.5%). During hospitalization no deaths occurred, in the deceased group 3 patients died within 12 months after surgery, while another 3 died after the twelve-month postoperative period (median of 13.3%). According to Merle d'Aubigne-Postel score favorable long-term results were observed in 9 patients (59.9%), 13 patients regained the level of motor function similar to the functional ability prior to fracture. The need to postpone the surgery due to general health status and impaired pre-operative motor function are significant negative prognostic factors. The results obtained were compared with previous efficacy studies on femoral fracture treatment using an Austin-Moore implant. Functional ability and self-reliance was higher in the FENIX group. FENIX arthroplasty effectively helps patients regain self-reliance and motor function thanks to its modular characteristics and anatmoical construction.

Evaluation of powder metallurgy superalloy disk materials

NASA Technical Reports Server (NTRS)

Evans, D. J.

1975-01-01

A program was conducted to develop nickel-base superalloy disk material using prealloyed powder metallurgy techniques. The program included fabrication of test specimens and subscale turbine disks from four different prealloyed powders (NASA-TRW-VIA, AF2-1DA, Mar-M-432 and MERL 80). Based on evaluation of these specimens and disks, two alloys (AF2-1DA and Mar-M-432) were selected for scale-up evaluation. Using fabricating experience gained in the subscale turbine disk effort, test specimens and full scale turbine disks were formed from the selected alloys. These specimens and disks were then subjected to a rigorous test program to evaluate their physical properties and determine their suitability for use in advanced performance turbine engines. A major objective of the program was to develop processes which would yield alloy properties that would be repeatable in producing jet engine disks from the same powder metallurgy alloys. The feasibility of manufacturing full scale gas turbine engine disks by thermomechanical processing of pre-alloyed metal powders was demonstrated. AF2-1DA was shown to possess tensile and creep-rupture properties in excess of those of Astroloy, one of the highest temperature capability disk alloys now in production. It was determined that metallographic evaluation after post-HIP elevated temperature exposure should be used to verify the effectiveness of consolidation of hot isostatically pressed billets.

Spatio-Temporal Constrained Human Trajectory Generation from the PIR Motion Detector Sensor Network Data: A Geometric Algebra Approach

PubMed Central

Yu, Zhaoyuan; Yuan, Linwang; Luo, Wen; Feng, Linyao; Lv, Guonian

2015-01-01

Passive infrared (PIR) motion detectors, which can support long-term continuous observation, are widely used for human motion analysis. Extracting all possible trajectories from the PIR sensor networks is important. Because the PIR sensor does not log location and individual information, none of the existing methods can generate all possible human motion trajectories that satisfy various spatio-temporal constraints from the sensor activation log data. In this paper, a geometric algebra (GA)-based approach is developed to generate all possible human trajectories from the PIR sensor network data. Firstly, the representation of the geographical network, sensor activation response sequences and the human motion are represented as algebraic elements using GA. The human motion status of each sensor activation are labeled using the GA-based trajectory tracking. Then, a matrix multiplication approach is developed to dynamically generate the human trajectories according to the sensor activation log and the spatio-temporal constraints. The method is tested with the MERL motion database. Experiments show that our method can flexibly extract the major statistical pattern of the human motion. Compared with direct statistical analysis and tracklet graph method, our method can effectively extract all possible trajectories of the human motion, which makes it more accurate. Our method is also likely to provides a new way to filter other passive sensor log data in sensor networks. PMID:26729123

THA Using Metal-on-Metal Articulation in Active Patients Younger Than 50 Years

PubMed Central

Bonnomet, François; Clavert, Philippe; Laffargue, Philippe; Migaud, Henri

2008-01-01

The main concern of patients with longer life expectancies and of patients who are younger and more active is the longevity of their total hip arthroplasty. We retrospectively reviewed 83 cementless total hip arthroplasties in 73 patients implanted with metal-on-metal articulation. All patients were younger than 50 years old (average age, 41 years) at the time of the index procedure, and 80% of the patients had an activity level graded 4 or 5 when measured with the system of Devane et al. A 28-mm Metasul articulation was used with three different cementless titanium acetabular components. At the most recent followup (average, 7.3 years), the average Merle d’Aubigné-Postel score improved from a preoperative 11.1 points to 17.4 points. We observed no radiographic evidence of component loosening. Ten acetabular components had lucency limited to one zone. The 10-year survivorship with the end point of revision (ie, exchange of at least one prosthetic or bearing component) was 100% (95% confidence interval, 90%–100%). Metasul bearings with cementless acetabular components remain promising in this high-risk younger patient population. However, additional followup strategies are recommended to determine any possible long-term deleterious effects associated with the dissemination of metallic ions. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18196415

Fresh Osteochondral Allograft Transplantation for Fractures of the Knee.

PubMed

Gracitelli, Guilherme C; Tirico, Luis Eduardo Passarelli; McCauley, Julie C; Pulido, Pamela A; Bugbee, William D

2017-04-01

Objective The purpose of this study was to evaluate functional outcomes and allograft survivorship among patients with knee fracture who underwent fresh osteochondral allograft (OCA) transplantation as a salvage treatment option. Design Retrospective analysis of prospectively collected data. Setting Department of Orthopaedic Surgery at one hospital. Patients Fresh OCAs were implanted for osteochondral lesions after knee fracture in 24 males and 15 females with an average age of 34 years. Twenty-nine lesions (74%) were tibial plateau fractures, 6 (15%) were femoral condyle fractures, and 4 (10%) were patella fractures. Main Outcome Measurements Clinical evaluation included modified Merle d'Aubigné-Postel (18-point), International Knee Documentation Committee, and Knee Society function scores, and patient satisfaction. Failure of OCA was defined as revision OCA or conversion to total knee arthroplasty (TKA). Results Nineteen of 39 knees (49%) had further surgery. Ten knees (26%) were considered OCA failures (3 OCA revisions, 6 TKA, and 1 patellectomy). Survivorship of the OCA was 82.6% at 5 years and 69.6% at 10 years. Among the 29 knees (74%) that had the OCA still in situ, median follow-up was 6.6 years. Pain and function improved from preoperative to latest follow-up; 83% of patients reported satisfaction with OCA results. Conclusion OCA transplantation is a useful salvage treatment option for osteochondral lesions caused by knee fracture. Although the reoperation rate was high, successful outcome was associated with significant clinical improvement.

Developmental Origins of Adult Diseases and Neurotoxicity: Epidemiological and Experimental Studies

PubMed Central

Fox, Donald A.; Grandjean, Philippe; de Groot, Didima; Paule, Merle

2013-01-01

To date, only a small number of commercial chemicals have been tested and documented as developmental neurotoxicants. Moreover, an increasing number of epidemiological, clinical and experimental studies suggest an association between toxicant or drug exposure during the perinatal period and the development of metabolic-related diseases and neurotoxicity later in life. The four speakers in this symposium presented their research results on different neurotoxic chemicals as they relate to the developmental origins of health and adult disease (DOHaD). Philippe Grandjean presented epidemiological data on children exposed to methylmercury and discussed the behavioral outcome measures as they relate to age and stage of brain development. Donald A. Fox presented data that low-to-moderate dose human equivalent gestational lead exposure produced late-onset obesity, and motor and coordination dysfunction only in male mice. Didima de Groot discussed the role of caloric restriction and/or high fat diets during gestation and/or postnatal development in mediating the metabolic and neurotoxic effects of developmental methylmercury exposure in rats. Merle G. Paule addressed the long-term changes in learning, motivation and short-term memory in aged Rhesus monkeys following 24 hour exposure to ketamine during early development. Overall, these presentations addressed fundamental issues in the emerging areas of lifetime neurotoxicity testing, differential vulnerable periods of exposure, nonmonotonic dose-response effects and neurotoxic risk assessment. PMID:22245043

5th Bionanotox and Applications International Research Conference, Peabody, Little Rock, Arkansas, USA

NASA Astrophysics Data System (ADS)

Sabb, Taneicie; Chowdhury, Parimal

2011-06-01

"BioNanoTox and Toxicity: using Technology to Advance Discovery" was this year's theme at the 5th BioNanoTox and Applications International Research Conference held at the Peabody Hotel, Little Rock, Arkansas on November 4-5th, 2010. This year, the international participation in this conference increased to 25 countries spanning the globe. The conference began with opening remarks by Paul Howard, Associate Director of the National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas, United States. Two keynote speakers, Dr. Ananth V. Annapragada and Dr. Merle G. Paule presented lectures on "Toxicity of Novel Nanoparticles for CT imaging" and "The Biology of Neurotoxicity: using Technology to Advance Discovery", respectively. Teachers, students, faculty, and scientists presented oral and poster presentations on fundamental and translational research related to BioNanoTox and related fields of science. Six presentation sessions were held over the two-day conference. There were 31 presentations and 39 posters from disciplines ranging from biology to chemistry, toxicology, nanotechnology, computational sciences, mathematics, engineering, plant science, and biotechnology. Poster presentation awards were presented to three high school students, three high school teachers, and three college students. In addition to poster awards a memorial, travel, and BioNanoTox award were presented. This year's meeting paved the way for a more outstanding meeting for the future.

A Novel Approach for Treatment of Acetabular Fractures

PubMed Central

Xue, Zichao; Qin, Hui; Ding, Haoliang; An, Zhiquan

2016-01-01

Background There is no single approach that provides adequate exposure for treatment of all types of acetabular fractures. We describe our experience with an easier, relatively less invasive pubic symphysis approach (PSA) for the treatment of acetabular fractures. Material/Methods Between March 2011 and March 2012, fifteen patients with acetabular fracture underwent surgery using the PSA technique. Fracture reduction and treatment outcomes were assessed by clinical and radiological examination. Operation time, intraoperative blood loss and postoperative complications were documented. Results Mean operative time was 222±78 minutes. Average blood loss was 993±361 mL. Anatomical reduction was achieved in all patients. Minimum follow-up period was 31 months. Postoperative hypoesthesia in the area of innervation of the lateral femoral cutaneous nerve was reported in one patient, with spontaneous recovery at one month after surgery. No complications were reported during the follow-up period. At the most recent follow up, clinical outcomes were graded as “excellent” in six patients, “good” in eight patients and “fair” in one patient based on the modified Merle d’Aubigné-Postel score. Conclusions PSA appears to be a timesaving and safe approach for treatment of acetabular fractures that affords good visual access and allows for excellent fracture reduction. Our preliminary results revealed a much lower incidence of complications than traditional approaches, suggesting PSA is an alternative for treatment of acetabular fractures. PMID:27734825

Spatio-Temporal Constrained Human Trajectory Generation from the PIR Motion Detector Sensor Network Data: A Geometric Algebra Approach.

PubMed

Yu, Zhaoyuan; Yuan, Linwang; Luo, Wen; Feng, Linyao; Lv, Guonian

2015-12-30

Passive infrared (PIR) motion detectors, which can support long-term continuous observation, are widely used for human motion analysis. Extracting all possible trajectories from the PIR sensor networks is important. Because the PIR sensor does not log location and individual information, none of the existing methods can generate all possible human motion trajectories that satisfy various spatio-temporal constraints from the sensor activation log data. In this paper, a geometric algebra (GA)-based approach is developed to generate all possible human trajectories from the PIR sensor network data. Firstly, the representation of the geographical network, sensor activation response sequences and the human motion are represented as algebraic elements using GA. The human motion status of each sensor activation are labeled using the GA-based trajectory tracking. Then, a matrix multiplication approach is developed to dynamically generate the human trajectories according to the sensor activation log and the spatio-temporal constraints. The method is tested with the MERL motion database. Experiments show that our method can flexibly extract the major statistical pattern of the human motion. Compared with direct statistical analysis and tracklet graph method, our method can effectively extract all possible trajectories of the human motion, which makes it more accurate. Our method is also likely to provides a new way to filter other passive sensor log data in sensor networks.

Reconstruction of the Shallow Acetabulum With a Combination of Autologous Bulk and Impaction Bone Grafting Fixed by Cement.

PubMed

Maruyama, Masaaki; Wakabayashi, Shinji; Ota, Hiroshi; Tensho, Keiji

2017-02-01

Acetabular bone deficiency, especially proximal and lateral deficiency, is a difficult technical problem during primary total hip arthroplasty (THA) in developmental dysplasia of the hip (DDH). We report a new reconstruction method using a medial-reduced cemented socket and additional bulk bone in conjunction with impaction morselized bone grafting (additional bulk bone grafting method). In a population of patients with acetabular dysplasia undergoing THA using a medial-reduced cemented socket and additional bulk bone with impacted morselized bone grafting, we evaluated (1) the radiographic appearance of bone graft; (2) the proportion of cups that developed loosening and subsequent revision; and (3) clinical results (outcome scores and complications). Forty percent of 330 THAs for DDH performed at one center between 1999 and 2009 were defined as shallow dysplastic hips. The additional bulk bone grafting method was performed on 102 THAs with shallow acetabulum (31% for DDH) at one center between 1999 and 2009. We used this approach and technique for shallow acetabuli when a cup protruded from the lateral acetabular edge in preoperative templating. The other 132 dysplastic hips without bone grafting had THA performed at the same periods and served as a control. Acetabuli were defined as shallow when the depth was less than or equal to one-fifth of the pelvic height (cranial-caudal length on radiograph). The additional bulk bone grafting technique was as follows: the resected femoral head was sectioned at 1 to 2 cm thickness, and a suitable size of the bulk bone graft was placed on the lateral iliac cortex and fixed by poly-L-lactate absorbable screws. Autologous impaction morselized bone grafting, with or without hydroxyapatite granules, was performed along with the implantation of a medial-reduced cemented socket. We defined an "incorporated" graft as remodeling and trabeculation including rounding off of the protruding edge of a graft beyond the socket. Radiographic criteria used for determining loosening were migration or a continuous radiolucent zone between the prosthesis/bone cement and host bone. Clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) and the Merle d'Aubigne and Postel score; complications were tallied from chart review. The followup was 10 ± 3 years (range, 6-15 years). One acetabular component (1%) with severe shallow and steep acetabuli showed definite radiographic evidence of loosening and was revised. Clinically, the mean JOA score for the hips treated with additional bulk bone grafting THA in this study improved from 39 ± 10 points preoperatively to 95 ± 5 points postoperatively (p < 0.05, paired t-test). The mean Merle d'Aubigne and Postel score for the hips improved from 7 ± 2 points to 17 ± 1 points (p < 0.05, paired t-test). Complications included a Trendelenburg sign in one hip, dislocation in one, and transient partial sciatic nerve palsy in one. Within 3 years 6 months postoperatively, 101 of 102 additional bulk bone grafting cases showed successful bone remodeling and bone graft reorientation without collapse on radiographs. Partial resorption of the additional bone graft on the lateral side was observed in two hips (2%) with socket abduction angles of < 35°. Achieving stable acetabular fixation is often challenging in the dysplastic hip, especially shallow acetabulum, and a variety of techniques have been described. Early results of combining bulk graft with impaction of morselized graft are promising. Although each surgical technique was well established, further investigation for clinical results of a combination of these techniques might be necessary to confirm longer term outcomes. Level IV, therapeutic study.

Structural model of the hUbA1-UbcH10 quaternary complex: in silico and experimental analysis of the protein-protein interactions between E1, E2 and ubiquitin.

PubMed

Correale, Stefania; de Paola, Ivan; Morgillo, Carmine Marco; Federico, Antonella; Zaccaro, Laura; Pallante, Pierlorenzo; Galeone, Aldo; Fusco, Alfredo; Pedone, Emilia; Luque, F Javier; Catalanotti, Bruno

2014-01-01

UbcH10 is a component of the Ubiquitin Conjugation Enzymes (Ubc; E2) involved in the ubiquitination cascade controlling the cell cycle progression, whereby ubiquitin, activated by E1, is transferred through E2 to the target protein with the involvement of E3 enzymes. In this work we propose the first three dimensional model of the tetrameric complex formed by the human UbA1 (E1), two ubiquitin molecules and UbcH10 (E2), leading to the transthiolation reaction. The 3D model was built up by using an experimentally guided incremental docking strategy that combined homology modeling, protein-protein docking and refinement by means of molecular dynamics simulations. The structural features of the in silico model allowed us to identify the regions that mediate the recognition between the interacting proteins, revealing the active role of the ubiquitin crosslinked to E1 in the complex formation. Finally, the role of these regions involved in the E1-E2 binding was validated by designing short peptides that specifically interfere with the binding of UbcH10, thus supporting the reliability of the proposed model and representing valuable scaffolds for the design of peptidomimetic compounds that can bind selectively to Ubcs and inhibit the ubiquitylation process in pathological disorders.

The Saccharomyces cerevisiae LOS1 gene involved in pre-tRNA splicing encodes a nuclear protein that behaves as a component of the nuclear matrix.

PubMed

Shen, W C; Selvakumar, D; Stanford, D R; Hopper, A K

1993-09-15

Mutations of the Saccharomyces cerevisiae LOS1 gene cause the accumulation of end matured intron-containing pre-tRNAs at elevated temperatures. In an effort to decipher the role of the LOS1 protein in pre-tRNA splicing, we have analyzed the LOS1 gene and its protein product. The LOS1 gene is located on the left arm of chromosome XI and the order of genes in this area of the chromosome is .... URA1 ... SAC1 TRP3 UBA1 STE6 LOS1 .... FAS1..... The LOS1 open reading frame encodes a putative protein of 1100 amino acids that shows no significant homology to other genes. The LOS1 open reading frame was tagged with the influenza virus hemagglutinin epitope recognized by the 12CA5 antibody. The 12CA5 antibody recognizes an epitope-tagged protein of the size predicted by the LOS1 open reading frame. Using this antibody for indirect immunofluorescence and cell fractionation studies we show that the LOS1 protein is located in nuclei. Los1p cannot be extracted from nuclei by treatment with nucleases, salts, or Triton X-100. This insolubility suggests that Los1p is a component of the nucleoskeleton. We propose that LOS1 mutations may affect pre-tRNA processing via alteration of the nuclear matrix.

Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.

PubMed

Harripaul, R; Vasli, N; Mikhailov, A; Rafiq, M A; Mittal, K; Windpassinger, C; Sheikh, T I; Noor, A; Mahmood, H; Downey, S; Johnson, M; Vleuten, K; Bell, L; Ilyas, M; Khan, F S; Khan, V; Moradi, M; Ayaz, M; Naeem, F; Heidari, A; Ahmed, I; Ghadami, S; Agha, Z; Zeinali, S; Qamar, R; Mozhdehipanah, H; John, P; Mir, A; Ansar, M; French, L; Ayub, M; Vincent, J B

2018-04-01

Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7 and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.

KCNN4 and S100A14 act as predictors of recurrence in optimally debulked patients with serous ovarian cancer

PubMed Central

Hu, Ting; Sun, Qian; Wu, Jianli; Lin, Xingguang; Luo, Danfeng; Sun, Chaoyang; Wang, Changyu; Zhou, Bo; Li, Na; Xia, Meng; Lu, Hao; Meng, Li; Xu, Xiaoyan; Hu, Junbo; Ma, Ding; Chen, Gang; Zhu, Tao

2016-01-01

Approximately 50-75% of patients with serous ovarian carcinoma (SOC) experience recurrence within 18 months after first-line treatment. Current clinical indicators are inadequate for predicting the risk of recurrence. In this study, we used 7 publicly available microarray datasets to identify gene signatures related to recurrence in optimally debulked SOC patients, and validated their expressions in an independent clinic cohort of 127 patients using immunohistochemistry (IHC). We identified a two-gene signature including KCNN4 and S100A14 which was related to recurrence in optimally debulked SOC patients. Their mRNA expression levels were positively correlated and regulated by DNA copy number alterations (CNA) (KCNN4: p=1.918e-05) and DNA promotermethylation (KCNN4: p=0.0179; S100A14: p=2.787e-13). Recurrence prediction models built in the TCGA dataset based on KCNN4 and S100A14 individually and in combination showed good prediction performance in the other 6 datasets (AUC:0.5442-0.9524). The independent cohort supported the expression difference between SOC recurrences. Also, a KCNN4 and S100A14-centered protein interaction subnetwork was built from the STRING database, and the shortest regulation path between them, called the KCNN4-UBA52-KLF4-S100A14 axis, was identified. This discovery might facilitate individualized treatment of SOC. PMID:27270322

International Research Project on the Effects of Chemical Ageing of Polymers on Performance Properties: Chemical and Thermal Analysis

NASA Technical Reports Server (NTRS)

Bulluck, J. W.; Rushing, R. A.

1996-01-01

Work during the past six months has included significant research in several areas aimed at further clarification of the aging and chemical failure mechanism of thermoplastics (PVDF or Tefzel) pipes. Among the areas investigated were the crystallinity changes associated with both the Coflon and Tefzel after various simulated environmental exposures using X-ray diffraction analysis. We have found that significant changes in polymer crystallinity levels occur as a function of the exposures. These crystallinity changes may have important consequences on the fracture, fatigue, tensile, and chemical resistance of the materials. We have also noted small changes in the molecular weight distribution. Again these changes may result in variations in the mechanical and chemical properties in the material. We conducted numerous analytical studies with methods including X-ray Diffraction, Gel Permeation Chromatography, Fourier Transform Infrared Spectroscopy, Ultra- Violet Scanning Analysis, GC/Mass Spectrometry, Differential Scanning Calorimetry and Thermomechanical Analysis. In the ultra-violet analysis we noted the presence of an absorption band indicative of triene formation. We investigated a number of aged samples of both Tefzel and Coflon that were forwarded from MERL. We also cast films at SWT and subjected these films to a refluxing methanol 1% ethylene diamine solution. An updated literature search was conducted using Dialog and DROLLS to identify any new papers that may have been published in the open literature since the start of this project. The updated literature search and abstracts are contained in the Appendix section of this report.

Proximal Femoral Reconstructions with Bone Impaction Grafting and Metal Mesh

PubMed Central

Comba, Fernando; Piccaluga, Francisco

2009-01-01

Extensive circumferential proximal cortical bone loss is considered by some a contraindication for impaction bone grafting in the femur. We asked whether reconstruction with a circumferential metal mesh, impacted bone allografts, and a cemented stem would lead to acceptable survival in these patients. We retrospectively reviewed 14 patients (15 hips) with severe proximal femoral bone defects (average, 12 cm long; 14 type IV and one type IIIB using the classification of Della Valle and Paprosky) reconstructed with this method. The minimum followup was 20 months (average, 43.2 months; range, 20–72 months). Preoperative Merle D’Aubigné and Postel score averaged 4.8 points. With revision of the stem as the end point, the survivorship of the implant was 100% at one year and 86.6% at 72 months. The mean functional score at last followup was 14.4 points. We observed two fractures of the metal mesh at 31 and 48 months in cases reconstructed with a stem that did not bypass the mesh. Dislocation (3 cases) and acute deep infection (3 cases) were the most frequent complications. Patients with complete absence of the proximal femur may be candidates for biological proximal femoral reconstructions using this salvage procedure. Bone impaction grafting must be a routine technique if this method is selected. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:19294476

Vulnerability and adaptation to water scarcity in the European Alps

NASA Astrophysics Data System (ADS)

Isoard, S.; McCallum, S.; Prutsch, A.; Benno Hain, B.; Schauser, I.

2009-04-01

The European Environment Agency (EEA) has recently undertaken a project addressing vulnerability and adaptation to water availability in the European Alps. Mountains are indeed one of the most vulnerable regions to climate change in Europe (EEA 2008, IPCC 2007).The Alps, in particular, can be presented as the ‘water towers' of Europe (the amount of water delivered by the Alps allocates 40% of EU consumption) where changes in water availability affect all socio-economical sectors. This therefore makes adaptation actions a regional topic with an outstanding European dimension. The specific objectives of the study were to highlight the importance of the Alps in their function as ‘water towers' for Europe and analyse the vulnerability of the Alpine Region with regard to impacts of climate change (but also to global change as a whole) focussing on water availability. Given the EU and regional policy background with regard to adaptation and water issues, the study assessed the possible needs, constraints and opportunities for adaptation to the adverse impacts for various sectors pending on water resources. Findings of this activity expanded the knowledge base, fed into the preparation of European Commission's 2009 White Paper and the Alpine Convention 2009 Report on the State of the Alps, and complemented other recent studies (e.g. OECD 2007, European Parliament Committee on Agriculture & Rural Development 2008). The method used for the study relied on the one hand on findings from recent key publications on climate change impacts (EEA 2008, IPCC 2007) and EU research projects (e.g. ClimChAlp, ProClim); on the other side it was based on selected case studies chosen within the four climatic regions of the eight Alpine countries for which an extensive series of interviews with local and regional stakeholders and decision makers has been undertaken. The interviewees had been directly involved in designing and implementing water availability-related adaptation measures relating to the respective case studies. The analysis of the case studies highlighted key drivers of adaptation measures, the multi-level governance surrounding this type of policy actions, success factors and barriers (e.g. lack of knowledge, governance shortcomings, coordination issues, spatial and temporal distribution, and competition for resources) that prevent more extensive adaptation actions. Examples of good practices were given as well as further adaptation needs in view of future climate change. Since the study relied mainly on stakeholders' interviews, the major focus lies on building local/regional adaptive capacity that effectively supports adaptation as a social and institutional process. It also provided a synthesis of key vulnerabilities and adaptation options across Europe/Alpine river catchments and recommendations on how to transfer experiences and knowledge in practical implementation of adaptation measures, in particular to other mountain regions (e.g. Carpathian). In this context the study supports regional and local administrations in making informed decisions to better develop and implement adaptation strategies. This EEA study was conducted by the European Topic Centre on Air and Climate Change (UBA Germany, UBA Austria, Potsdam Institute for Climate Impact Research) in cooperation with the Permanent Secretariat of the Alpine Convention (Innsbruck), the European Academy (Bolzano) and the Environment Protection Agency of Slovenia. The study will be published in the first half of 2009 as an EEA Technical Report and will be actively disseminated to stakeholders and decision-makers in the Alpine region through best suited events in collaboration with the Alpine Convention.

Health related guide values for drinking-water since 1993 as guidance to assess presence of new analytes in drinking-water.

PubMed

Dieter, Hermann H

2014-03-01

Regulatory toxicologists, when going into assessment of a new analyte in drinking-water, very often miss the occasion to revert to scientifically consensual virtually safe lifetime exposure reference doses and corresponding health-related guide values (HRGV) for drinking-water, be those derived either to avoid concern over "threshold effects" or concern over exceedance of an unacceptable non-threshold cancer risk level. They then need a more restrictive precautionary yet science-compatible approach to directly avoid concern over the presence (measured concentration) of a new analyte in drinking-water. Therefore, the German Environment Agency (UBA, Umweltbundesamt) decided in 2003 to extrapolate international toxicological expertise collected since 1993 from assessing "old" analytes in drinking-water on new ones in form of five HRIV=health related indication values. They indicate the reasonable lowest maximal concentration from which on tiered or stepwise human toxicological evaluation of a new analyte might be necessary and meaningful. Their regulatory-toxicological function is that of placeholders as long as a possibly higher scientific HRGV or a surrogate value based on a threshold of toxicological concern (TTC) was not broadly agreed by science. The five-step HRIV scale between 0.01 and 3.0 μg/l combines international toxicological experience gained from "old" analytes since 1993 with the concepts of safety factors (SF(D)) to assess database deficiency and science-related extrapolation factors (EF) to extrapolate experimental data on humans. Each HRIV is valid and safe for a 2 l/day drinking-water exposure scenario either counting for 10% relative source contribution (compounds with threshold effects) or for a lifetime non-threshold cancer risk of up to 10(-6) and is the higher the more positive information exists regarding possible effects at critical toxic endpoints and for length of possible exposure. Past (historical) and present evaluations of "old" analytes were available in form of hundreds of HRGVs to count in 2 liters per day and person for 10% RSC or a 10(-6) non-threshold risk. These HRGVs were calculated by the present author either from ADI-, TDI- or RfD-values derived since 1993 by six large health authorities or they were identified directly at their websites or in the literature, always looking for confirmed or assumed worldwide relevance for drinking-water (resources). 36 of these up to 200 "old" analytes were ascribed since 1993 at least once an HRGV at or below 1 μg/l for (confirmed or provisionally assumed) "high" or "very high" threshold chronic toxicity. None but one of the corresponding 113 scientific HRGVs fell distinctly short of 0.3 μg/l. Only 14 carcinogens turned out as being relevant for drinking-water due to confirmed occurrence and coincident toxicological significance there. 13 of these exhibited a structural alert for genotoxicity. Ten of these 13 were "high-potency" genotoxic carcinogens with presently calculated non-threshold 10(-6) risk minimal HRGVs between 0.06 μg/l and 0.005 μg/l (9 compounds) or possibly down to 0.0007 μg/l (1 compound). This motivated UBA to propose a precautionary range between a minimal HRIV0=0.01 and a HRIV1=0.1 μg/l to assess new analytes bearing a structural alert for genotoxicity. The HRGVs for the remaining three (from 13) carcinogens with alerts for genotoxicity were at best similar for both genotoxic and non-genotoxic effects and higher or equal to 0.3 μg/l. Therefore, a minimal HRIV of 0.01 μg/l (HRIV0) or even 0.1 μg/l (HRIV1) would have appeared too low for assessing the presence in drinking-water of new analytes with no other human toxicity data than proven absence of both genotoxicity and of structural alerts for such. Instead, UBA proposes to provisionally assess such compounds by its next higher precautionary of HRIV3=0.3 μg/l. Any value once set is open for falsification upwards to either 1.0 μg/l (HRIV4) or 3.0 μg/l (HRIV5) or even for being replaced by an HRGV>3.0 μg/l if pertinent high toxicity effect potentials different from genotoxicity are similarly ruled out by either mechanistic and TTC-based arguments or a tiered experimental (in vitro and/or in vivo) approach. Regulatory-toxicological expertise gained since 1993 with "old" analytes in drinking-water (resources) and its extrapolation by analogy on new analytes with patchy human toxicological database allows for provisional assessment of their presence in drinking-water in form of five precautionary HRIVs. Selecting a HRIV, instead referring to a TTC or a virtually safe reference dose, just asks an expert judgment on the degree of formal completeness and informational potential of a new analyte's human toxicity database. Exceedance of a HRIV indicates need for supplementary toxicological data to improve assessment, their nature and comprehensiveness depending on degree and expected length of exceedance. The regulatory function of a HRIV is that of a placeholder for a possibly higher TTC-based surrogate HRGVTTC or a highest possible science-based HRGV. Copyright © 2013 Elsevier GmbH. All rights reserved.

Reduction of Line Edge Roughness of Polystyrene-block-Poly(methyl methacrylate) Copolymer Nanopatterns By Introducing Hydrogen Bonding at the Junction Point of Two Block Chains.

PubMed

Lee, Kyu Seong; Lee, Jaeyong; Kwak, Jongheon; Moon, Hong Chul; Kim, Jin Kon

2017-09-20

To apply well-defined block copolymer nanopatterns to next-generation lithography or high-density storage devices, small line edge roughness (LER) of nanopatterns should be realized. Although polystyrene-block-poly(methyl methacrylate) copolymer (PS-b-PMMA) has been widely used to fabricate nanopatterns because of easy perpendicular orientation of the block copolymer nanodomains and effective removal of PMMA block by dry etching, the fabricated nanopatterns show poorer line edge roughness (LER) due to relatively small Flory-Huggins interaction parameter (χ) between PS and PMMA chains. Here, we synthesized PS-b-PMMA with urea (U) and N-(4-aminomethyl-benzyl)-4-hydroxymethyl-benzamide (BA) moieties at junction of PS and PMMA chains (PS-U-BA-PMMA) to improve the LER. The U-BA moieties serves as favorable interaction (hydrogen bonding) sites. The LER of PS line patterns obtained from PS-U-BA-PMMA was reduced ∼25% compared with that obtained from neat PS-b-PMMA without BA and U moieties. This is attributed to narrower interfacial width induced by hydrogen bonding between two blocks, which is confirmed by small-angle X-ray scattering. This result implies that the introduction of hydrogen bonding into block copolymer interfaces offers an opportunity to fabricate well-defined nanopatterns with improved LER by block copolymer self-assembly, which could be a promising alternative to next-generation extreme ultraviolet lithography.

Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway.

PubMed

Liu, Kuang-Kai; Qiu, Wei-Ru; Naveen Raj, Emmanuel; Liu, Huei-Fang; Huang, Hou-Syun; Lin, Yu-Wei; Chang, Chien-Jen; Chen, Ting-Hua; Chen, Chinpiao; Chang, Huan-Cheng; Hwang, Jenn-Kang; Chao, Jui-I

2017-01-02

Selective macroautophagy/autophagy plays a pivotal role in the processing of foreign pathogens and cellular components to maintain homeostasis in human cells. To date, numerous studies have demonstrated the uptake of nanoparticles by cells, but their intracellular processing through selective autophagy remains unclear. Here we show that carbon-based nanodiamonds (NDs) coated with ubiquitin (Ub) bind to autophagy receptors (SQSTM1 [sequestosome 1], OPTN [optineurin], and CALCOCO2/NDP52 [calcium binding and coiled-coil domain 2]) and are then linked to MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) for entry into the selective autophagy pathway. NDs are ultimately delivered to lysosomes. Ectopically expressed SQSTM1-green fluorescence protein (GFP) could bind to the Ub-coated NDs. By contrast, the Ub-associated domain mutant of SQSTM1 (ΔUBA)-GFP did not bind to the Ub-coated NDs. Chloroquine, an autophagy inhibitor, prevented the ND-containing autophagosomes from fusing with lysosomes. Furthermore, autophagy receptors OPTN and CALCOCO2/NDP52, involved in the processing of bacteria, were found to be involved in the selective autophagy of NDs. However, ND particles located in the lysosomes of cells did not induce mitotic blockage, senescence, or cell death. Single ND clusters in the lysosomes of cells were observed in the xenografted human lung tumors of nude mice. This study demonstrated for the first time that Ub-coated nanoparticles bind to autophagy receptors for entry into the selective autophagy pathway, facilitating their delivery to lysosomes.

Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells

PubMed Central

Zhang, Y-B; Gong, J-L; Xing, T-Y; Zheng, S-P; Ding, W

2013-01-01

HAMLET is a complex of oleic acids and decalcified α-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death. PMID:23519119

Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells.

PubMed

Zhang, Y-B; Gong, J-L; Xing, T-Y; Zheng, S-P; Ding, W

2013-03-21

HAMLET is a complex of oleic acids and decalcified α-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death.

Position paper for health authorities: archived clinical pathology data-treasure to revalue and appropriate.

PubMed

Nwose, E U; Richards, R S; Butkowski, E; Cann, Nathan

2010-12-01

Archived clinical pathology data (ACPD) is recognized as useful for research. Given our privileged de-identified ACPD from South West Pathology Service (SWPS), attempt is made to estimate what it would cost any researcher without such privilege to generate the same data. The Ethics Committee of the Area Health Service approved a request for Dr. Uba Nwose to use de-identified ACPD acquired by the SWPS for clinical laboratory-based translational biomedical science research. 10-years (1999-2008) have been pooled to constitute the database. Data include blood sugar, cholesterol, D-dime, ESR, glucose tolerance, haematocrit, HbA 1 c, homocysteine, serum creatinine, total protein and vitamins [C & E] amongst others. For this report, the bulk-billed-cost of tests were estimated based on number and unit price of each test performed. AU$ 17,507,136.85 is the cost paid by Medicare in the period. This amount is a conservative estimate that could be spent to generate such 10-years data in the absence of ACPD. The health/pathology service has not given any financial research grant. However, the support-in-kind is worth more than celebrated competitive research grants. It calls for revaluatrion by academic, research and scientific institutions the use ofACPD. For the countries where such provision is non-existent, this report provides a 'Position Paper' to present to the directorates or institutes of health authorities to appropriate the value of ACPD and approve of their use as a research treasure and resource management tool.

Developing a list of reference chemicals for testing alternatives to whole fish toxicity tests.

PubMed

Schirmer, Kristin; Tanneberger, Katrin; Kramer, Nynke I; Völker, Doris; Scholz, Stefan; Hafner, Christoph; Lee, Lucy E J; Bols, Niels C; Hermens, Joop L M

2008-11-11

This paper details the derivation of a list of 60 reference chemicals for the development of alternatives to animal testing in ecotoxicology with a particular focus on fish. The chemicals were selected as a prerequisite to gather mechanistic information on the performance of alternative testing systems, namely vertebrate cell lines and fish embryos, in comparison to the fish acute lethality test. To avoid the need for additional experiments with fish, the U.S. EPA fathead minnow database was consulted as reference for whole organism responses. This database was compared to the Halle Registry of Cytotoxicity and a collation of data by the German EPA (UBA) on acute toxicity data derived from zebrafish embryos. Chemicals that were present in the fathead minnow database and in at least one of the other two databases were subject to selection. Criteria included the coverage of a wide range of toxicity and physico-chemical parameters as well as the determination of outliers of the in vivo/in vitro correlations. While the reference list of chemicals now guides our research for improving cell line and fish embryo assays to make them widely applicable, the list could be of benefit to search for alternatives in ecotoxicology in general. One example would be the use of this list to validate structure-activity prediction models, which in turn would benefit from a continuous extension of this list with regard to physico-chemical and toxicological data.

The role of triple pelvic osteotomy in therapy of residual hip dysplasia and sequel of AVN: long-term experience.

PubMed

Dungl, P; Rejholec, M; Chomiak, J; Grill, F

2007-01-01

Triple pelvic osteotomy was performed for sequel of DDH including AVN between 1981 and 2002 for 329 patients (351 hips, 280 females, 49 males, average age at surgery 16.5 years, range 9-41 years, follow-up 4-25 years). A small modification of Steel's technique consisting of strictly subperiostal resection of segment from both pubic and ischial bone was used. Average gain of lengthening extremity was 1.8 cm. The average CE angle was improved from 7.8 to 35.5 degrees. Clinical results were evaluated according to Merle d'Aubigne and reflected to the preoperative clinical and radiological findings. There were 146 hip joints in 128 patients (76%) with excellent results in the group of congruent hips without arthrosis. In 182 hips in 178 patients with hip joints with some deformity, limited ROM and decentration, 40% were excellent, 32% good, 23% fair and 5% unsatisfactory results were achieved. The group of decentrated hip joints in young adults in incongruency, limited ROM and sometimes severe arthrosis consisted of 23 monolateral surgeries with 39% unsatisfactory, 39% fair and 22% good results, respectively. No major neurovascular complications were seen. Non-unions were recorded in 19 patients (5.4%), including 2 triple and 2 double non-unions. Based on our long-term experience, we can conclude that triple pelvic osteotomy according to Steel in our modification is a safe method and gives regularly excellent or good results for correction of clinical and radiographic appearance of acetabular dysplasia when there is a proper indication.

Climatic potential for tourism in the Black Forest, Germany — winter season

NASA Astrophysics Data System (ADS)

Endler, Christina; Matzarakis, Andreas

2011-05-01

Climate change, whether natural or human-caused, will have an impact on human life, including recreation and tourism among other things. In this study, methods from biometeorology and tourism climatology are used to assess the effect of a changed climate on tourism and recreation in particular. The study area is the Black Forest mountainous region of south-west Germany, which is well known for its tourist and recreational assets. Climate model projections for the 2021-2050 period based on REMO-UBA simulations with a high spatial resolution of 10 km are compared to a 30-year reference period (1971-2000) using the IPCC emission scenarios A1B and B1. The results show that the mean winter air temperature will increase by up to 1.8°C, which is the most pronounced warming compared to the other seasons. The annual precipitation amount will increase marginally by 5% in the A1B scenario and 10% in the B1 scenario. Winter precipitation contributes about 10% (A1B) and 30% (B1) to variations in annual precipitation. Although the results show that winter precipitation will increase slightly, snow days affecting skiing will be reduced on average by approximately 40% due to regional warming. Cold stress will be reduced on average by up to 25%. The result is that the thermal environment will be advanced, and warmer winters are likely to lead to an upward altitudinal shift of ski resorts and winter sport activities, thus displacing land-use currently dedicated to nature conservation.

Network analysis of ChIP-Seq data reveals key genes in prostate cancer.

PubMed

Zhang, Yu; Huang, Zhen; Zhu, Zhiqiang; Liu, Jianwei; Zheng, Xin; Zhang, Yuhai

2014-09-03

Prostate cancer (PC) is the second most common cancer among men in the United States, and it imposes a considerable threat to human health. A deep understanding of its underlying molecular mechanisms is the premise for developing effective targeted therapies. Recently, deep transcriptional sequencing has been used as an effective genomic assay to obtain insights into diseases and may be helpful in the study of PC. In present study, ChIP-Seq data for PC and normal samples were compared, and differential peaks identified, based upon fold changes (with P-values calculated with t-tests). Annotations of these peaks were performed. Protein-protein interaction (PPI) network analysis was performed with BioGRID and constructed with Cytoscape, following which the highly connected genes were screened. We obtained a total of 5,570 differential peaks, including 3,726 differentially enriched peaks in tumor samples and 1,844 differentially enriched peaks in normal samples. There were eight significant regions of the peaks. The intergenic region possessed the highest score (51%), followed by intronic (31%) and exonic (11%) regions. The analysis revealed the top 35 highly connected genes, which comprised 33 differential genes (such as YWHAQ, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein and θ polypeptide) from ChIP-Seq data and 2 differential genes retrieved from the PPI network: UBA52 (ubiquitin A-52 residue ribosomal protein fusion product (1) and SUMO2 (SMT3 suppressor of mif two 3 homolog (2) . Our findings regarding potential PC-related genes increase the understanding of PC and provides direction for future research.

Selection and evaluation of novel reference genes for quantitative reverse transcription PCR (qRT-PCR) based on genome and transcriptome data in Brassica napus L.

PubMed

Yang, Hongli; Liu, Jing; Huang, Shunmou; Guo, Tingting; Deng, Linbin; Hua, Wei

2014-03-15

Selection of reference genes in Brassica napus, a tetraploid (4×) species, is a very difficult task without information on genome and transcriptome. By now, only several traditional reference genes which show significant expression differentiation under different conditions are used in B. napus. In the present study, based on genome and transcriptome data of the rapeseed Zhongshuang-11 cultivar, 14 candidate reference genes were screened for investigation in different tissues, cultivars, and treated conditions of B. napus. These genes were as follows: ELF5, ENTH, F-BOX7, F-BOX2, FYPP1, GDI1, GYF, MCP2d, OTP80, PPR, SPOC, Unknown1, Unknown2 and UBA. Among them, excluding GYF and FYPP1, another 12 genes, were identified to perform better than traditional reference genes ACTIN7 and GAPDH. To further validate the accuracy of the newly developed reference genes in normalization, expression levels of BnCAT1 (B. napus catalase 1) in different rapeseed tissues and seedlings under stress conditions were normalized by the three most stable reference genes PPR, GDI1, and ENTH and little difference existed in normalization results. To the best of our knowledge, this is the first time B. napus reference genes have been provided with the help of complete genome and transcriptome information. The new reference genes provided in this study are more accurate than previously reported reference genes in quantifying expression levels of B. napus genes. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Novel candidate genes of the PARK7 interactome as mediators of apoptosis and acetylation in multiple sclerosis: An in silico analysis.

PubMed

Vavougios, George D; Zarogiannis, Sotirios G; Krogfelt, Karen Angeliki; Gourgoulianis, Konstantinos; Mitsikostas, Dimos Dimitrios; Hadjigeorgiou, Georgios

2018-01-01

currently only 4 studies have explored the potential role of PARK7's dysregulation in MS pathophysiology Currently, no study has evaluated the potential role of the PARK7 interactome in MS. The aim of our study was to assess the differential expression of PARK7 mRNA in peripheral blood mononuclears (PBMCs) donated from MS versus healthy patients using data mining techniques. The PARK7 interactome data from the GDS3920 profile were scrutinized for differentially expressed genes (DEGs); Gene Enrichment Analysis (GEA) was used to detect significantly enriched biological functions. 27 differentially expressed genes in the MS dataset were detected; 12 of these (NDUFA4, UBA2, TDP2, NPM1, NDUFS3, SUMO1, PIAS2, KIAA0101, RBBP4, NONO, RBBP7 AND HSPA4) are reported for the first time in MS. Stepwise Linear Discriminant Function Analysis constructed a predictive model (Wilk's λ = 0.176, χ 2 = 45.204, p = 1.5275e -10 ) with 2 variables (TIDP2, RBBP4) that achieved 96.6% accuracy when discriminating between patients and controls. Gene Enrichment Analysis revealed that induction and regulation of programmed / intrinsic cell death represented the most salient Gene Ontology annotations. Cross-validation on systemic lupus erythematosus and ischemic stroke datasets revealed that these functions are unique to the MS dataset. Based on our results, novel potential target genes are revealed; these differentially expressed genes regulate epigenetic and apoptotic pathways that may further elucidate underlying mechanisms of autorreactivity in MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Creation of a High-Resolution Product CLC2006_BACKDATING by a Backward Look from the Digital Land Cover Model DLM-DE2009 to 2006 - a Contribution to the German Corine Land Cover 2012 Project Within a Bottom-Up Approach

NASA Astrophysics Data System (ADS)

Keil, M.; Esch, T.; Feigenspan, S.; Marconcini, M.; Metz, A.; Ottinger, M.; Zeidler, J.

2015-04-01

For the update 2012 of CORINE Land Cover, in Germany a new approach has been developed in order to profit from the higher accuracies of the national topographic database. In agreement between the Federal Environment Agency (UBA) and the Federal Agency for Cartography and Geodesy (BKG), CLC2012 has been derived from an updated digital landscape model DLM-DE, which is based on the Official Topographical Cartographic Information System ATKIS of the land survey authorities. The DLM-DE 2009 created by the BKG served as the base for the update 2012 in the national and EU context, both under the responsibility of the BKG. In addition to the updated CLC2012, a second product, the layer "CLC_Change" (2006-2012) was also requested by the European Environment Agency. The objective of the project part of DLR-DFD was to contribute the primary change areas from 2006 to 2009 in the phase of method change using the refined 2009 geometry of the DLM-DE 2009 for a retrospective view back to 2006. A semiautomatic approach was developed for this task, with an important role of AWiFS time series data of 2005 / 2006 in the context of separation between grassland - arable land. Other valuable datasets for the project were already available GMES land monitoring products of 2006 like the soil sealing layer 2006. The paper describes the developed method and discusses exemplary results of the CORINE backdating project part.

Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway

PubMed Central

Liu, Kuang-Kai; Qiu, Wei-Ru; Naveen Raj, Emmanuel; Liu, Huei-Fang; Huang, Hou-Syun; Lin, Yu-Wei; Chang, Chien-Jen; Chen, Ting-Hua; Chen, Chinpiao; Chang, Huan-Cheng; Hwang, Jenn-Kang; Chao, Jui-I

2017-01-01

ABSTRACT Selective macroautophagy/autophagy plays a pivotal role in the processing of foreign pathogens and cellular components to maintain homeostasis in human cells. To date, numerous studies have demonstrated the uptake of nanoparticles by cells, but their intracellular processing through selective autophagy remains unclear. Here we show that carbon-based nanodiamonds (NDs) coated with ubiquitin (Ub) bind to autophagy receptors (SQSTM1 [sequestosome 1], OPTN [optineurin], and CALCOCO2/NDP52 [calcium binding and coiled-coil domain 2]) and are then linked to MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) for entry into the selective autophagy pathway. NDs are ultimately delivered to lysosomes. Ectopically expressed SQSTM1-green fluorescence protein (GFP) could bind to the Ub-coated NDs. By contrast, the Ub-associated domain mutant of SQSTM1 (ΔUBA)-GFP did not bind to the Ub-coated NDs. Chloroquine, an autophagy inhibitor, prevented the ND-containing autophagosomes from fusing with lysosomes. Furthermore, autophagy receptors OPTN and CALCOCO2/NDP52, involved in the processing of bacteria, were found to be involved in the selective autophagy of NDs. However, ND particles located in the lysosomes of cells did not induce mitotic blockage, senescence, or cell death. Single ND clusters in the lysosomes of cells were observed in the xenografted human lung tumors of nude mice. This study demonstrated for the first time that Ub-coated nanoparticles bind to autophagy receptors for entry into the selective autophagy pathway, facilitating their delivery to lysosomes. PMID:27846374

Human biomonitoring: Science and policy for a healthy future, April 17-19, 2016, Berlin, Germany.

PubMed

Joas, Anke; Schwedler, Gerda; Choi, Judy; Kolossa-Gehring, Marike

2017-03-01

Following the success of the 1st International Conference on Human Biomonitoring (HBM) in Berlin in 2010, the 2nd International Conference on Human Biomonitoring took place in Berlin from April 17-19, 2016 for an exchange and updates among participants on all aspects relating to HBM. Entitled "Science and Policy for a Healthy Future", the conference brought together international experts from the scientific sector, politics, authorities, industry, non-governmental organizations (NGOs), and other involved associations. The conference took a critical look at today's chemicals that have a potential impact on human health and should be investigated as a matter of priority. It also discussed current activities and research efforts on HBM occurring worldwide, presented HBM success stories, and emphasized areas, where further research and focus are needed to improve the use of HBM for policy making. In many countries, HBM has been proven to be a useful tool and warning system to indicate problematic human exposure to pollutants and to evaluate the effectiveness of existing chemicals policy and regulations. However, important challenges remain such as exposure assessment of mixtures of chemicals, the development of analytical methods to detect new chemicals of concern (e.g., substitutes for phthalates), the identification of exposure sources, and the assessment of the impact of exposure on health. This brief report summarizes the discussions and contributions from this conference, which was jointly organized by the German Federal Environment Agency (UBA) and the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMUB). Copyright © 2017.

Impact of community-based vector control on house infestation and Trypanosoma cruzi infection in Triatoma infestans, dogs and cats in the Argentine Chaco.

PubMed

Cardinal, M V; Lauricella, M A; Marcet, P L; Orozco, M M; Kitron, U; Gürtler, R E

2007-09-01

The relative impact of two community-based vector control strategies on house infestation by Triatoma infestans and Trypanosoma cruzi infection in bugs, domestic dogs and cats was assessed in two neighboring rural areas comprising 40 small villages and 323 houses in one of the regions most endemic for Chagas disease in northern Argentina. The prevalence and abundance of domestic infestation were 1.5- and 6.5-fold higher, respectively, in the area under pulsed, non-supervised control actions operating under the guidelines of the National Vector Control Program (NCVP) than in the area under sustained, supervised surveillance carried out jointly by the UBA research team and NCVP. The prevalence of infestation and infection varied widely among village groups within each area. In the pulsed control area, the prevalence of infection in bugs, dogs and cats was two- to three-fold higher than in the area under sustained surveillance, most of the infected animals qualified as autochthonous cases, and evidence of recent transmission was observed. Infection was highly aggregated at the household level and fell close to the 80/20 rule. Using multiple logistic regression analysis clustered by household, infection in dogs was associated positively and significantly with variables reflecting local exposure to infected T. infestans, thus demonstrating weak performance of the vector surveillance system. For high-risk areas in the Gran Chaco region, interruption of vector-mediated domestic transmission of T. cruzi requires residual insecticide spraying that is more intense, of a higher quality and sustained in time, combined with community participation and environmental management measures.

Climatic potential for tourism in the Black Forest, Germany--winter season.

PubMed

Endler, Christina; Matzarakis, Andreas

2011-05-01

Climate change, whether natural or human-caused, will have an impact on human life, including recreation and tourism among other things. In this study, methods from biometeorology and tourism climatology are used to assess the effect of a changed climate on tourism and recreation in particular. The study area is the Black Forest mountainous region of south-west Germany, which is well known for its tourist and recreational assets. Climate model projections for the 2021-2050 period based on REMO-UBA simulations with a high spatial resolution of 10 km are compared to a 30-year reference period (1971-2000) using the IPCC emission scenarios A1B and B1. The results show that the mean winter air temperature will increase by up to 1.8°C, which is the most pronounced warming compared to the other seasons. The annual precipitation amount will increase marginally by 5% in the A1B scenario and 10% in the B1 scenario. Winter precipitation contributes about 10% (A1B) and 30% (B1) to variations in annual precipitation. Although the results show that winter precipitation will increase slightly, snow days affecting skiing will be reduced on average by approximately 40% due to regional warming. Cold stress will be reduced on average by up to 25%. The result is that the thermal environment will be advanced, and warmer winters are likely to lead to an upward altitudinal shift of ski resorts and winter sport activities, thus displacing land-use currently dedicated to nature conservation.

Host genetic variation influences gene expression response to rhinovirus infection.

PubMed

Çalışkan, Minal; Baker, Samuel W; Gilad, Yoav; Ober, Carole

2015-04-01

Rhinovirus (RV) is the most prevalent human respiratory virus and is responsible for at least half of all common colds. RV infections may result in a broad spectrum of effects that range from asymptomatic infections to severe lower respiratory illnesses. The basis for inter-individual variation in the response to RV infection is not well understood. In this study, we explored whether host genetic variation is associated with variation in gene expression response to RV infections between individuals. To do so, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. We mapped local and distant genetic variation that is associated with inter-individual differences in gene expression levels (eQTLs) in both uninfected and RV-infected cells. We focused specifically on response eQTLs (reQTLs), namely, genetic associations with inter-individual variation in gene expression response to RV infection. We identified local reQTLs for 38 genes, including genes with known functions in viral response (UBA7, OAS1, IRF5) and genes that have been associated with immune and RV-related diseases (e.g., ITGA2, MSR1, GSTM3). The putative regulatory regions of genes with reQTLs were enriched for binding sites of virus-activated STAT2, highlighting the role of condition-specific transcription factors in genotype-by-environment interactions. Overall, we suggest that the 38 loci associated with inter-individual variation in gene expression response to RV-infection represent promising candidates for affecting immune and RV-related respiratory diseases.

[Application of 3D printing and computer-assisted surgical simulation in preoperative planning for acetabular fracture].

PubMed

Liu, Xin; Zeng, Can-Jun; Lu, Jian-Sen; Lin, Xu-Chen; Huang, Hua-Jun; Tan, Xin-Yu; Cai, Dao-Zhang

2017-03-20

To evaluate the feasibility and effectiveness of using 3D printing and computer-assisted surgical simulation in preoperative planning for acetabular fractures. A retrospective analysis was performed in 53 patients with pelvic fracture, who underwent surgical treatment between September, 2013 and December, 2015 with complete follow-up data. Among them, 19 patients were treated with CT three-dimensional reconstruction, computer-assisted virtual reset internal fixation, 3D model printing, and personalized surgery simulation before surgery (3D group), and 34 patients underwent routine preoperative examination (conventional group). The intraoperative blood loss, transfusion volume, times of intraoperative X-ray, operation time, Matta score and Merle D' Aubigne & Postel score were recorded in the 2 groups. Preoperative planning and postoperative outcomes in the two groups were compared. All the operations were completed successfully. In 3D group, significantly less intraoperative blood loss, transfusion volume, fewer times of X-ray, and shortened operation time were recorded compared with those in the conventional group (P<0.05). According to the Matta scores, excellent or good fracture reduction was achieved in 94.7% (18/19) of the patients in 3D group and in 82.4% (28/34) of the patients in conventional group; the rates of excellent and good hip function at the final follow-up were 89.5% (17/19) in the 3D group and 85.3% (29/34) in the conventional group (P>0.05). In the 3D group, the actual internal fixation well matched the preoperative design. 3D printing and computer-assisted surgical simulation for preoperative planning is feasible and accurate for management of acetabular fracture and can effectively improve the operation efficiency.

Pelvic reconstructions following peri-acetabular bone tumour resections using a cementless ice-cream cone prosthesis with dual mobility cup.

PubMed

Issa, Samir-Pierre; Biau, David; Babinet, Antoine; Dumaine, Valérie; Le Hanneur, Malo; Anract, Philippe

2018-01-27

Despite numerous reconstructive techniques and prosthetic devices, pelvic reconstructions following peri-acetabular malignant tumours resections are highly challenging. In the present study, we describe our experience with the Integra® (Lépine, Genay, France) ice-cream cone prosthesis in such indications. The objective was to assess the mid-term outcomes of this device. Twenty-four patients' chart with peri-acetabular malignant tumours, who underwent types II or II + III peri-acetabular resections according to Enneking and Dunham with subsequent reconstruction using the Integra® prosthesis between February 2009 and February 2015, were reviewed. Seventeen cases were primary surgeries and seven cases were revisions (i.e., failures of previous reconstructions for pelvic tumours). All living patients with the prosthesis implanted were functionally assessed, using the musculoskeletal tumour society (MSTS) and Postel-Merle d'Aubigné (PMA) scores. After a mean follow-up of 49 ± 26 months (range, 8 to 94 months), 21 patients were alive (88%), including 15 patients continuously disease-free (63%). MSTS and PMA scores averaged 72 ± 13% (range, 43 to 87%) and 14.6 ± 2.6 (range, 9 to 18), respectively. Fourteen patients (58%) presented at least one complication during follow-up, including four cases of deep infection (17%), four cases of dislocation (17%), and two mechanical failures (8%). At 5 years, the implant survival rate was 75%. In comparison to previous reconstructive techniques that we used in similar indications, functional and oncologic outcomes were improved with the Integra® implant. However, as commonly observed in pelvic bone tumour surgery, complication rates remain significant. Therapeutic, Level IV-Retrospective Cases Series.

Offset fémoral et le fonctionnement de la hanche dans la prothèse totale de la hanche

PubMed Central

Rachid, Abdelillah; Moncef, Erraji; Najib, Abbassi; Abdeljaouad, Najib; Abdelkarim, Daudi; Hicham, Yacoubi

2014-01-01

L'offset fémoral est l’élément pronostic le plus important dans l'arthroplastie de la hanche. Sa restauration est devenue de plus en plus une obligation. Toute modification de la valeur native de l'offset retenti sur la qualité du fonctionnement clinique de la hanche. Le but de notre travail était d’évaluer le fonctionnement clinique de la hanche en fonction de la valeur de l'offset fémoral après une arthroplastie. C'est une étude rétrospective effectuée entre 2010 et 2013, comportant 27 patients ayant bénéficiés d'une arthroplastie totale de la hanche. Les patients ayant eu un geste chirurgicale antérieur sur la même hanche ou sur la hanche controlatérale ont été exclus. Les mesures ont été effectuées sur des radiographies standards de la hanche en rotation interne d'environ 15°, avec un agrandissement à 100%. Les résultats cliniques étaient évalués au moyen du score de WOMAC qui était en moyenne de 15,2 points, et le score de Merle d'Aubigné-Postel avec une moyenne de 15 points. Deux autres tests ont été évalués dans notre étude qui sont le step et le hop test. Les meilleurs résultats fonctionnels ont été obtenus chez les patients ayant eu une latéralisation de la tige fémoral avec un offset augmenté. PMID:25400835

[Ceramic-ceramic articulation in uncemented total hip arthroplasty].

PubMed

Synder, Marek; Drobniewski, Marek; Kozłowski, Piotr; Grzegorzewski, Andrzej

2005-01-01

The main problem in total hip arthroplasty (THA) surgery is aseptic loosening of prosthesis components. In most cases the phagocytes reaction against the wear particle during the hip movement is responsible for aseptic prosthesis loosening. To prevent this reaction different hip articulation are invented to reduce this reaction. One of these solutions is ceramic-ceramic hip prosthesis articulation. The aim of this study was to evaluate the long-term results in patients who were treated because of coxarthrosis by means of ceramic-ceramic hip prosthesis. We analyzed 258 primary THA (222 patients, 116 women and 106 men) who were treated because of advanced coxarthrosis by Mittelmeier type hip endoprosthesis (ceramic-ceramic articulation). The mean age of patients at the surgery was 45.6 years and a mean follow-up 10.2 years. In most of our cases the idiopathic, traumatic and dysplastic coxarthrosis was noted. For clinical evaluation the classification system proposed by Merle d'Aubigne and Postel with Charnley modification was used. For radiological evaluation of the steam implantation the classification system proposed by De Lee and Charnley was used and for the cup implantation the system by Gruen and Moreland. In 87 patients (33.7%) the final results was graded as very good, in 96 (37.2%) as good, in 47 (18.2%) as satisfactory and in 28 patients (10.9%) the final results was poor. In analyzed group in 13 patients (5.0%) the revision surgery was necessary. The long-term results of THA with the use of Mittelmeier type of hip prosthesis presented a very low percentage of aseptic loosening. This type of prosthesis gives very high patients satisfaction.

Comparative study of comminuted posterior acetabular wall fracture treated with the Acetabular Tridimensional Memory Fixation System.

PubMed

Zhang, Yuntong; Zhao, Xue; Tang, Yang; Zhang, Chuncai; Xu, Shuogui; Xie, Yang

2014-04-01

Posterior wall fractures are one of the most common acetabular fractures. However, only 30% of these fractures involve a single large fragment, and comminuted acetabular posterior wall fractures pose a particular surgical challenge. The purpose of this study was to compare outcomes between patients who received fixation for comminuted posterior wall fracture using the Acetabular Tridimensional Memory Fixation System (ATMFS) and patients who underwent fixation with conventional screws and buttress plates (Plates group). Between April 2003 and May 2007, 196 consecutive patients who sustained a comminuted posterior wall fracture of acetabulum were treated with ATMFS or conventional screws and buttress plates. Operative time, fluoroscopy time, blood loss, and any intra-operative complications were recorded. Plain AP and lateral radiographs were obtained at all visits (Matta's criteria). Modified Merle d' Aubigne-Postel score, and Mos SF-36 score were compared between groups. Fifty patients were included in the analysis with 26 in the ATMFS group and 24 in the Plates group. The mean follow-up time was 57.5 months, ranging from 31 to 69 months. All patients had fully healed fractures at the final follow-up. There was no difference in clinical outcomes or radiological evaluations between groups. Patients with comminuted posterior wall fractures of the acetabulum treated with the ATMFS or conventional screws and buttress plate techniques achieve a good surgical result. Both techniques are safe, reliable, and practical. Use of the ATMFS technique may reduce blood loss and improve rigid support to marginal bone impaction. The use ATMFS may need additional support when fractures involve the superior roof. Copyright © 2013 Elsevier Ltd. All rights reserved.

Management of acetabular fractures with modified posterior approach to spare external hip rotators.

PubMed

Sarlak, Ahmet Y; Selek, Ozgur; Inanir, Murat; Musaoglu, Resul; Baran, Tuncay

2014-04-01

In the present study the quality of reduction and incidence of complications in hip external rotator sparing modified posterior approach was assessed in both simple and complex acetabular fractures. This retrospective study includes 37 patients (38 hips) with a mean age of 42.1 years (range 21-60), that had been treated for displaced acetabular fractures from June 2007 through May 2011. They were reviewed at a mean of 3 years (20-67 months). The fractures were classified according to the Letournel-Judet classification. Anatomic reduction and stable fixation of the fracture with less than 2mm residual displacement was achieved in 28 of 38 hips. At the final follow up the patients were evaluated clinically according to Merle d'Aubigne and Postel scoring system which had been modified by Matta and radiologically based on the criteria described by Matta. The clinical results were excellent in 20, good in 8, fair in 8, and poor 2 hips. Complications included two superficial local wound infection and 10 heterotopic ossification with 7 of the cases having grade I heterotopic ossification. Avascular necrosis of the femoral head was not seen in any of the 38 hips. One patient with preoperative sciatic nerve palsy had complete recovery of neurologic function. There were no cases of deep vein thrombosis or pulmonary embolism. The functional outcome was satisfactory in most of the cases and comparable with other larger series. Using the limited part of Henry's sciatic nerve exposure skin incision - working in the plane between gluteus maximus and the tensor fascia lata as in the classical Gibson approach and two portal external rotator hip sparing approach resulted in good fracture reduction without approach related complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Archaeal Inorganic Pyrophosphatase Displays Robust Activity under High-Salt Conditions and in Organic Solvents.

PubMed

McMillan, Lana J; Hepowit, Nathaniel L; Maupin-Furlow, Julie A

2016-01-15

Soluble inorganic pyrophosphatases (PPAs) that hydrolyze inorganic pyrophosphate (PPi) to orthophosphate (Pi) are commonly used to accelerate and detect biosynthetic reactions that generate PPi as a by-product. Current PPAs are inactivated by high salt concentrations and organic solvents, which limits the extent of their use. Here we report a class A type PPA of the haloarchaeon Haloferax volcanii (HvPPA) that is thermostable and displays robust PPi-hydrolyzing activity under conditions of 25% (vol/vol) organic solvent and salt concentrations from 25 mM to 3 M. HvPPA was purified to homogeneity as a homohexamer by a rapid two-step method and was found to display non-Michaelis-Menten kinetics with a Vmax of 465 U · mg(-1) for PPi hydrolysis (optimal at 42°C and pH 8.5) and Hill coefficients that indicated cooperative binding to PPi and Mg(2+). Similarly to other class A type PPAs, HvPPA was inhibited by sodium fluoride; however, hierarchical clustering and three-dimensional (3D) homology modeling revealed HvPPA to be distinct in structure from characterized PPAs. In particular, HvPPA was highly negative in surface charge, which explained its extreme resistance to organic solvents. To demonstrate that HvPPA could drive thermodynamically unfavorable reactions to completion under conditions of reduced water activity, a novel coupled assay was developed; HvPPA hydrolyzed the PPi by-product generated in 2 M NaCl by UbaA (a "salt-loving" noncanonical E1 enzyme that adenylates ubiquitin-like proteins in the presence of ATP). Overall, we demonstrate HvPPA to be useful for hydrolyzing PPi under conditions of reduced water activity that are a hurdle to current PPA-based technologies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Dessau workshop on bioaccumulation: state of the art, challenges and regulatory implications.

PubMed

Treu, Gabriele; Drost, Wiebke; Jöhncke, Ulrich; Rauert, Caren; Schlechtriem, Christian

2015-01-01

Bioaccumulation plays a vital role in understanding the fate of a substance in the environment and is key to the regulation of chemicals in several jurisdictions. The current assessment approaches commonly use the octanol-water partition coefficient (log K OW ) as an indicator for bioaccumulation and the bioconcentration factor (BCF) as a standard criterion to identify bioaccumulative substances show limitations. The log K OW does not take into account active transport phenomena or special structural properties (e.g., amphiphilic substances or dissociating substances) and therefore additional screening criteria are required. Regulatory BCF studies are so far restricted to fish and uptake through the gills. Studies on (terrestrial) air-breathing organisms are missing. Though there are alternative tests such as the dietary exposure bioaccumulation fish test described in the recently revised OECD test guideline 305, it still remains unclear how to deal with results of alternative tests in regulatory decision-making processes. A substantial number of bioaccumulation fish tests are required in regulation. The development of improved test systems following the 3R principles, namely to replace, reduce and refine animal testing, is thus required. All these aspects stress the importance to further develop the assessment of bioaccumulation. The Dessau Workshop on Bioaccumulation which was held from June 26th to 27th 2014, in Dessau, Germany, provided a comprehensive overview of the state of the art of bioaccumulation assessment, provided insights into the problems and challenges addressed by the regulatory authorities and described new research concepts and their regulatory implications. The event was organised by UBA (Dessau, Germany) and Fraunhofer IME (Schmallenberg, Germany). About 50 participants from industry, regulatory bodies and academia listened to 14 lectures on selected topics and joined the plenary discussions.

Antiviral activity of A771726, the active metabolite of leflunomide, against Junín virus.

PubMed

Sepúlveda, Claudia S; García, Cybele C; Damonte, Elsa B

2018-05-01

The aim of this study was to investigate the effect of A771726, the active metabolite of leflunomide, (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad against the infection with Junín virus (JUNV), agent of Argentine hemorrhagic fever (AHF). The treatment with non-cytotoxic concentrations of A771726 of Vero and A549 cells infected with JUNV inhibited virus replication in a dose-dependent manner, as determined by virus yield reduction assay. The antiviral effectiveness of A771726 was not importantly affected by the multiplicity of infection and the virus strain. Moreover, the combination of A771726 and ribavirin had a significantly more potent antiviral activity than each single drug treatment. Mechanistic studies showed that the main action of A771726 is exerted before 6 h of JUNV infection. Accordingly, inhibition of viral RNA synthesis was detected in treated infected cells by real time RT-PCR. The exogenous addition of uridine or orotic acid produced a partial reversal of the inhibitory effect of A771726 on infective virus production whereas a total reversion was detected on JUNV RNA synthesis, probably by restoration of the enzymatic activity of dihydroorotate dehydrogenase (DHODH) and the intracellular pyrimidine pools. In conclusion, these results suggest that the antiviral target would be viral RNA synthesis through pyrimidine depletion, but any other effect of the compound on JUNV infection cannot be excluded. This study opens the possibility of the therapeutic application of a wide spectrum host-targeted compound alone or in combination with ribavirin to combat AHF as well as other human pathogenic arenaviruses. © 2018 Wiley Periodicals, Inc.

Role of Mex67-Mtr2 in the Nuclear Export of 40S Pre-Ribosomes

PubMed Central

Occhipinti, Laura; Kemmler, Stefan; Panse, Vikram G.

2012-01-01

Nuclear export of mRNAs and pre-ribosomal subunits (pre40S and pre60S) is fundamental to all eukaryotes. While genetic approaches in budding yeast have identified bona fide export factors for mRNAs and pre60S subunits, little is known regarding nuclear export of pre40S subunits. The yeast heterodimeric transport receptor Mex67-Mtr2 (TAP-p15 in humans) binds mRNAs and pre60S subunits in the nucleus and facilitates their passage through the nuclear pore complex (NPC) into the cytoplasm by interacting with Phe-Gly (FG)-rich nucleoporins that line its transport channel. By exploiting a combination of genetic, cell-biological, and biochemical approaches, we uncovered an unanticipated role of Mex67-Mtr2 in the nuclear export of 40S pre-ribosomes. We show that recruitment of Mex67-Mtr2 to pre40S subunits requires loops emanating from its NTF2-like domains and that the C-terminal FG-rich nucleoporin interacting UBA-like domain within Mex67 contributes to the transport of pre40S subunits to the cytoplasm. Remarkably, the same loops also recruit Mex67-Mtr2 to pre60S subunits and to the Nup84 complex, the respective interactions crucial for nuclear export of pre60S subunits and mRNAs. Thus Mex67-Mtr2 is a unique transport receptor that employs a common interaction surface to participate in the nuclear export of both pre-ribosomal subunits and mRNAs. Mex67-Mtr2 could engage a regulatory crosstalk among the three major export pathways for optimal cellular growth and proliferation. PMID:22956913

Monitoring autophagic flux using p62/SQSTM1 based luciferase reporters in glioma cells.

PubMed

Min, Zhang; Ting, Yao; Mingtao, Gong; Xiaofei, Tang; Dong, Yan; Chenguang, Zhang; Wei, Ding

2018-02-01

Autophagy is a highly dynamic process characterized with the term of autophagic flux. In the present study, we developed a quantifiable luciferase reporter system to measure the capacity as well as the dynamics of autophagic flux. Briefly, a luciferase variant of Luc2p was fused with p62/SQSTM1 or its UBA domain deletion mutant (p62ΔU) and transfected into cells. The expressed Luc2p-p62 fusion protein was primarily degraded via autophagy, while Luc2p-p62ΔU was employed as a normalization control due to its resistance to autophagic degradation. The luciferase activity of the lysates from two parallel populations of glioma cells expressing either Luc2p-p62 or Luc2p-p62ΔU was determined and the ratio of Luc2p-p62ΔU/Luc2p-p62 was used to assay the autophagic flux. By this approach, the induction of autophagy was manifested as an increased Luc2p-p62ΔU/Luc2p-p62 ratio, which could be neutralized by autophagy inhibitors or knockdown of ATG5. The performance of our autophagic flux detection system was comparable to a recently reported GFP-LC3-RFP-LC3ΔG probe. We tested the system in TMZ treated glioma cells, and found that coadministration of chloroquine to attenuate cellular autophagic flux significantly improved the TMZ efficacy by triggering more early apoptosis. Collectively, our luciferase-based autophagic flux assay may serve as a useful alternative yet sensitive method for autophagic flux detection in tumor cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Identification of potential target genes and related regulatory transcription factors in spontaneous hairline fracture induced by hypervitaminosis A.

PubMed

Peng, Chuangang; Yang, Qi; Wei, Bo; Liu, Yong; Li, Yuxiang; Gu, Dawei; Yin, Guochao; Wang, Bo; Xu, Dehui; Zhang, Xuebing; Kong, Daliang

2017-07-01

The aim was to research the molecular changes of bone cells induced by excessive dose of vitamin A, and analyze molecular mechanism underlying spontaneous fracture. The gene expression profile of GSE29859, including 4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DGEs) between cortical bone marrow samples and control samples were screened out and pathway enrichment analysis was undertaken. Based on the MSigDB database, the potential regulatory transcription factors (TFs) were identified. A total of 373 DEGs including 342 up- and 31 down-regulated genes were identified. These DEGs were significantly enriched in pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism. Finally, the most significant regulatory TFs were obtained, including E2F Transcription Factor 1 (E2F1), GA Binding Protein Transcription Factor (GABP), Nuclear Factor, Erythroid 2-Like 2 (NRF2) and ELK1, Member of ETS Oncogene Family (ELK1). Key TFs including E2F1, GABP, NRF2 and ELK1 and their targets genes such as Ube2d3, Uba1, Phb2 and Tomm22 may play potential key roles in spontaneous fracture induced by hypervitaminosis A. The pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism may be key mechanisms involved in spontaneous fracture induced by hypervitaminosis A. Our findings will provide new insights for the target selection in clinical application to prevent spontaneous fracture induced by hypervitaminosis A. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of acute and chronic methamphetamine administration on cynomolgus monkey hippocampus structure and cellular transcriptome.

PubMed

Choi, Mi Ran; Chun, Ji-Won; Kwak, Su Min; Bang, Sol Hee; Jin, Yeung-Bae; Lee, Youngjeon; Kim, Han-Na; Chang, Kyu-Tae; Chai, Young Gyu; Lee, Sang-Rae; Kim, Dai-Jin

2018-05-23

Methamphetamine (MA), a psychostimulant abused worldwide, gives rise to neurotoxicity in the hippocampus, resulting in cognitive impairments and hippocampal volume reduction. The cellular and molecular mechanisms associated with hippocampal impairments due to MA remain unknown. The aim of this study was to investigate the effects of MA on structural alterations and gene expressions in the hippocampus. We analyzed the pattern of volumetric changes in the hippocampus using magnetic resonance imaging (MRI) after acute and chronic administration of MA to cynomolgus macaques. In addition, we performed large-scale transcriptome profiling in the hippocampus using RNA-Seq technology. The hippocampus in response to acute and chronic MA exhibited a significant volumetric atrophy compared with the hippocampus of controls. The genes associated with cytoskeleton organization and phagocytosis were downregulated in the acute MA-treated group compared to the control group. On the other hand, genes associated with synaptic transmission, regulation of neuron differentiation and regulation of neurogenesis were downregulated in the chronic MA-treated group. We confirmed that expression patterns for ADM, BMP4, CHRD, PDYN, UBA1, profilin 2 (PFN2), ENO2 and NSE mRNAs were similar to the results from RNA-Seq based on quantitative RT-PCR. In particular, PFN2 mRNA and protein expression levels, which play important roles in actin cytoskeleton dynamics, were decreased by acute and chronic MA administration. These results not only aid the understanding of cellular and molecular mechanisms regulated by MA in the hippocampus but also suggest basic information aiding biomarker and novel drug development for treating hippocampal impairment caused by MA abuse. Copyright © 2017. Published by Elsevier Inc.

Accumulation and detoxification dynamics of Chromium and antioxidant responses in juvenile rare minnow, Gobiocypris rarus.

PubMed

Yuan, Cong; Li, Meng; Zheng, Yao; Zhou, Ying; Wu, Feili; Wang, Zaizhao

2017-09-01

Hexavalent chromium (Cr 6+ ) compounds are hazardous via all exposure routes. To explore the dynamics of Cr accumulation and elimination and to reveal the mechanisms underlying detoxification and antioxidation in juvenile Gobiocypris rarus, one-month old G. rarus larvae were exposed to 0.1mgL -1 Cr 6+ for four weeks for accumulation and subsequently placed to clean water for another week for depuration. The contents of Cr were measured weekly in the whole body of G. rarus juveniles. The activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione reductase (GR), and contents of glutathione (GSH) and malonaldehyde (MDA), and transcripts of cat, Cu/Zn-sod, Mn-sod, gpx1, gstpi, gr, mt1, nrf2 and uba52 were determined. The results indicated that G. rarus juveniles had a strong ability to resist the Cr accumulation by Cr 6+ exposure and to remove Cr from the body in clean water. In addition, GST and MT proteins may be involved in the detoxification of Cr 6+ . Moreover, Cr 6+ -induced GST detoxification in G. rarus juveniles might be accomplished through the Nrf2-mediated regulation of gene expressions. The antioxidant enzyme systems exhibited a response mechanism of the protective enzymes in organisms when they are subjected to external environmental stress. Two weeks of Cr 6+ treatments could have led to the damage and consecutive degradation of antioxidant enzymes via ubiquitination, and MT proteins could be involved in protecting the activity of these enzymes. The capability of antioxidant enzyme systems to recover from the Cr 6+ -induced damage was strong in G. rarus juveniles after Cr 6+ was removed from the water. Copyright © 2017 Elsevier B.V. All rights reserved.

Transposon mutagenesis identifies genes and cellular processes driving epithelial-mesenchymal transition in hepatocellular carcinoma

PubMed Central

Kodama, Takahiro; Newberg, Justin Y.; Kodama, Michiko; Rangel, Roberto; Yoshihara, Kosuke; Tien, Jean C.; Parsons, Pamela H.; Wu, Hao; Finegold, Milton J.; Copeland, Neal G.; Jenkins, Nancy A.

2016-01-01

Epithelial-mesenchymal transition (EMT) is thought to contribute to metastasis and chemoresistance in patients with hepatocellular carcinoma (HCC), leading to their poor prognosis. The genes driving EMT in HCC are not yet fully understood, however. Here, we show that mobilization of Sleeping Beauty (SB) transposons in immortalized mouse hepatoblasts induces mesenchymal liver tumors on transplantation to nude mice. These tumors show significant down-regulation of epithelial markers, along with up-regulation of mesenchymal markers and EMT-related transcription factors (EMT-TFs). Sequencing of transposon insertion sites from tumors identified 233 candidate cancer genes (CCGs) that were enriched for genes and cellular processes driving EMT. Subsequent trunk driver analysis identified 23 CCGs that are predicted to function early in tumorigenesis and whose mutation or alteration in patients with HCC is correlated with poor patient survival. Validation of the top trunk drivers identified in the screen, including MET (MET proto-oncogene, receptor tyrosine kinase), GRB2-associated binding protein 1 (GAB1), HECT, UBA, and WWE domain containing 1 (HUWE1), lysine-specific demethylase 6A (KDM6A), and protein-tyrosine phosphatase, nonreceptor-type 12 (PTPN12), showed that deregulation of these genes activates an EMT program in human HCC cells that enhances tumor cell migration. Finally, deregulation of these genes in human HCC was found to confer sorafenib resistance through apoptotic tolerance and reduced proliferation, consistent with recent studies showing that EMT contributes to the chemoresistance of tumor cells. Our unique cell-based transposon mutagenesis screen appears to be an excellent resource for discovering genes involved in EMT in human HCC and potentially for identifying new drug targets. PMID:27247392

Combined miRNA profiling and proteomics demonstrates that different miRNAs target a common set of proteins to promote colorectal cancer metastasis.

PubMed

Torres, Sofía; Garcia-Palmero, Irene; Bartolomé, Rubén A; Fernandez-Aceñero, María Jesús; Molina, Elena; Calviño, Eva; Segura, Miguel F; Casal, J Ignacio

2017-05-01

The process of liver colonization in colorectal cancer remains poorly characterized. Here, we addressed the role of microRNA (miRNA) dysregulation in metastasis. We first compared miRNA expression profiles between colorectal cancer cell lines with different metastatic properties and then identified target proteins of the dysregulated miRNAs to establish their functions and prognostic value. We found that 38 miRNAs were differentially expressed between highly metastatic (KM12SM/SW620) and poorly metastatic (KM12C/SW480) cancer cell lines. After initial validation, we determined that three miRNAs (miR-424-3p, -503, and -1292) were overexpressed in metastatic colorectal cancer cell lines and human samples. Stable transduction of non-metastatic cells with each of the three miRNAs promoted metastatic properties in culture and increased liver colonization in vivo. Moreover, miR-424-3p and miR-1292 were associated with poor prognosis in human patients. A quantitative proteomic analysis of colorectal cancer cells transfected with miR-424-3p, miR-503, or miR-1292 identified alterations in 149, 129, or 121 proteins, respectively, with an extensive overlap of the target proteins of the three miRNAs. Importantly, down-regulation of two of these shared target proteins, CKB and UBA2, increased cell adhesion and proliferation in colorectal cancer cells. The capacity of distinct miRNAs to regulate the same mRNAs boosts the capacity of miRNAs to regulate cancer metastasis and underscores the necessity of targeting multiple miRNAs for effective cancer therapy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Archaeal Inorganic Pyrophosphatase Displays Robust Activity under High-Salt Conditions and in Organic Solvents

PubMed Central

McMillan, Lana J.; Hepowit, Nathaniel L.

2015-01-01

Soluble inorganic pyrophosphatases (PPAs) that hydrolyze inorganic pyrophosphate (PPi) to orthophosphate (Pi) are commonly used to accelerate and detect biosynthetic reactions that generate PPi as a by-product. Current PPAs are inactivated by high salt concentrations and organic solvents, which limits the extent of their use. Here we report a class A type PPA of the haloarchaeon Haloferax volcanii (HvPPA) that is thermostable and displays robust PPi-hydrolyzing activity under conditions of 25% (vol/vol) organic solvent and salt concentrations from 25 mM to 3 M. HvPPA was purified to homogeneity as a homohexamer by a rapid two-step method and was found to display non-Michaelis-Menten kinetics with a Vmax of 465 U · mg−1 for PPi hydrolysis (optimal at 42°C and pH 8.5) and Hill coefficients that indicated cooperative binding to PPi and Mg2+. Similarly to other class A type PPAs, HvPPA was inhibited by sodium fluoride; however, hierarchical clustering and three-dimensional (3D) homology modeling revealed HvPPA to be distinct in structure from characterized PPAs. In particular, HvPPA was highly negative in surface charge, which explained its extreme resistance to organic solvents. To demonstrate that HvPPA could drive thermodynamically unfavorable reactions to completion under conditions of reduced water activity, a novel coupled assay was developed; HvPPA hydrolyzed the PPi by-product generated in 2 M NaCl by UbaA (a “salt-loving” noncanonical E1 enzyme that adenylates ubiquitin-like proteins in the presence of ATP). Overall, we demonstrate HvPPA to be useful for hydrolyzing PPi under conditions of reduced water activity that are a hurdle to current PPA-based technologies. PMID:26546423

Participation in environmental enhancement and conservation activities for health and well-being in adults: a review of quantitative and qualitative evidence.

PubMed

Husk, Kerryn; Lovell, Rebecca; Cooper, Chris; Stahl-Timmins, Will; Garside, Ruth

2016-05-21

There is growing research and policy interest in the potential for using the natural environment to enhance human health and well-being. This resource may be underused as a health promotion tool to address the increasing burden of common health problems such as increased chronic diseases and mental health concerns. Outdoor environmental enhancement and conservation activities (EECA) (for instance unpaid litter picking, tree planting or path maintenance) offer opportunities for physical activity alongside greater connectedness with local environments, enhanced social connections within communities and improved self-esteem through activities that improve the locality which may, in turn, further improve well-being. To assess the health and well-being impacts on adults following participation in environmental enhancement and conservation activities. We contacted or searched the websites of more than 250 EECA organisations to identify grey literature. Resource limitations meant the majority of the websites were from UK, USA, Canada and Australia. We searched the following databases (initially in October 2012, updated October 2014, except CAB Direct, OpenGrey, SPORTDiscus, and TRIP Database), using a search strategy developed with our project advisory groups (predominantly leaders of EECA-type activities and methodological experts): ASSIA; BIOSIS; British Education Index; British Nursing Index; CAB Abstracts; Campbell Collaboration; Cochrane Public Health Specialized Register; DOPHER; EMBASE; ERIC; Global Health; GreenFILE; HMIC; MEDLINE-in-Process; MEDLINE; OpenGrey; PsychINFO; Social Policy and Practice; SPORTDiscus; TRoPHI; Social Services Abstracts; Sociological Abstracts; The Cochrane Library; TRIP database; and Web of Science. Citation and related article chasing was used. Searches were limited to studies in English published after 1990. Two review authors independently screened studies. Included studies examined the impact of EECA on adult health and well-being. Eligible interventions needed to include each of the following: intended to improve the outdoor natural or built environment at either a local or wider level; took place in urban or rural locations in any country; involved active participation; and were NOT experienced through paid employment.We included quantitative and qualitative research. Includable quantitative study designs were: randomised controlled trials (RCTs), cluster RCTs, quasi-RCTs, cluster quasi-RCTs, controlled before-and-after studies, interrupted-time-series, cohort studies (prospective or retrospective), case-control studies and uncontrolled before-and-after studies (uBA). We included qualitative research if it used recognised qualitative methods of data collection and analysis. One reviewer extracted data, and another reviewer checked the data. Two review authors independently appraised study quality using the Effective Public Health Practice Project tool (for quantitative studies) or Wallace criteria (for qualitative studies). Heterogeneity of outcome measures and poor reporting of intervention specifics prevented meta-analysis so we synthesised the results narratively. We synthesised qualitative research findings using thematic analysis. Database searches identified 21,420 records, with 21,304 excluded at title/abstract. Grey literature searches identified 211 records. We screened 327 full-text articles from which we included 21 studies (reported in 28 publications): two case-studies (which were not included in the synthesis due to inadequate robustness), one case-control, one retrospective cohort, five uBA, three mixed-method (uBA, qualitative), and nine qualitative studies. The 19 studies included in the synthesis detailed the impacts to a total of 3,603 participants: 647 from quantitative intervention studies and 2630 from a retrospective cohort study; and 326 from qualitative studies (one not reporting sample size).Included studies shared the key elements of EECA defined above, but the range of activities varied considerably. Quantitative evaluation methods were heterogeneous. The designs or reporting of quantitative studies, or both, were rated as 'weak' quality with high risk of bias due to one or more of the following: inadequate study design, intervention detail, participant selection, outcome reporting and blinding.Participants' characteristics were poorly reported; eight studies did not report gender or age and none reported socio-economic status. Three quantitative studies reported that participants were referred through health or social services, or due to mental ill health (five quantitative studies), however participants' engagement routes were often not clear.Whilst the majority of quantitative studies (n = 8) reported no effect on one or more outcomes, positive effects were reported in six quantitative studies relating to short-term physiological, mental/emotional health, and quality-of-life outcomes. Negative effects were reported in two quantitative studies; one study reported higher levels of anxiety amongst participants, another reported increased mental health stress.The design or reporting, or both, of the qualitative studies was rated as good in three studies or poor in nine; mainly due to missing detail about participants, methods and interventions. Included qualitative evidence provided rich data about the experience of participation. Thematic analysis identified eight themes supported by at least one good quality study, regarding participants' positive experiences and related to personal/social identity, physical activity, developing knowledge, spirituality, benefits of place, personal achievement, psychological benefits and social contact. There was one report of negative experiences. There is little quantitative evidence of positive or negative health and well-being benefits from participating in EECA. However, the qualitative research showed high levels of perceived benefit among participants. Quantitative evidence resulted from study designs with high risk of bias, qualitative evidence lacked reporting detail. The majority of included studies were programme evaluations, conducted internally or funded by the provider.The conceptual framework illustrates the range of interlinked mechanisms through which people believe they potentially achieve health and well-being benefits, such as opportunities for social contact. It also considers potential moderators and mediators of effect.One main finding of the review is the inherent difficulty associated with generating robust evidence of effectiveness for complex interventions. We developed the conceptual framework to illustrate how people believed they benefited. Investigating such mechanisms in a subsequent theory-led review might be one way of examining evidence of effect for these activities.The conceptual framework needs further refinement through linked reviews and more reliable evidence. Future research should use more robust study designs and report key intervention and participant detail.

Correlation of Chemical and Physical Test Data For the Environment Ageing of Coflon (PVDF). Revised

NASA Technical Reports Server (NTRS)

Morgan, G. J.; Campion, R. P.

1997-01-01

This report aims to identify correlations between mechanical property changes and chemical/morphological structure changes for Coflon. It is intended both to illustrate the overall methodology and to indicate the testing that needs to be undertaken in order to obtain correlations. Many fluid exposures have now been carried out on Coflon during the project and many data generated as a result. The report summarises the changes observed in mechanical and physical properties and relates these as well as possible to the chemistry thought to be occurring during ageing. For this purpose, data have been collated from already-issued MERL and TRI technical and progress reports. Most of the mechanical testing of aged testpieces has been performed soon after the completion of the exposure; however, there is of necessity a delay in obtaining chemical analysis of the same testpieces, so that more physical than chemical data are shown. Three fluids have so far caused measurable deterioration of Coflon, these being: methanol (Fluid A), a methanol and amine mixture (Fluid G), and a mixture of methane, carbon dioxide gas and hydrogen sulphide gas plus aqueous amine (Fluid F). Only the effects of these fluids will be dealt with in any detail in this report, although other fluids are assessed to give relevant background information. Relevant test data collated here include: tensile modulus and related properties, mode of sample failure at break, fracture toughness, fatigue crack growth rate and resistance, stress relaxation rate, permeation coefficients, % crystallinity and molecular weight distributions together with changes in fluorine levels, and other observations where appropriate. However, not all of these were obtained for every ageing condition. Because of the wide range of tests employed, and the different ways in which their results are obtained, the following section has been included to serve as a background for making comparisons.

The Influence of Crustal Thickness and Slope on the Surface Morphology of Active Lava Flows: an Experimental Approach

NASA Astrophysics Data System (ADS)

Applegarth, L. J.; James, M. R.; van Wyk de Vries, B.; Pinkerton, H.

2007-12-01

Many of the surface features that develop on `a`a and blocky lava flows relate to internal dynamics during flow emplacement, but it can be difficult to infer the precise relationships between morphology and dynamics from observations of flows either during or after their emplacement. Experiments using PEG have greatly improved our understanding of the behaviour of lavas with relatively thin crusts. Here we describe an alternative approach (similar to that of Lescinsky and Merle (2005), GSA Special Paper 396, p.136) in which the crust plays a significant role in flow development. Our experiments investigated the effect of crustal thickness and slope on the morphological development of channelised distal flows. The materials used were high viscosity (104 Pa s) silicone gel to simulate the still-fluid lava, and a mix of sand and plaster to represent the cohesive brittle crust and the confining levees. Experiments were conducted on an inclined board with a reservoir constructed at one end. Silicone was released from the reservoir through a sliding gate, where it encountered a seed flow consisting of a silicone sheet topped with a crust of known depth and constrained by levees. The models therefore represented the influx of fresh lava into a channel. Sequential digital images taken over the course of each experiment allowed marker points on the flow surface to be tracked, and these data were used to construct surface velocity maps. Several experiments were recorded using stereo imagery, allowing changes in the surface relief to be monitored. The insights from these quantitative techniques, combined with morphological observations, are used to illustrate the effect of the crust on the flow dynamics, and to show the response of the brittle crust to the movement of the viscous flow interior. An overview of the experimental techniques and results will be presented, together with an assessment of how the observed model morphologies can be related to features observed in the field.

[Correlation analysis between residual displacement and hip function after reconstruction of acetabular fractures].

PubMed

Ma, Kunlong; Fang, Yue; Luan, Fujun; Tu, Chongqi; Yang, Tianfu

2012-03-01

To investigate the relationships between residual displacement of weight-bearing and non weight-bearing zones (gap displacement and step displacement) and hip function by analyzing the CT images after reconstruction of acetabular fractures. The CT measures and clinical outcome were retrospectively analyzed from 48 patients with displaced acetabular fracture between June 2004 and June 2009. All patients were treated by open reduction and internal fixation, and were followed up 24 to 72 months (mean, 36 months); all fractures healed after operation. The residual displacement involved the weight-bearing zone in 30 cases (weight-bearing group), and involved the non weight-bearing zone in 18 cases (non weight-bearing group). The clinical outcomes were evaluated by Merle d'Aubigné-Postel criteria, and the reduction of articular surface by CT images, including the maximums of two indexes (gap displacement and step displacement). All the data were analyzed in accordance with the Spearman rank correlation coefficient analysis. There was strong negative correlation between the hip function and the residual displacement values in weight-bearing group (r(s) = -0.722, P = 0.001). But there was no correlation between the hip function and the residual displacement values in non weight-bearing group (r(s) = 0.481, P = 0.059). The results of clinical follow-up were similar to the correlation analysis results. In weight-bearing group, the hip function had strong negative correlation with step displacement (r(s) = 0.825, P = 0.002), but it had no correlation with gap displacement (r(s) = 0.577, P = 0.134). In patients with acetabular fracture, the hip function has correlation not only with the extent of the residual displacement but also with the location of the residual displacement, so the residual displacement of weight-bearing zone is a key factor to affect the hip function. In patients with residual displacement in weight-bearing zone, the bigger the step displacement is, the worse the hip function is.

Conservation of prehistoric caves and stability of their inner climate: lessons from Chauvet and other French caves.

PubMed

Bourges, F; Genthon, P; Genty, D; Lorblanchet, M; Mauduit, E; D'Hulst, D

2014-09-15

In the last 150 years, some prehistoric painted caves suffered irreversible degradations due to misperception of conservation issues and subsequent mismanagement. These sites presented naturally an exceptional stability of their internal climate allowing conservation in situ of outstanding fragile remains, some for nearly 40,000 years. This is for a large part due to exchanges of air, CO2, heat and water with the karstic system in which these caves are included. We introduce the concept of underground confinement, based on the stability of the inner cave climate parameters, especially its temperature. Confined caves present the best conservative properties. It is emphasized that this confined state implies slow exchanges with the surrounding karst and that a stable cave cannot be viewed as a closed system. This is illustrated on four case studies of French caves of various confinement states evidenced by long term continuous monitoring and on strategies to improve their conservation properties. The Chauvet cave presents optimal conservation properties. It is wholly confined as shown by the stability of its internal parameters since its discovery in 1994. In Marsoulas cave, archeological works removed the entrance scree and let a strong opening situation of the decorated zone. Remediation is expected by adding a buffer structure at the entrance. In Pech Merle tourist cave, recurrent painting fading was related to natural seasonal drying of walls. Improvement of the cave closure system restored a confined state insuring optimal visibility of the paintings. In Gargas tourist cave, optimization of closures, lighting system and number of visitors, allowed it to gradually reach a semi-confined state that improved the conservation properties. Conclusions are drawn on the characterization of confinement state of caves and on the ways to improve their conservation properties by restoring their initial regulation mechanisms and to avoid threats to their stability. Copyright © 2013 Elsevier B.V. All rights reserved.

Les fractures luxations du cotyle: prise en charge et pronostic à long terme; étude rétrospective portant sur 40 cas

PubMed Central

Chagou, Aniss; Hmouri, Ismail; Rhanim, Abdelkarim; Lahlou, Abdou; Berrada, Mohammed Saleh; Yaacoubi, Moradh

2014-01-01

Les fractures luxations du cotyle sont le plus souvent dues à des traumatismes de haute énergie. Elles constituent une urgence thérapeutique, l'association de la luxation à une fracture du cotyle fait apparaître la question du choix thérapeutique entre traitement orthopédique et traitement médical. L'objectif de l’étude est de mettre le point sur l'aspect thérapeutique dans ces lésions mais aussi leurs pronostics à long terme. Nous rapportons une étude rétrospective portant sur 40 cas colligés au service d'orthopédie du centre hospitalier universitaire de Rabat. Nous avons évalué les résultats de notre prise en charge mais aussi le pronostic à court et à long terme. Dans notre série, vingt cinq patients ont bénéficié d'un traitement orthopédique alors que les quinze restants ont été opérés, la voie d'abord la plus utilisée est la voie postérieure. Les résultats fonctionnels ont été évalués, après un recul de 3 à 8 ans, selon la cotation de Merle d'Aubigné. Nous avons obtenu 90% de résultats satisfaisants. La comparaison de nos résultats à ceux de la littérature montre que le résultat des traitements orthopédiques et chirurgicaux dépend essentiellement du type de fracture. Le pronostic à long terme reste imprévisible. La survenue des complications tardives telle que la nécrose céphalique et de l'arthrose reste toujours imprévisible, ce qui impose un suivi régulier et prolongé des patients. PMID:25722763

Revision of cemented hip arthroplasty using a hydroxyapatite-ceramic-coated femoral component.

PubMed

Raman, R; Kamath, R P; Parikh, A; Angus, P D

2005-08-01

We report the clinical and radiological outcome of 86 revisions of cemented hip arthroplasties using JRI-Furlong hydroxyapatite-ceramic-coated acetabular and femoral components. The acetabular component was revised in 62 hips and the femoral component in all hips. The mean follow-up was 12.6 years and no patient was lost to follow-up. The mean age of the patients was 71.2 years. The mean Harris hip and Oxford scores were 82 (59 to 96) and 23.4 (14 to 40), respectively. The mean Charnley modification of the Merle d'Aubigné and Postel score was 5 (3 to 6) for pain, 4.9 (3 to 6) for movement and 4.4 (3 to 6) for mobility. Migration of the acetabular component was seen in two hips and the mean acetabular inclination was 42.6 degrees. The mean linear polyethylene wear was 0.05 mm/year. The mean subsidence of the femoral component was 1.9 mm and stress shielding was seen in 23 (28%) with bony ingrowth in 76 (94%). Heterotopic ossification was seen in 12 hips (15%). There were three re-revisions, two for deep sepsis and one for recurrent dislocation and there were no re-revisions for aseptic loosening. The mean EuroQol EQ-5D description scores and health thermometer scores were 0.69 (0.51 to 0.89) and 79 (54 to 95), respectively. With an end-point of definite or probable loosening, the probability of survival at 12 years was 93.9% and 95.6% for the acetabular and femoral components, respectively. Overall survival at 12 years, with removal or further revision of either component for any reason as the end-point, was 92.3%. Our study supports the continued use of this arthroplasty and documents the durability of hydroxyapatite-ceramic-coated components.

Public health impacts of excess NOx emissions from Volkswagen diesel passenger vehicles in Germany

NASA Astrophysics Data System (ADS)

Chossière, Guillaume P.; Malina, Robert; Ashok, Akshay; Dedoussi, Irene C.; Eastham, Sebastian D.; Speth, Raymond L.; Barrett, Steven R. H.

2017-03-01

In September 2015, the Volkswagen Group (VW) admitted the use of ‘defeat devices’ designed to lower emissions measured during VW vehicle testing for regulatory purposes. Globally, 11 million cars sold between 2008 and 2015 are affected, including about 2.6 million in Germany. On-road emissions tests have yielded mean on-road NOx emissions for these cars of 0.85 g km-1, over four times the applicable European limit of 0.18 g km-1. This study estimates the human health impacts and costs associated with excess emissions from VW cars driven in Germany. A distribution of on-road emissions factors is derived from existing measurements and combined with sales data and a vehicle fleet model to estimate total excess NOx emissions. These emissions are distributed on a 25 by 28 km grid covering Europe, using the German Federal Environmental Protection Agency’s (UBA) estimate of the spatial distribution of NOx emissions from passenger cars in Germany. We use the GEOS-Chem chemistry-transport model to predict the corresponding increase in population exposure to fine particulate matter and ozone in the European Union, Switzerland, and Norway, and a set of concentration-response functions to estimate mortality outcomes in terms of early deaths and of life-years lost. Integrated over the sales period (2008-2015), we estimate median mortality impacts from VW excess emissions in Germany to be 1200 premature deaths in Europe, corresponding to 13 000 life-years lost and 1.9 billion EUR in costs associated with life-years lost. Approximately 60% of mortality costs occur outside Germany. For the current fleet, we estimate that if on-road emissions for all affected VW vehicles in Germany are reduced to the applicable European emission standard by the end of 2017, this would avert 29 000 life-years lost and 4.1 billion 2015 EUR in health costs (median estimates) relative to a counterfactual case with no recall.

Suppressor of K+ transport growth defect 1 (SKD1) interacts with RING-type ubiquitin ligase and sucrose non-fermenting 1-related protein kinase (SnRK1) in the halophyte ice plant

PubMed Central

Chiang, Chih-Pin; Li, Chang-Hua; Jou, Yingtzy; Chen, Yu-Chan; Lin, Ya-Chung; Yang, Fang-Yu; Huang, Nu-Chuan; Yen, Hungchen Emilie

2013-01-01

SKD1 (suppressor of K+ transport growth defect 1) is an AAA-type ATPase that functions as a molecular motor. It was previously shown that SKD1 accumulates in epidermal bladder cells of the halophyte Mesembryanthemum crystallinum. SKD1 knock-down Arabidopsis mutants showed an imbalanced Na+/K+ ratio under salt stress. Two enzymes involved in protein post-translational modifications that physically interacted with McSKD1 were identified. McCPN1 (copine 1), a RING-type ubiquitin ligase, has an N-terminal myristoylation site that links to the plasma membrane, a central copine domain that interacts with McSKD1, and a C-terminal RING domain that catalyses protein ubiquitination. In vitro ubiquitination assay demonstrated that McCPN1 was capable of mediating ubiquitination of McSKD1. McSnRK1 (sucrose non-fermenting 1-related protein kinase) is a Ser/Thr protein kinase that contains an N-terminal STKc catalytic domain to phosphorylate McSKD1, and C-terminal UBA and KA1 domains to interact with McSKD1. The transcript and protein levels of McSnRK1 increased as NaCl concentrations increased. The formation of an SKD1–SnRK1–CPN1 ternary complex was demonstrated by yeast three-hybrid and bimolecular fluorescence complementation. It was found that McSKD1 preferentially interacts with McSnRK1 in the cytosol, and salt induced the re-distribution of McSKD1 and McSnRK1 towards the plasma membrane via the microtubule cytoskeleton and subsequently interacted with RING-type E3 McCPN1. The potential effects of ubiquitination and phosphorylation on McSKD1, such as changes in the ATPase activity and cellular localization, and how they relate to the functions of SKD1 in the maintenance of Na+/K+ homeostasis under salt stress, are discussed. PMID:23580756

New human biomonitoring methods for chemicals of concern-the German approach to enhance relevance.

PubMed

Kolossa-Gehring, Marike; Fiddicke, Ulrike; Leng, Gabriele; Angerer, Jürgen; Wolz, Birgit

2017-03-01

In Germany strong efforts have been made within the last years to develop new methods for human biomonitoring (HBM). The German Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the German Chemical Industry Association e. V. (VCI) cooperate since 2010 to increase the knowledge on the internal exposure of the general population to chemicals. The projects aim is to promote human biomonitoring by developing new analytical methods Key partner of the cooperation is the German Environment Agency (UBA) which has been entrusted with the scientific coordination. Another key partner is the "HBM Expert Panel" which each year puts together a list of chemicals of interest to the project from which the Steering Committee of the project choses up to five substances for which method development will be started. Emphasis is placed on substances with either a potential health relevance or on substances to which the general population is potentially exposed to a considerable extent. The HBM Expert Panel also advises on method development. Once a method is developed, it is usually first applied to about 40 non-occupationally exposed individuals. A next step is applying the methods to different samples. Either, if the time trend is of major interest, to samples from the German Environmental Specimen Bank, or, in case exposure sources and distribution of exposure levels in the general population are the focus, the new methods are applied to samples from children and adolescents from the population representative 5th German Environmental Survey (GerES V). Results are expected in late 2018. This article describes the challenges faced during method development and solutions found. An overview presents the 34 selected substances, the 14 methods developed and the 7 HBM-I values derived in the period from 2010 to mid 2016. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Multiple UBXN family members inhibit retrovirus and lentivirus production and canonical NFκΒ signaling by stabilizing IκBα.

PubMed

Hu, Yani; O'Boyle, Kaitlin; Auer, Jim; Raju, Sagar; You, Fuping; Wang, Penghua; Fikrig, Erol; Sutton, Richard E

2017-02-01

UBXN proteins likely participate in the global regulation of protein turnover, and we have shown that UBXN1 interferes with RIG-I-like receptor (RLR) signaling by interacting with MAVS and impeding its downstream effector functions. Here we demonstrate that over-expression of multiple UBXN family members decreased lentivirus and retrovirus production by several orders-of-magnitude in single cycle assays, at the level of long terminal repeat-driven transcription, and three family members, UBXN1, N9, and N11 blocked the canonical NFκB pathway by binding to Cullin1 (Cul1), inhibiting IκBα degradation. Multiple regions of UBXN1, including its UBA domain, were critical for its activity. Elimination of UBXN1 resulted in early murine embryonic lethality. shRNA-mediated knockdown of UBXN1 enhanced human immunodeficiency virus type 1 (HIV) production up to 10-fold in single cycle assays. In primary human fibroblasts, knockdown of UBXN1 caused prolonged degradation of IκBα and enhanced NFκB signaling, which was also observed after CRISPR-mediated knockout of UBXN1 in mouse embryo fibroblasts. Knockout of UBXN1 significantly up- and down-regulated hundreds of genes, notably those of several cell adhesion and immune signaling pathways. Reduction in UBXN1 gene expression in Jurkat T cells latently infected with HIV resulted in enhanced HIV gene expression, consistent with the role of UBXN1 in modulating the NFκB pathway. Based upon co-immunoprecipitation studies with host factors known to bind Cul1, models are presented as to how UBXN1 could be inhibiting Cul1 activity. The ability of UBXN1 and other family members to negatively regulate the NFκB pathway may be important for dampening the host immune response in disease processes and also re-activating quiescent HIV from latent viral reservoirs in chronically infected individuals.

Suppressor of K+ transport growth defect 1 (SKD1) interacts with RING-type ubiquitin ligase and sucrose non-fermenting 1-related protein kinase (SnRK1) in the halophyte ice plant.

PubMed

Chiang, Chih-Pin; Li, Chang-Hua; Jou, Yingtzy; Chen, Yu-Chan; Lin, Ya-Chung; Yang, Fang-Yu; Huang, Nu-Chuan; Yen, Hungchen Emilie

2013-05-01

SKD1 (suppressor of K+ transport growth defect 1) is an AAA-type ATPase that functions as a molecular motor. It was previously shown that SKD1 accumulates in epidermal bladder cells of the halophyte Mesembryanthemum crystallinum. SKD1 knock-down Arabidopsis mutants showed an imbalanced Na+/K+ ratio under salt stress. Two enzymes involved in protein post-translational modifications that physically interacted with McSKD1 were identified. McCPN1 (copine 1), a RING-type ubiquitin ligase, has an N-terminal myristoylation site that links to the plasma membrane, a central copine domain that interacts with McSKD1, and a C-terminal RING domain that catalyses protein ubiquitination. In vitro ubiquitination assay demonstrated that McCPN1 was capable of mediating ubiquitination of McSKD1. McSnRK1 (sucrose non-fermenting 1-related protein kinase) is a Ser/Thr protein kinase that contains an N-terminal STKc catalytic domain to phosphorylate McSKD1, and C-terminal UBA and KA1 domains to interact with McSKD1. The transcript and protein levels of McSnRK1 increased as NaCl concentrations increased. The formation of an SKD1-SnRK1-CPN1 ternary complex was demonstrated by yeast three-hybrid and bimolecular fluorescence complementation. It was found that McSKD1 preferentially interacts with McSnRK1 in the cytosol, and salt induced the re-distribution of McSKD1 and McSnRK1 towards the plasma membrane via the microtubule cytoskeleton and subsequently interacted with RING-type E3 McCPN1. The potential effects of ubiquitination and phosphorylation on McSKD1, such as changes in the ATPase activity and cellular localization, and how they relate to the functions of SKD1 in the maintenance of Na+/K+ homeostasis under salt stress, are discussed.

SVHC in imported articles: REACH authorisation requirement justified under WTO rules.

PubMed

Schenten, Julian; Führ, Martin

2016-01-01

The purpose of the REACH Regulation is to ensure a high level of protection of human health and the environment as well as the free circulation of substances on the internal market while enhancing competitiveness and innovation. To this end, REACH introduces, among other instruments, the authorisation regime for substances of very high concern (SVHC) that are listed on Annex XIV of the regulation. After expiration of the transitional period for each Annex XIV-SVHC, articles, such as most products of daily use, produced in the European Economic Area (EEA) may not contain such substances unless an authorisation was granted for the specific use or this use falls within the scope of an exemption from the authorisation requirement. The authorisation scheme does, however, only apply to SVHC used in the EEA. As a consequence, REACH does not regulate SVHC entering the European market as part of imported articles which burden human health and the environment. Moreover, from an economic perspective, domestic articles are subject to stricter requirements than those which are produced abroad, putting actors from within the EEA at competitive disadvantage and thus impeding the intention of REACH to enhance competitiveness and innovation. One option to close this regulatory gap could be to extend the authorisation requirement to SVHC present in imported articles. A legal appraisal on behalf of the German Environment Agency (UBA) assesses whether such option would be in accordance with the specifications of WTO world trade law. It concludes that, measured by the standards of the WTO dispute settlement practice, such an extended authorisation scheme would neither violate the principles of national treatment and most-favoured nation treatment. Also, such regulation would not constitute an unnecessary obstacle to trade, since the extended authorisation requirement would pursue a legitimate objective covered by the regulatory autonomy of the EU and, furthermore, the regulation would not be more trade-restrictive than necessary. The contribution at hand summarises the main findings while taking into account first reactions to the legal appraisal.

Involvement of kinase PKC-zeta in the p62/p62(P392L)-driven activation of NF-κB in human osteoclasts.

PubMed

Chamoux, Estelle; McManus, Stephen; Laberge, Gino; Bisson, Martine; Roux, Sophie

2013-03-01

Mutations of the gene encoding sequestosome1 (SQSTM1/p62), clustering in or near the UBA domain, have been described in Paget's disease of bone (PDB); among these the P392L substitution is the most prevalent. Protein p62 mediates several cell functions, including the control of NF-κB signaling, and autophagy. This scaffolding protein interacts with atypical PKCζ in the RANKL-induced signaling complex. We have previously shown that osteoclasts (OCs) overexpressing the p62(P392L) variant were in a constitutively activated state, presenting activated kinase p-PKCζ/λ and activated NF-κB prior to RANKL stimulation. In the present study, we investigated the relationships between PKCζ and NF-κB activation in human OCs transfected with p62 variants. We showed that PKCζ and p-PKCζ/λ co-localize with p62, and that PKCζ is involved in the RANKL-induced NF-κB activation and in the RANKL-independent activation of NF-κB observed in p62(P392L)-transfected cells. We also observed a basal and RANKL-induced increase in IκBα levels in the presence of the p62(P392L) mutation that contrasted with the NF-κB activation. In this study we propose that PKCζ plays a role in the activation of NF-κB by acting as a p65 (RelA) kinase at Ser(536), independently of IκBα; this alternative pathway could be used preferentially in the presence of the p62(P392L) mutation, which may hinder the ubiquitin-proteasome pathway. Overall, our results highlight the importance of p62-associated PKCζ in the overactive state of pagetic OCs and in the activation of NF-κB, particularly in the presence of the p62(P392L) mutation. Copyright © 2012 Elsevier B.V. All rights reserved.

[Substance monograph on bisphenol A (BPA) - reference and human biomonitoring (HBM) values for BPA in urine. Opinion of the Human Biomonitoring Commission of the German Federal Environment Agency (UBA)].

PubMed

2012-09-01

Bisphenol A (BPA) is used for the production of polycarbonates and synthetic resins. Many of the items that contain BPA, for example polycarbonate bottles and coated cans, are commodities from which BPA can migrate into food and drinks, resulting in ubiquitous exposure of the population. Numerous animal studies and in vitro tests have shown that BPA acts as an "endocrine disruptor". Because of the still incomplete understanding of the complex and contradictory effects of BPA at doses below the NOAEL, the toxicological significance of recent findings is uncertain. The German HBM Commission takes notice that the risk assessment is currently in flux and that in the EU and other countries precautionary bans on BPA have been introduced. In the light of the extensive and growing body of literature, the Commission does not see itself in a position to resolve this controversy, nor to answer the question of the relevance of observed effects of low BPA doses on human health. The Commission has derived reference values (RV95) and TDI-based HBM I values for total BPA in urine. The RV95 values are 30 μg/l for 3-5 year olds, 15 μg/l for 6-14 year olds, and 7 μg/l for 20-29 year olds. The HBM I value for children is 1.5 mg/l and 2.5 mg/l for adults, respectively. The Commission emphasizes that the HBM values will require immediate adjustment should the current TDI of 0.05 mg/kg bw/day be changed. For the practical application of HBM, the Commission recommends an assessment based on the RV95. Confirmed exceedance of the RV95 by repeat measurements should prompt a search for the possible source(s), following the ALARA principle.

Human Papillomavirus Type 18 E6 and E7 Genes Integrate into Human Hepatoma Derived Cell Line Hep G2

PubMed Central

Ma, Tianzhong; Su, Zhongjing; Chen, Ling; Liu, Shuyan; Zhu, Ningxia; Wen, Lifeng; Yuan, Yan; Lv, Leili; Chen, Xiancai; Huang, Jianmin; Chen, Haibin

2012-01-01

Background and Objectives Human papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well. Methods We applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples. Results Hep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma. Conclusion Our investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study. PMID:22655088

Does Participation in Sports Affect Osteoarthritic Progression After Periacetabular Osteotomy?

PubMed

Hara, Daisuke; Hamai, Satoshi; Fukushi, Jun-Ichi; Kawaguchi, Ken-Ichi; Motomura, Goro; Ikemura, Satoshi; Komiyama, Keisuke; Nakashima, Yasuharu

2017-09-01

Periacetabular osteotomy (PAO) is an effective treatment for symptomatic acetabular dysplasia. However, whether postoperative participation in sports leads to progression of the Kellgren-Lawrence (KL) grade of osteoarthritis (OA) in these patients is unclear. To investigate (1) participation in sports before and after PAO and (2) whether postoperative participation in sports leads to progression of the KL grade. Case-control study; Level of evidence, 3. The authors retrospectively reviewed data on 161 patients (183 hips) who underwent PAO for symptomatic acetabular dysplasia with preoperative KL grade 1 or 2 between 1998 and 2011. The mean age at the time of surgery was 42.0 ± 10.9 years (range, 12-64 years), and the mean follow-up duration was 100 months (range, 13-180 months). Data included participation in sports, the University of California, Los Angeles (UCLA) activity scale score, age at the time of surgery, body mass index, follow-up duration, history of treatment for developmental hip dislocations, Merle d'Aubigné-Postel score, Oxford Hip Score, center-edge angle, and KL grade. Univariate and multivariate analyses were applied to determine which factors were associated with progression to KL grade 3 or 4 after PAO. The number of patients who participated in sports significantly increased from 50 (31.1%) preoperatively to 89 (55.3%) postoperatively. The mean UCLA score significantly increased from 4.7 ± 2.1 preoperatively to 5.5 ± 2.0 postoperatively. The KL grade progressed to grade 3 or 4 in 16 hips, including 4 hips that underwent conversion to total hip arthroplasty. No significant differences were found in postoperative participation in sports (89 hips [53.3%] vs 11 hips [68.8%], respectively; P = .24) and the UCLA score (5.6 ± 2.0 vs 5.1 ± 2.0, respectively; P = .30) between hips with KL grade 1 or 2 and KL grade 3 or 4. A multivariate analysis revealed that no factors, including postoperative participation in sports, were significantly associated with progression to KL grade 3 or 4. Postoperative participation in sports after PAO did not significantly and negatively influence progression of the KL grade at midterm follow-up.

Can cemented dual-mobility cups be used without a reinforcement device in cases of mild acetabular bone stock alteration in total hip arthroplasty?

PubMed

Haen, T X; Lonjon, G; Vandenbussche, E

2015-12-01

Cemented versions of dual-mobility cups (DMCs), helpful in cases of bone stock alteration, are usually used in association with a reinforcement device. To simplify the intervention in elderly subjects or those with a poor bone stock, the cups can be cemented directly into the bone, but the long-term result remains uncertain. We conducted a retrospective study in this population so as to: (1) assess whether cemented fixation of a DMC without a reinforcement device leads to a higher loosening rate, (2) confirm its efficacy in preventing dislocations in subjects at high risk of instability, and (3) measure the functional results. Cemented fixation of a DMC is reliable in cases of moderate alteration of bone stock. Sixty-four patients (66 hips) undergoing implantation of a cemented DMC (Saturne™) without a reinforcement device were included in this single-center retrospective study. Their mean age was 79.8 years (range, 40-95 years). The indications varied: hip osteoarthritis (30.3%), prosthesis revision (44.0%), and trauma (25.8%). The patients were evaluated radiologically and clinically at follow-up. The main evaluation criterion was the revision rate for aseptic loosening. Dislocations, the infection rate, and the Postel Merle d'Aubigné (PMA) score were noted. At the mean follow-up of 4.2 years, three (4.6%) patients had been lost to follow-up and 22 (33.3%) had died. There was one case of aseptic loosening (1.5%). Cup survival was 98% at 5 years (95%CI [94-100]). There were no dislocations. There was one revision for infection. The mean PMA score was 15.5 (range, 9-18). The frequency of acetabular loosening was comparable to the frequency in cemented DMCs with a reinforcement device. A cemented DMC without a reinforcement device is possible and is a simple and viable option when there is moderate bone stock alteration. IV, retrospective cohort study. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Fresh osteochondral allograft transplantation for isolated patellar cartilage injury.

PubMed

Gracitelli, Guilherme C; Meric, Gokhan; Pulido, Pamela A; Görtz, Simon; De Young, Allison J; Bugbee, William D

2015-04-01

The treatment of patellofemoral cartilage injuries can be challenging. Osteochondral allograft (OCA) transplantation has been used as a treatment option for a range of cartilage disorders. To evaluate functional outcomes and survivorship of the grafts among patients who underwent OCA for patellar cartilage injuries. Case series; Level of evidence, 4. An institutional review board-approved OCA database was used to identify 27 patients (28 knees) who underwent isolated OCA transplantation of the patella between 1983 and 2010. All patients had a minimum 2-year follow-up. The mean age of the patients was 33.7 years (range, 14-64 years); 54% were female. Twenty-six (92.9%) knees had previous surgery (mean, 3.2 procedures; range, 1-10 procedures). The mean allograft area was 10.1 cm(2) (range, 4.0-18.0 cm(2)). Patients returned for clinical evaluation or were contacted via telephone for follow-up. The number and type of reoperations were assessed. Any reoperation resulting in removal of the allograft was considered a failure of the OCA transplantation. Patients were evaluated pre- and postoperatively using the modified Merle d'Aubigné-Postel (18-point) scale, the International Knee Documentation Committee (IKDC) pain, function, and total scores, and the Knee Society function (KS-F) score. Patient satisfaction was assessed at latest follow-up. Seventeen of the 28 knees (60.7%) had further surgery after the OCA transplantation; 8 of the 28 knees (28.6%) were considered OCA failures (4 conversions to total knee arthroplasty, 2 conversions to patellofemoral knee arthroplasty, 1 revision OCA, 1 patellectomy). Patellar allografting survivorship was 78.1% at 5 and 10 years and 55.8% at 15 years. Among the 20 knees (71.4%) with grafts in situ, the mean follow-up duration was 9.7 years (range, 1.8-30.1 years). Pain and function improved from the preoperative visit to latest follow-up, and 89% of patients were extremely satisfied or satisfied with the results of the OCA transplantation. OCA transplantation was successful as a salvage treatment procedure for cartilage injuries of the patella. © 2015 The Author(s).

Perspective of an Artist Inspired by Physics

NASA Astrophysics Data System (ADS)

Sanborn, Jim

2010-02-01

Using digital images and video I will be presenting thirty years of my science based artwork. Beginning in the late 1970's my gallery and museum installations used lodestones and suspended compasses to reveal the earths' magnetic field. Through the 1980's my work included these compass installations and geologically inspired tableaux that had one thing in common, they were designed to expose the invisible forces of nature. Tectonics, the Coriolis force, and magnetism were among the subjects of study. In 1988, on the basis of my work with invisible forces, I was selected for a commission from the General Services Administration for the new Central Intelligence Agency headquarters in Langley Virginia. This work titled Kryptos included a large cryptographic component that remains undeciphered twenty years after its installation. In the 1990's Kryptos inspired several of my museum and gallery installations using cryptography and secrecy as their main themes. From 1995-1998 I completed a series of large format projections on the landscape in the western US and Ireland. These projections and the resulting series of photographs emulated the 19th century cartographers hired by the United States Government to map the western landscape. In 1998 I began my project titled Atomic Time. This installation shown for the first time in 2004 at the Corcoran Gallery in Washington DC, then again in the Gwangju Biennale in South Korea was a recreation of the 1944 Manhattan Project laboratory that built the first Atomic Bomb. This installation used original equipment and prototypes from the Los Alamos Lab and was an extremely accurate representation of the laboratory and the first nuclear bomb called the ``Trinity Device.'' I began my current project Terrestrial Physics in 2005. This installation to be shown in June 2010 at the Museum of Contemporary Art in Denver is a recreation of the large particle accelerator and the experiment that fissioned Uranium in 1939 at the Carnegie Institution in Washington DC. This was the first time uranium had been fissioned using a particle accelerator and it was demonstrated for an audience including, Enrico Fermi, Niels Bohr and Merle Tuve. )

Ubiquitin-Like Proteasome System Represents a Eukaryotic-Like Pathway for Targeted Proteolysis in Archaea

DOE PAGES

Fu, Xian; Liu, Rui; Sanchez, Iona; ...

2016-05-17

The molecular mechanisms of targeted proteolysis in archaea are poorly understood, yet they may have deep evolutionary roots shared with the ubiquitin-proteasome system of eukaryotic cells. Here, we demonstrate in archaea that TBP2, a TATA-binding protein (TBP) modified by ubiquitin-like isopeptide bonds, is phosphorylated and targeted for degradation by proteasomes. Rapid turnover of TBP2 required the functions of UbaA (the E1/MoeB/ThiF homolog of archaea), AAA ATPases (Cdc48/p97 and Rpt types), a type 2 JAB1/MPN/MOV34 metalloenzyme (JAMM/MPN+) homolog (JAMM2), and 20S proteasomes. The ubiquitin-like protein modifier small archaeal modifier protein 2 (SAMP2) stimulated the degradation of TBP2, but SAMP2 itself wasmore » not degraded. Analysis of the TBP2 fractions that were not modified by ubiquitin-like linkages revealed that TBP2 had multiple N termini, including Met1-Ser2, Ser2, and Met1-Ser2(p) [where (p) represents phosphorylation]. The evidence suggested that the Met1-Ser2(p) form accumulated in cells that were unable to degrade TBP2. We propose a model in archaea in which the attachment of ubiquitin-like tags can target proteins for degradation by proteasomes and be controlled by N-terminal degrons. In support of a proteolytic mechanism that is energy dependent and recycles the ubiquitin-like protein tags, we find that a network of AAA ATPases and a JAMM/MPN+ metalloprotease are required, in addition to 20S proteasomes, for controlled intracellular proteolysis. IMPORTANCEThis study advances the fundamental knowledge of signal-guided proteolysis in archaea and sheds light on components that are related to the ubiquitin-proteasome system of eukaryotes. In archaea, the ubiquitin-like proteasome system is found to require function of an E1/MoeB/ThiF homolog, a type 2 JAMM/MPN+ metalloprotease, and a network of AAA ATPases for the targeted destruction of proteins. We provide evidence that the attachment of the ubiquitin-like protein is controlled by an N-terminal degron and stimulates proteasome-mediated proteolysis.« less

BioMig--A Method to Evaluate the Potential Release of Compounds from and the Formation of Biofilms on Polymeric Materials in Contact with Drinking Water.

PubMed

Wen, Gang; Kötzsch, Stefan; Vital, Marius; Egli, Thomas; Ma, Jun

2015-10-06

In contact with water, polymeric materials (plastics) release compounds that can support suspended microbial growth and/or biofilm formation. The different methods presently used in the European Union to test plastics take 7-16 weeks to obtain a result. In industry, this delays material and product development as well as quality testing. Therefore, we developed a method package (BioMig) that allows testing of plastic materials with high reproducibility in 2 weeks for their potential biofilm (or biomass) formation and release of carbonaceous migration products when in contact with water. BioMig consists of (i) an extended migration potential test (seven times for 24 h at 60 °C), based on the European norm EN 12873-1 and the German UBA (Umweltbundesamt) guideline, and (ii) a biomass formation potential (BFP) test (14 days at 30 °C), which is a modified version of the Dutch biofilm production potential test. In the migration potential test, the amount of carbon released into water by the specimen is quantified by monitoring total and assimilable organic carbon over time; furthermore, the modular design of the test also allows one to assess additional parameters such as pathogen growth potential on the migration water or toxic effects on microbial growth. Flow cytometry (FCM)-based total cell counting (TCC) is used to quantify microbial growth in suspension and on surfaces after removal with mild sonication without affecting cell integrity. The BFP test allows one to determine both the planktonic (pBFP) and the sessile (sBFP) cell fractions. The sBFP consists of surface-attached cells after removal (>90% efficiency). Results for four standard test materials (PE-Xa, PE-Xc, EPDM 2%, and EPDM 20%), plus positive (PVC-P) and negative (glass) controls are presented. FCM-based TCC demonstrates that the release of growth-supporting carbon and proliferation of surface-attached cells stops increasing and stabilizes after 14 days of incubation; this allows for faster assessment of growth-supporting properties of plastics with BioMig compared to established tests.

Tum1 is involved in the metabolism of sterol esters in Saccharomyces cerevisiae.

PubMed

Uršič, Katja; Ogrizović, Mojca; Kordiš, Dušan; Natter, Klaus; Petrovič, Uroš

2017-08-22

The only hitherto known biological role of yeast Saccharomyces cerevisiae Tum1 protein is in the tRNA thiolation pathway. The mammalian homologue of the yeast TUM1 gene, the thiosulfate sulfurtransferase (a.k.a. rhodanese) Tst, has been proposed as an obesity-resistance and antidiabetic gene. To assess the role of Tum1 in cell metabolism and the putative functional connection between lipid metabolism and tRNA modification, we analysed evolutionary conservation of the rhodanese protein superfamily, investigated the role of Tum1 in lipid metabolism, and examined the phenotype of yeast strains expressing the mouse homologue of Tum1, TST. We analysed evolutionary relationships in the rhodanese superfamily and established that its members are widespread in bacteria, archaea and in all major eukaryotic groups. We found that the amount of sterol esters was significantly higher in the deletion strain tum1Δ than in the wild-type strain. Expression of the mouse TST protein in the deletion strain did not rescue this phenotype. Moreover, although Tum1 deficiency in the thiolation pathway was complemented by re-introducing TUM1, it was not complemented by the introduction of the mouse homologue Tst. We further showed that the tRNA thiolation pathway is not involved in the regulation of sterol ester content in S. cerevisiae, as overexpression of the tE UUC , tK UUU and tQ UUG tRNAs did not rescue the lipid phenotype in the tum1Δ deletion strain, and, additionally, deletion of the key gene for the tRNA thiolation pathway, UBA4, did not affect sterol ester content. The rhodanese superfamily of proteins is widespread in all organisms, and yeast TUM1 is a bona fide orthologue of mammalian Tst thiosulfate sulfurtransferase gene. However, the mouse TST protein cannot functionally replace yeast Tum1 protein, neither in its lipid metabolism-related function, nor in the tRNA thiolation pathway. We show here that Tum1 protein is involved in lipid metabolism by decreasing the sterol ester content in yeast cells, and that this function of Tum1 is not exerted through the tRNA thiolation pathway, but through another, currently unknown pathway.

Analogue modelling of strike-slip fault propagation across a rheological/morphological crustal anisotropy: implications for the morphotectonic evolution of the Gloria Fault - Tore Madeira Rise area in NE Atlantic.

NASA Astrophysics Data System (ADS)

Tomás, Ricardo; Rosas, Filipe M.; Duarte, João C.; Terrinha, Pedro; Kullberg, Maria C.; Almeida, Jaime; Barata, Frederico; Carvalho, Bruno; Almeida, Pedro

2015-04-01

The Gloria Fault (GF) marks the E-W dextral transcurrent plate boundary between Eurasia and Africa in NE Atlantic, displaying complying high magnitude (historical and instrumental) seismic activity (e.g. M=7.1 in 1939 and M=8.4 in 1941, Bufforn et al., 1988), and cutting across a NNE-SSW 1000 km long bathymetric ridge: the so called Tore-Madeira Rise - TMR (rising in average 3km above the abyssal plain). The precise origin and tectono-magmatic evolution of the TMR is still not fully understood, although reported wide-angle refraction data points to a rheological configuration comprising an isostatically compensated thickened oceanic crust, possibly formed during a period of high accretion in the Mid-Atlantic Ridge (Pierce and Barton, 1991). Widespread evidence for volcanic activity has also been recognized, spanning from late Cretaceous to Present (Geldmacher et al. 2006, Merle et al. 2009), noticeably with the most recent volcanism (~500 Ky) occurring as tectonically aligned volcanic plugs, distributed along the E-W tectonic trend of the GF-related structures. To better understand the complex interference at play in this key area between the tectonic structures (essentially determined by the Gloria Fault system), the present and past magmatic activity and the resulting seafloor morphology, a series of dynamically scaled analogue modelling experiments have been conceived and carried out. The main focus of this experimental work was to decipher the potential influence of a rheological vs. morphological anisotropy (accounting for the TMR) on the lateral propagation of a major right-lateral strike-slip fault (representing the GF). The preliminary comparison of the obtained experimental results with the natural morphotectonic pattern in the study area reveals, not only a strong tectonic control of the ongoing volcanism, manifested by the observed preferred directions of aligned volcanic plugs, but also a so far unsuspected deflection/distributed pattern of several faults, and other GF-related structures, here interpreted as resulting from the specific rheological constrains (e.g. crustal soft anomalies) underlying the distributed volcanic activity throughout the TMR. Acknowledgments This work was sponsored by the Fundação para a Ciência e a Tecnologia (FCT) through project MODELINK EXPL/GEO-GEO/0714/2013.

[Application of three-dimensional printing personalized acetabular wing-plate in treatment of complex acetabular fractures via lateral-rectus approach].

PubMed

Mai, J G; Gu, C; Lin, X Z; Li, T; Huang, W Q; Wang, H; Tan, X Y; Lin, H; Wang, Y M; Yang, Y Q; Jin, D D; Fan, S C

2017-03-01

Objective: To investigate reduction and fixation of complex acetabular fractures using three-dimensional (3D) printing technique and personalized acetabular wing-plate via lateral-rectus approach. Methods: From March to July 2016, 8 patients with complex acetabular fractures were surgically managed through 3D printing personalized acetabular wing-plate via lateral-rectus approach at Department of Orthopedics, the Third Affiliated Hospital of Southern Medical University. There were 4 male patients and 4 female patients, with an average age of 57 years (ranging from 31 to 76 years). According to Letournel-Judet classification, there were 2 anterior+ posterior hemitransverse fractures and 6 both-column fractures, without posterior wall fracture or contralateral pelvic fracture. The CT data files of acetabular fracture were imported into the computer and 3D printing technique was used to print the fractures models after reduction by digital orthopedic technique. The acetabular wing-plate was designed and printed with titanium. All fractures were treated via the lateral-rectus approach in a horizontal position after general anesthesia. The anterior column and the quadrilateral surface fractures were fixed by 3D printing personalized acetabular wing-plate, and the posterior column fractures were reduction and fixed by antegrade lag screws under direct vision. Results: All the 8 cases underwent the operation successfully. Postoperative X-ray and CT examination showed excellent or good reduction of anterior and posterior column, without any operation complications. Only 1 case with 75 years old was found screw loosening in the pubic bone with osteoporosis after 1 month's follow-up, who didn't accept any treatment because the patient didn't feel discomfort. According to the Matta radiological evaluation, the reduction of the acetabular fracture was rated as excellent in 3 cases, good in 4 cases and fair in 1 case. All patients were followed up for 3 to 6 months and all patients had achieved bone union. According to the modified Merle D'Aubigné and Postel scoring system, 5 cases were excellent, 2 cases were good, 1 case was fair. Conclusions: Surgical management of complex acetabular fracture via lateral-rectus approach combine with 3D printing personalized acetabular wing-plate can effectively improve reduction quality and fixation effect. It will be truly accurate, personalized and minimally invasive.

Le traitement chirurgical des fractures du cotyle: à propos de 22 cas

PubMed Central

Mahdane, Hicham; Elghazi, Amine; Shimi, Mohamed; Elibrahimi, Abdelhalim; Elmrini, Abdelmajid

2014-01-01

Vingt deux patients présentant une fracture incongruente de l'acétabulum ont été opérés et revues avec un recul moyen de 2 ans. Le but de cette étude est d'analyser les résultats fonctionnels et radiologiques des fractures de l'acétabulum après traitement chirurgical. La population était constituée de 17 hommes et 5 femmes, avec un âge moyen de 42,5 ans. Les fractures de l'acétabulum étaient répertoriées selon la classification de Judet et Letournel: 11 fractures de la paroi postérieure, une fracture de la colonne postérieure, six fractures transversales, quatre fractures transversales associées à une paroi postérieure, et une seule fracture de la colonne postérieure avec fracture de la paroi postérieure. Quatre patients présentaient des lésions associées du bassin, sept patients avaient une luxation postérieur de la hanche, deux une luxation centrale et deux avaient un traumatisme crânien associée. Deux voies d'abords ont été utilisées dans ce travail: la voie de Kocher Langenbeck (19 cas), et la voie de Dana Mears (4 cas). A partir du bilan radiologique initial (bassin face, ¾ alaire, ¾ obturateur et tomodensitomértie) on évaluer le déplacement, la congruence, tête/toit et tête/acétabulum ainsi que le degré de comminution. La qualité de réduction était évaluée selon les critères de Matta et les résultats fonctionnels selon la cotation de Merle D'Aubigné. Sur le Plan radiologique nous avons obtenu 56,52% de réduction anatomique, alors que sur le plan fonctionnel 78% patient avaient de bons et très bon résultats. Parmi les complications postopératoires, on a noté un seul cas d'infection cutanée superficielle, cinq ossifications héterotopiques. A distance un cas d'ostéonécrose aseptique de la tête fémorale et un cas de coxarthrose. PMID:25374628

High-impact sport after hip resurfacing: The Ironman triathlon.

PubMed

Girard, J; Lons, A; Pommepuy, T; Isida, R; Benad, K; Putman, S

2017-09-01

Returning to high-impact sport is an increasingly frequent functional demand following hip replacement. The literature, however, is sparse on the subject and nonexistent regarding triathlon. We therefore conducted a retrospective study of hip resurfacing in triathlon players, to determine: (1) whether it is possible to return to this kind of sport; (2) if so, whether it is possible to return to the same level; and (3) how a resurfaced hip behaves under these conditions. Hip resurfacing allows return to competition level in long-distance triathlon. A single-center single-operator retrospective study included patients undergoing hip resurfacing with the Conserve Plus implant inserted through a posterolateral approach, who had ceased long-distance triathlon practice due to osteoarthritis of the hip. Fifty-one of the 1688 patients undergoing resurfacing during the inclusion period were long-distance triathlon players. The series comprised 48 patients: 51 implants; 43 male, 5 female; mean age, 44.8 years (range, 28.2-58.9 years). At a mean 4.7 years' follow-up (range, 2.2-7.6 years), all clinical scores showed significant improvement; Merle d'Aubigné and Harris scores rose respectively from 12.3 (5-16) and 42 (37-56) preoperatively to 17.5 (13-18) and 93.2 (73-100) (P<0.001). There were no cases of dislocation or implant revision. Forty-five patients returned to sport (94%). Rates of return to swimming, cycling and running were respectively 38/48 (79%), 41/48 (85%) and 33/48 (69%). Preoperatively, all patients had taken part in at least 1 competition: 29 with distance=70.3km and 19 with distance=140.6km. At follow-up, 28 patients had taken part in an Ironman competition: 21 with distance=70.3km and 7 with distance=140.6km. Mean competition performance did not differ between pre and postoperative periods. Return-to-sport rates were good following hip resurfacing. Non-impact sports (swimming, cycling) predominated postoperatively, whereas the rate of impact sport (running) diminished. Return to competition-level sport (extreme triathlon) was possible for 28/48 patients (58%). Implant survival seemed unaffected by this high-impact sports activity at a mean 4.7 years' follow-up. IV, retrospective, non-controlled. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Outcomes and prognostic factors in revision hip arthroplasty for severe intra-pelvic cup protrusion: 246 cases.

PubMed

Epinette, J-A; Mertl, P; Combourieu, B; Goncalves, H; Blairon, A; Ehlinger, M; Tabutin, J

2015-10-01

The outcome of revision total hip arthroplasty (THA) for intra-pelvic cup protrusion is unclear. Hence, we conducted a large retrospective study to clarify the surgical strategy (hip lever arm and cup mechanical fixation) and the outcomes of reconstruction for severe intra-pelvic cup protrusion. We hypothesized that restoration of the anatomic hip centre in such acetabular revisions decreased the risk of recurrent loosening. The study included 246 THA procedures (in 220 patients), with a follow-up of 5.2 ± 4.9 years (1-24.2) after the index surgery. Bone loss was estimated using the SOFCOT classification (grade III or IV in 80% of cases) and the Paprosky classification (IIIA or IIIB in 58% of cases). Quality of the reconstruction was assessed on X-rays according to the correction of the protrusion and position of the hip centre of rotation. After a clinical follow-up of at least 5 years, with a mean of 9.9 ± 4.1 years (5-24 years), the mean Postel-Merle d'Aubigné score was 14.2 ± 3.1 and the mean Harris Hip Score was 78.0 ± 18.7. Cup protrusion was partially or completely corrected in every case and cup position was normal in 27 (11%) cases. The centre of rotation was within 10mm of the physiological position in 158 (64.2%) cases, acceptable in 77 (31.3%) cases, ascended in 9 (3.7%) cases, and worsened in 1 (0.4%) case. Revision for cup or cup and femoral failures was required in 24 (9.8%) cases. Cumulative survival rates with cup loosening as the endpoint were 88.5% after 5 years, 79.9% after 10 years, and 63.9% at last follow-up at 13.6 years. Our hypothesis that restoration of anatomic hip centre decreased the risk of recurrent loosening was not verified: success or failure in restoring the normal centre of rotation did not correlate significantly with final cup status. Recurrent aseptic loosening was the cause of failure in 9.8% of cases. Ensuring long-term effective mechanical stability had a greater impact on global outcomes than restoring an ideal centre of rotation. Copyright © 2015. Published by Elsevier Masson SAS.

The E3 ubiquitin ligase NEDD4 mediates cell migration signaling of EGFR in lung cancer cells.

PubMed

Shao, Genbao; Wang, Ranran; Sun, Aiqin; Wei, Jing; Peng, Ke; Dai, Qian; Yang, Wannian; Lin, Qiong

2018-02-19

EGFR-dependent cell migration plays an important role in lung cancer progression. Our previous study observed that the HECT E3 ubiquitin ligase NEDD4 is significantly correlated with tumor metastasis and required for migration and invasion signaling of EGFR in gastric cancer cells. However, how NEDD4 promotes the EGFR-dependent lung cancer cell migration is unknown. This study is to elucidate the mechanism by which NEDD4 mediates the EGFR lung cancer migration signaling. Lentiviral vector-loaded NEDD4 shRNA was used to deplete endogenous NEDD4 in lung cancer cell lines. Effects of the NEDD4 knockdown on the EGFR-dependent or independent lung cancer cell migration were determined using the wound-healing and transwell assays. Association of NEDD4 with activated EGFR was assayed by co-immunoprecipitation. Co-expression of NEDD4 with EGFR or PTEN was determined by immunohistochemical (IHC) staining in 63 lung adenocarcinoma tissue samples. Effects of NEDD4 ectopic expression or knockdown on PTEN ubiquitination and down-regulation, AKT activation and lysosomal secretion were examined using the GST-Uba pulldown assay, immunoblotting, immunofluorescent staining and a human cathepsin B ELISA assay respectively. The specific cathepsin B inhibitor CA-074Me was used for assessing the role of cathepsin B in lung cancer cell migration. Knockdown of NEDD4 significantly reduced EGF-stimulated cell migration in non-small cell lung carcinoma (NSCLC) cells. Co-immunoprecipitation assay found that NEDD4 is associated with EGFR complex upon EGF stimulation, and IHC staining indicates that NEDD4 is co-expressed with EGFR in lung adenocarcinoma tumor tissues, suggesting that NEDD4 might mediate lung cancer cell migration by interaction with the EGFR signaling complex. Interestingly, NEDD4 promotes the EGF-induced cathepsin B secretion, possibly through lysosomal exocytosis, as overexpression of the ligase-dead mutant of NEDD4 impedes lysosomal secretion, and knockdown of NEDD4 significantly reduced extracellular amount of cathepsin B induced by EGF. Consistent with the role of NEDD4, cathepsin B is pivotal for both basal and the EGF-stimulated lung cancer cell migration. Our studies propose a novel mechanism underlying the EGFR-promoted lung cancer cell migration that is mediated by NEDD4 through regulation of cathepsin B secretion. NEDD4 mediates the EGFR lung cancer cell migration signaling through promoting lysosomal secretion of cathepsin B.

Hermes Transposon Mutagenesis Shows [URE3] Prion Pathology Prevented by a Ubiquitin-Targeting Protein: Evidence for Carbon/Nitrogen Assimilation Cross-Talk and a Second Function for Ure2p in Saccharomyces cerevisiae.

PubMed

Edskes, Herman K; Mukhamedova, Maryam; Edskes, Bouke K; Wickner, Reed B

2018-05-16

[URE3] is an amyloid-based prion of Ure2p, a regulator of nitrogen catabolism. While most variants of the [URE3] prion are toxic, mild variants that only slightly slow growth are more widely studied. The existence of several anti-prion systems suggests that some components may be protecting cells from potential detrimental effects of mild [URE3] variants. Our extensive Hermes transposon mutagenesis showed that disruption of YLR352W dramatically slows growth of [URE3-1] strains. Ylr352wp is an F-box protein, directing selection of substrates for ubiquitination by a cullin-containing E- 3 ligase. For efficient ubiquitylation, cullin-dependent E 3 ubiquitin ligases must be NEDDylated, modified by a ubiquitin-related peptide called NEDD8 (Rub1p in yeast). Indeed, we find that disruption of NEDDylation-related genes, RUB1, ULA1, UBA3 and UBC12 is also counterselected in our screen. We find that like ylr352w Δ [URE3] strains, ylr352w Δ ure2 Δ strains do not grow on non-fermentable carbon sources. Overexpression of Hap4p, a transcription factor stimulating expression of mitochondrial proteins, or mutation of GLN1 , encoding glutamine synthetase, allow growth of ylr352w Δ [URE3] strains on glycerol media. Supplying proline as a nitrogen source shuts off the nitrogen catabolite repression (NCR) function of Ure2p, but does not slow growth of ylr352w Δ strains, suggesting a distinct function of Ure2p in carbon catabolism. Also, gln1 mutations impair NCR, but actually relieve the growth defect of ylr352w Δ [URE3] and ylr352w Δ ure2 Δ strains, again showing that loss of NCR is not producing the growth defect and suggesting Ure2p has another function. YLR352W largely protects cells from the deleterious effects of otherwise mild [URE3] variants, or of a ure2 mutation (the latter a rarer event), and we name it LUG1 (lets [URE3]/ ure2 grow). Copyright © 2018, Genetics.

The pineal gland: A model for adrenergic modulation of ubiquitin ligases.

PubMed

Vriend, Jerry; Liu, Wenjun; Reiter, Russel J

2017-01-01

A recent study of the pineal gland of the rat found that the expression of more than 3000 genes showed significant day/night variations (The Hartley dataset). The investigators of this report made available a supplemental table in which they tabulated the expression of many genes that they did not discuss, including those coding for components of the ubiquitin proteasome system. Herein we identify the genes of the ubiquitin proteasome system whose expression were significantly influenced by environmental lighting in the Hartley dataset, those that were stimulated by DBcAMP in pineal glands in culture, and those that were stimulated by norepinephrine. Using the Ubiquitin and Ubiquitin-like Conjugation Database (UUCA) we identified ubiquitin ligases and conjugases, and deubiquitinases in the Hartley dataset for the purpose of determining whether expression of genes of the ubiquitin proteasome pathway were significantly influenced by day/night variations and if these variations were regulated by autonomic innervation of the pineal gland from the superior cervical ganglia. In the Hartley experiments pineal glands groups of rats sacrificed during the day and groups sacrificed during the night were examined for gene expression. Additional groups of rats had their superior cervical ganglia removed surgically or surgically decentralized and the pineal glands likewise examined for gene expression. The genes with at least a 2-fold day/night significant difference in expression included genes for 5 ubiquitin conjugating enzymes, genes for 58 ubiquitin E3 ligases and genes for 6 deubiquitinases. A 35-fold day/night difference was noted in the expression of the gene Sik1, which codes for a protein containing both an ubiquitin binding domain (UBD) and an ubiquitin-associated (UBA) domain. Most of the significant differences in these genes were prevented by surgical removal, or disconnection, of the superior cervical ganglia, and most were responsive, in vitro, to treatment with a cyclic AMP analog, and norepinephrine. All previously described 24-hour rhythms in the pineal require an intact sympathetic input from the superior cervical ganglia. The Hartley dataset thus provides evidence that the pineal gland is a highly useful model for studying adrenergically dependent mechanisms regulating variations in ubiquitin ligases, ubiquitin conjugases, and deubiquitinases, mechanisms that may be physiologically relevant not only in the pineal gland, but in all adrenergically innervated tissue.

The pineal gland: A model for adrenergic modulation of ubiquitin ligases

PubMed Central

Liu, Wenjun; Reiter, Russel J.

2017-01-01

Introduction A recent study of the pineal gland of the rat found that the expression of more than 3000 genes showed significant day/night variations (The Hartley dataset). The investigators of this report made available a supplemental table in which they tabulated the expression of many genes that they did not discuss, including those coding for components of the ubiquitin proteasome system. Herein we identify the genes of the ubiquitin proteasome system whose expression were significantly influenced by environmental lighting in the Hartley dataset, those that were stimulated by DBcAMP in pineal glands in culture, and those that were stimulated by norepinephrine. Purpose Using the Ubiquitin and Ubiquitin-like Conjugation Database (UUCA) we identified ubiquitin ligases and conjugases, and deubiquitinases in the Hartley dataset for the purpose of determining whether expression of genes of the ubiquitin proteasome pathway were significantly influenced by day/night variations and if these variations were regulated by autonomic innervation of the pineal gland from the superior cervical ganglia. Methods In the Hartley experiments pineal glands groups of rats sacrificed during the day and groups sacrificed during the night were examined for gene expression. Additional groups of rats had their superior cervical ganglia removed surgically or surgically decentralized and the pineal glands likewise examined for gene expression. Results The genes with at least a 2-fold day/night significant difference in expression included genes for 5 ubiquitin conjugating enzymes, genes for 58 ubiquitin E3 ligases and genes for 6 deubiquitinases. A 35-fold day/night difference was noted in the expression of the gene Sik1, which codes for a protein containing both an ubiquitin binding domain (UBD) and an ubiquitin-associated (UBA) domain. Most of the significant differences in these genes were prevented by surgical removal, or disconnection, of the superior cervical ganglia, and most were responsive, in vitro, to treatment with a cyclic AMP analog, and norepinephrine. All previously described 24-hour rhythms in the pineal require an intact sympathetic input from the superior cervical ganglia. Conclusions The Hartley dataset thus provides evidence that the pineal gland is a highly useful model for studying adrenergically dependent mechanisms regulating variations in ubiquitin ligases, ubiquitin conjugases, and deubiquitinases, mechanisms that may be physiologically relevant not only in the pineal gland, but in all adrenergically innervated tissue. PMID:28212404

Fresh osteochondral allografts in the knee: comparison of primary transplantation versus transplantation after failure of previous subchondral marrow stimulation.

PubMed

Gracitelli, Guilherme C; Meric, Gokhan; Briggs, Dustin T; Pulido, Pamela A; McCauley, Julie C; Belloti, João Carlos; Bugbee, William D

2015-04-01

In most treatment algorithms, osteochondral allograft (OCA) transplantation is regarded as an alternative salvage procedure when other, previous reparative treatments have failed. To compare the outcomes of a retrospective matched-pair cohort of (1) primary OCA transplantation and (2) OCA transplantation after failure of previous subchondral marrow stimulation. Cohort study; Level of evidence, 3. An OCA database was used to identify 46 knees that had OCA transplantation performed as a primary treatment (group 1) and 46 knees that underwent OCA transplantation after failure of previous subchondral marrow stimulation (group 2). All patients had a minimum of 2 years' follow-up. Patients in each group were matched for age (±5 years), diagnosis (osteochondral lesion, degenerative chondral lesion, traumatic chondral injury), and graft size (small, <5 cm2; medium, 5-10 cm2; large, >10 cm2). The groups had similar body mass indexes, sex distributions, and graft locations (femoral condyle, patella, and trochlea. The number and type of further surgeries after the OCA transplantation were assessed; failure was defined as any reoperation resulting in removal of the graft. Functional outcomes were evaluated by use of the modified Merle d'Aubigné-Postel (18-point) scale, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Knee injury and Osteoarthritis Outcomes Score (KOOS), and the Knee Society function (KS-F) scale. Patient satisfaction, according to a 5-point scale from "extremely satisfied" to "dissatisfied," was recorded at the latest follow-up. Eleven of 46 knees (24%) in group 1 had reoperations, compared with 20 of 46 knees (44%) in group 2 (P = .04). The OCA was classified as a failure in 5 knees (11%) in group 1 and 7 knees (15%) in group 2 (P = .53). At 10 years of follow-up, survivorship of the graft was 87.4% and 86% in groups 1 and 2, respectively. Both groups showed improvement in pain and function on all subjective scores from preoperatively to the latest follow-up (all P < .001). Results showed that 87% of patients in group 1 and 97% in group 2 were "satisfied" or "extremely satisfied" with the OCA transplantation. Favorable results were shown in both groups with significant improvement of functional scores and excellent survivorship. Despite the higher reoperation rate in the previously treated group, previous subchondral marrow stimulation did not adversely affect the survivorship and functional outcome of OCA transplantation. © 2015 The Author(s).

Clinical and radiological outcomes with the Durom™ acetabular cup for large-diameter total hip arthroplasty: 177 implants after a mean of 80 months.

PubMed

Saragaglia, D; Belvisi, B; Rubens-Duval, B; Pailhé, R; Rouchy, R C; Mader, R

2015-06-01

Large-diameter metal-on-metal hip prostheses are no longer used, but their outcomes after more than 5 years are unknown. We conducted a retrospective study with a 6.8-year mean follow-up to assess clinical outcomes after Durom™ cup implantation, including the dislocation rate, comparatively to the reference metal-on-polyethylene bearing. We determined the rate of failure ascribable to Durom™ cup use. We also looked for a sharp drop in the implant survival curve during the follow-up period and for factors associated with adverse reactions to metal debris (ARMDs). We hypothesised that clinical outcomes after Durom™ cup implantation were similar to those seen with a metal-on-polyethylene bearing, except for a lower rate of dislocation. We included 177 consecutive THA procedures that were performed between 2005 and 2008 in 165 patients with a mean age of 57.6 ± 9.4 years (range, 31-76 years) and involved the implantation of a Durom™ cup, a femoral head greater than 36mm in diameter, and a PF(®) femoral stem (Zimmer, Etupes, France). The mini-posterior approach was used, with 2mm of acetabular overreaming in 82% of cases, a short femoral neck in 75% of cases, and a mean cup inclination of 34 ± 5° (range, 21-50°). Outcomes were assessed for 156 THA procedures in 146 patients after a mean follow-up of 6 years 8 months. The mean Postel-Merle d'Aubigné score improved from 9.7 ± 2.7 (range, 4-14) to 17.4 ± 1.7 (range, 15-18) and the mean Harris hip score from 45.2 ± 15.3 (range, 9-83) to 96.3 ± 7 (75-100). No episodes of dislocation were recorded. We identified 7 failures ascribable to the Durom™ cup including 6 due to ARMD and 1 to aseptic loosening. Implant survival after a mean of 80months was 95.5% (95% CI, 93.1-99.2), with no sharp drop in the survival curve. The Durom™ cup eliminates the risk of hip dislocation and produces similar functional outcomes to those seen with metal-on-polyethylene bearings after a mean follow-up of 80 months. Nevertheless, given the difficulty in predicting ARMD and hypersensitivity reactions, the Durom™ cup has been discarded and patients carrying it are monitored closely. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Fresh Osteochondral Allograft Transplantation: Is Graft Storage Time Associated With Clinical Outcomes and Graft Survivorship?

PubMed

Schmidt, Kenneth J; Tírico, Luís E; McCauley, Julie C; Bugbee, William D

2017-08-01

Regulatory concerns and the popularity of fresh osteochondral allograft (OCA) transplantation have led to a need for prolonged viable storage of osteochondral grafts. Tissue culture media allow a longer storage time but lead to chondrocyte death within the tissue. The long-term clinical consequence of prolonged storage is unknown. Patients transplanted with OCAs with a shorter storage time would have lower failure rates and better clinical outcomes than those transplanted with OCAs with prolonged storage. Cohort study; Level of evidence, 3. A matched-pair study was performed of 75 patients who received early release grafts (mean storage, 6.3 days [range, 1-14 days]) between 1997 and 2002, matched 1:1 by age, diagnosis, and graft size, with 75 patients who received late release grafts (mean storage time, 20.0 days [range, 16-28 days]) from 2002 to 2008. The mean age was 33.5 years, and the median graft size was 6.3 cm 2 . All patients had a minimum 2-year follow-up. Evaluations included pain, satisfaction, function, failures, and reoperations. Outcome measures included the modified Merle d'Aubigné-Postel (18-point) scale, International Knee Documentation Committee (IKDC) form, and Knee Society function (KS-F) scale. Clinical failure was defined as revision OCA transplantation or conversion to arthroplasty. Among patients with grafts remaining in situ, the mean follow-up was 11.9 years (range, 2.0-16.8 years) and 7.8 years (range, 2.3-11.1 years) for the early and late release groups, respectively. OCA failure occurred in 25.3% (19/75) of patients in the early release group and 12.0% (9/75) of patients in the late release group ( P = .036). The median time to failure was 3.5 years (range, 1.7-13.8 years) and 2.7 years (range, 0.3-11.1 years) for the early and late release groups, respectively. The 5-year survivorship of OCAs was 85% for the early release group and 90% for the late release group ( P = .321). No differences in postoperative pain and function were noted between the groups. Ninety-one percent of the early release group and 93% of the late release group reported satisfaction with OCA results. The transplantation of OCA tissue with prolonged storage is safe and effective for large osteochondral lesions of the knee and has similar clinical outcomes and satisfaction to the transplantation of early release grafts.

[Modified Exeter technique in revision hip surgery].

PubMed

de Thomasson, E; Guingand, O; Terracher, R; Mazel, C

2008-06-01

The Exeter technique opened new perspectives for the treatment of femoral bone stock loss in revision hip arthroplasty. Implant migration in the cement sheath is, however, a frequent finding. According to the promoters of the technique, this would favor transformation of the allograft into living bone. For others it is a worrisome problem since it alters the heterogeneous cement sheath, leading to loosening and final surgical revision, with an incidence up to 20%. We propose an analysis of the mid-term results of the modified Exeter technique with the objective of cementing the distal part of the implant directly into the recipient bone in order to achieve satisfactory primary stability. The purpose of this work was to analyze the consequences of this method on the long-term evolution of the allograft. After preparing the femur, a specific gun is filled with allograph dough obtained from frozen femoral heads fragmented with an acetabular reamer. The Mersilene mesh enables the deposit of a tube of graft material at the desired level. The implant is sealed after impaction of the graft to enable direct distal cementing in contact with the recipient bone. Partial weight bearing is allowed as early as the fifth day and increased progressively to complete weight bearing at three months. Forty-five patients (46 hips) were treated between June 1996 and January 2002. Six patients were not retained for analysis due to insufficient follow-up. For three patients, graft outcome could not be properly assessed due to a major complication. In addition, two patients died and one was lost to follow-up. In all 39 patients (40 hips) were analyzed at mean follow-up of 84 months (range 48-110). There were no cases of revision for femoral loosening. Femoral bone loss was mainly moderate to severe type II and III hips (Sofcot classification) but limited in height (no grade IV in the Endo-Klinik classification). Clinical outcome was excellent in 13 hips, good in 16, fair in nine and poor in two (Postel-Merle-d'Aubigné score). Defective distal cementing with implant migration (less than 5 mm) was noted in four cases followed by secondary stabilization. Transformation of the allograft occurred in 36 cases, associated with corticalization of the recipient bone in 14. This technique is reproducible since primary stability was obtained in 90% of hips, without hindering transformation of the allograft. The results, which are sustained over time, are the same as with the princeps technique and no radiographic evidence of stress shielding could be found.

Evora® chromium-cobalt dual mobility socket: results at a minimum 10 years' follow-up.

PubMed

Leclercq, S; Benoit, J Y; de Rosa, J P; Tallier, E; Leteurtre, C; Girardin, P H

2013-12-01

The Evora chromium-cobalt alloy dual mobility socket claims to display a large articulation tribology different from that of stainless steel models, limiting the risk of intraprosthetic dislocation and wear. The present study reports a minimum of 10years' follow-up in a multicenter prospective series of 200 sockets previously reported on at 5years. The use of chromium-cobalt in dual mobility sockets provides a low rate of failure at 10years, especially as regards to osteolysis and intraprosthetic dislocation. Two hundred hydroxyapatite-coated molded chromium-cobalt sockets without titanium interface were implanted without cement in 194 patients with a mean age of 70 years (range, 32-91 years). Clinical results were assessed on Postel Merle d'Aubigné and Harris scores, plain radiographs and survival analysis. At a mean 11 years' follow-up (10-13 years), 56 patients had died and 31 were lost to follow-up. Four underwent surgical revision (3 femoral components, and 1 socket for migration at 9 years with complete disappearance of the hydroxyapatite). A total of 109 implants were analyzable in 107 patients with a mean age of 81 years (55-93 years). At follow-up, the mean Harris score was 90 (75-96) and the PMA score 16.3 (14-18). There were no cases of loosening (except for the case reoperated on at 9 years) and no acetabular radiolucency or cysts. There were 2 cases of non-evolutive femoral radiolucency and 10 of femoral granuloma, involving head size > 22 mm (P<0.0001) and a cemented titanium stem (P=0.004) as risk factors. There were no dislocations in the large or small articulation. Ten-year survival was 99% (95% CI: 97.3%-100%) with socket revision as censorship criterion. The absence of dislocation in both small and large articulations confirmed the efficacy of the dual mobility concept and suggested an advantage for chromium-cobalt sockets in reducing the rate of intraprosthetic dislocation and preventing blockage of the large articulation by a better performance in the friction couple. Granulomas were associated with wear in cemented titanium stems and with heads greater than 22 mm in diameter. Ten-year survival was 99% (censorship criterion: revision for socket failure); there was, however, one case of socket loosening with disappearance of the hydroxyapatite, indicating that surveillance should be continued in this cohort. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Total hip arthroplasty after a previous pelvic osteotomy: A systematic review and meta-analysis.

PubMed

Shigemura, T; Yamamoto, Y; Murata, Y; Sato, T; Tsuchiya, R; Wada, Y

2018-06-01

There are several reports regarding total hip arthroplasty (THA) after a previous pelvic osteotomy (PO). However, to our knowledge, until now there has been no formal systematic review and meta-analysis published to summarize the clinical results of THA after a previous PO. Therefore, we conducted a systematic review and meta-analysis of results of THA after a previous PO. We focus on these questions as follows: does a previous PO affect the results of subsequent THA, such as clinical outcomes, operative time, operative blood loss, and radiological parameters. Using PubMed, Web of Science, and Cochrane Library, we searched for relevant original papers. The pooling of data was performed using RevMan software (version 5.3, Cochrane Collaboration, Oxford, UK). A p-value<0.05 was judged as significant. Standardized mean differences (SMD) were calculated for continuous data with a 95% confidence interval (CI) was reported. Statistical heterogeneity was assessed based on I 2 using standard χ 2 test. When I 2 >50%, significant heterogeneity was assumed and a random-effects model was applied for the meta-analysis. A fixed-effects model was applied in the absence of significant heterogeneity. Eleven studies were included in this meta-analysis. The pooled results indicated that there was no significant difference in postoperative Merle D'Aubigne-Postel score (I 2 =0%, SMD=-0.15, 95% CI: -0.36 to 0.06, p=0.17), postoperative Harris hip score (I 2 =60%, SMD=-0.23, 95% CI: -0.50 to 0.05, p=0.10), operative time (I 2 =86%, SMD=0.37, 95% CI: -0.09 to 0.82, p=0.11), operative blood loss (I 2 =82%, SMD=0.23, 95% CI: -0.17 to 0.63, p=0.25), and cup abduction angle (I 2 =43%, SMD=-0.08, 95% CI: -0.25 to 0.09, p=0.38) between THA with and without a previous PO. However, cup anteversion angle of THA with a previous PO was significantly smaller than that of without a previous PO (I 2 =77%, SMD=-0.63, 95% CI: -1.13 to -0.13, p=0.01). Systematic review and meta-analysis of results of THA after a previous PO was performed. A previous PO did not affect the results of subsequent THA, except for cup anteversion. Because of the low quality evidence currently available, high-quality randomized controlled trials are required. Level III, meta-analysis of case-control studies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Spatially explicit exposure assessment for small streams in catchments of the orchard growing region `Lake Constance

NASA Astrophysics Data System (ADS)

Golla, B.; Bach, M.; Krumpe, J.

2009-04-01

1. Introduction Small streams differ greatly from the standardised water body used in the context of aquatic risk assessment for the regulation of plant protection products in Germany. The standard water body is static, with a depth of 0.3 m and a width of 1.0 m. No dilution or water replacement takes place. Spray drift happens always in direction to the water body. There is no variability in drift deposition rate (90th percentile spray drift deposition values [2]). There is no spray drift filtering by vegetation. The application takes place directly adjacent to the water body. In order to establish a more realistic risk assessment procedure the Federal Office for Consumer Protection and Food Safety (BVL) and the Federal Environment Agency (UBA) aggreed to replace deterministic assumptions with data distributions and spatially explicit data and introduce probabilistic methods [3, 4, 5]. To consider the spatial and temporal variability in the exposure situations of small streams the hydraulic and morphological characteristics of catchments need to be described as well as the spatial distribution of fields treated with pesticides. As small streams are the dominant type of water body in most German orchard regions, we use the growing region Lake Constance as pilot region. 2. Materials and methods During field surveys we derive basic morphological parameters for small streams in the Lake Constance region. The mean water width/depth ratio is 13 with a mean depth of 0.12 m. The average residence time is 5.6 s/m (n=87) [1]. Orchards are mostly located in the upper parts of the catchments. Based on an authoritative dataset on rivers and streams of Germany (ATKIS DLM25) we constructed a directed network topology for the Lake Constance region. The gradient of the riverbed is calculated for river stretches of > 500 m length. The network for the pilot region consists of 2000 km rivers and streams. 500 km stream length are located within a distance of 150 m to orchards. Within this distance a spray drift exposure with adverse effects is theoretically possible [6]. The network is segmented to approx. 80'000 segments of 25 m length. One segment is the basic element of the exposure assessment. Based on the Manning-Strickler formula and empirically determined relations two equations are developed to express the width and depth of the streams and the flow velocity [7]. Using Java programming and spatial network analysis within Oracle 10g/Spatial DBMS we developed a tool to simulate concentration over time for all single 25 m segments of the stream network. The analysis considers the spatially explicit upstream exposure situations due to the locations of orchards and recovery areas in the catchments. The application which takes place on a specific orchard is simulated according to realistic application patterns or to the simplistic assumption that all orchards are sprayed on the same day. 3. Results The results of the analysis are distributions of time average concentrations (mPEC) for all single stream segments of the stream network. The averaging time window can be defined flexibly between 1 h (mPEC1h) to 24 h (mPEC24h). Spatial network analysis based on georeferenced hydraulic and morphological parameters proved to be a suitable approach for analysing the exposure situation of streams under more realistic aspects. The time varying concentration of single stream segments can be analysed over a vegetation period or a single day. Stream segments which exceed a trigger concentration or segments with a specific pulse concentration pattern in given time windows can be identified and be addressed by e.g. implementing additional drift mitigation measures. References [1] Golla, B., J. Krumpe, J. Strassemeyer, and V. Gutsche. (2008): Refined exposure assessment of small streams in German orchard regions. Part 1. Results of a hydromorphological survey. Journal für Kulturpflanzen (submitted). [2] Rautmann, D., Streloke, M, and Winkler, R (1999): New basic drift values in the authorization procedure for plant protection products, pp. 133-141. In Workshop on risk management and risk mitigation measures in the context of authorization of plant protection products [3] Klein, A. W., Dechet, F., and Streloke, M (2003): Probabilistic Assessment Method for Risk Analysis in the framework of Plant Protection Product Authorisation, Industrieverband Agrar (IVA, 2006), Frankfurt/Main [4] Schulz R, Stehle S, Elsaesser F, Matezki S, Müller A, Neumann M, Ohliger R, Wogram J, Zenker K. 2008. Geodata-based Probabilistic Risk Assessment and Management of Pesticides in Germany, a Conceptual Framework. IEAM_2008-032R [5] Kubiak, R., Hommen, Bach, M., Classen, G. Fent, H.-G. Frede, A. Gergs, B. Golla, M. Klein, J. Krumpe, S. Matetzki, A. Müller, M. Neumann,T. G. Preuss, H. T. Ratte, M. Roß-Nickoll, S. Reichenberger, C. Schäfers, T. Strauss, A. Toschki, M. Trapp, J. Wogram (2009): A new GIS based approach for the assessment and management of environmental risks of plant protection, SETAC EUROPE Göteborg [6] Enzian, S. ,Golla., B. (2006) A method for the identification and classification of "save distance" cropland to the potential drift exposure of pesticides towards surface waters. UBA-Texte [7] Bach, M., Träbing, K. and Frede, H.-G. (2004): Morphological Characteristics of small rivers in the context of probabilistic exposure assessment. Nachrichtenblatt des Deutschen Pflanzenschutzdienstes 56

Ubiquitin ligase SYVN1/HRD1 facilitates degradation of the SERPINA1 Z variant/α-1-antitrypsin Z variant via SQSTM1/p62-dependent selective autophagy.

PubMed

Feng, Lijie; Zhang, Jin; Zhu, Na; Ding, Qian; Zhang, Xiaojie; Yu, Jishuang; Qiang, Weimin; Zhang, Zhetao; Ma, Yuyang; Huang, Dake; Shen, Yujun; Fang, Shengyun; Yu, Yifan; Wang, Haiping; Shen, Yuxian

2017-04-03

SERPINA1/AAT/α-1-antitrypsin (serpin family A member 1) deficiency (SERPINA1/ AAT-D) is an autosomal recessive disorder characterized by the retention of misfolded SERPINA1/AAT in the endoplasmic reticulum (ER) of hepatocytes and a significant reduction of serum SERPINA1/AAT level. The Z variant of SERPINA1/AAT, containing a Glu342Lys (E342K) mutation (SERPINA1 E342K /ATZ), the most common form of SERPINA1/AAT-D, is prone to misfolding and polymerization, which retains it in the ER of hepatocytes and leads to liver injury. Both proteasome and macroautophagy/autophagy pathways are responsible for disposal of SERPINA1 E342K /ATZ after it accumulates in the ER. However, the mechanisms by which SERPINA1 E342K /ATZ is selectively degraded by autophagy remain unknown. Here, we showed that ER membrane-spanning ubiquitin ligase (E3) SYVN1/HRD1 enhances the degradation of SERPINA1 E342K /ATZ through the autophagy-lysosome pathway. We found that SYVN1 promoted SERPINA1 E342K /ATZ, especially Triton X 100-insoluble SERPINA1 E342K /ATZ clearance. However, the effect of SYVN1 in SERPINA1 E342K /ATZ clearance was impaired after autophagy inhibition, as well as in autophagy-related 5 (atg5) knockout cells. On the contrary, autophagy induction enhanced SYVN1-mediated SERPINA1 E342K /ATZ degradation. Further study showed that SYVN1 mediated SERPINA1 E342K /ATZ ubiquitination, which is required for autophagic degradation of SERPINA1 E342K /ATZ by promoting the interaction between SERPINA1 E342K /ATZ and SQSTM1/p62 for formation of the autophagy complex. Interestingly, SYVN1-mediated lysine 48 (K48)-linked polyubiquitin chains that conjugated onto SERPINA1 E342K /ATZ might predominantly bind to the ubiquitin-associated (UBA) domain of SQSTM1 and couple the ubiquitinated SERPINA1 E342K /ATZ to the lysosome for degradation. In addition, autophagy inhibition attenuated the suppressive effect of SYVN1 on SERPINA1 E342K /ATZ cytotoxicity, and the autophagy inducer rapamycin enhanced the suppressive effect of SYVN1 on SERPINA1 E342K /ATZ-induced cell apoptosis. Therefore, this study proved that SYVN1 enhances SERPINA1 E342K /ATZ degradation through SQSTM1-dependent autophagy and attenuates SERPINA1 E342K /ATZ cytotoxicity.

Global Analysis of miRNA-mRNA Interaction Network in Breast Cancer with Brain Metastasis.

PubMed

Li, Zhixin; Peng, Zhiqiang; Gu, Siyu; Zheng, Junfang; Feng, Duiping; Qin, Qiong; He, Junqi

2017-08-01

MicroRNAs (miRNAs) have been linked to a number of cancer types including breast cancer. The rate of brain metastases is 10-30% in patients with advanced breast cancer which is associated with poor prognosis. The potential application of miRNAs in the diagnostics and therapeutics of breast cancer with brain metastasis is an area of intense interest. In an initial effort to systematically address the differential expression of miRNAs and mRNAs in primary breast cancer which may provide clues for early detection of brain metastasis, we analyzed the consequent changes in global patterns of gene expression in Gene Expression Omnibus (GEO) data set obtained by microarray from patients with in situ carcinoma and patients with brain metastasis. The miRNA-pathway regulatory network and miRNA-mRNA regulatory network were investigated in breast cancer specimens from patients with brain metastasis to screen for significantly dysregulated miRNAs followed by prediction of their target genes and pathways by Gene Ontology (GO) analysis. Functional coordination of the changes of gene expression can be modulated by individual miRNAs. Two miRNAs, hsa-miR-17-5p and hsa-miR-16-5p, were identified as having the highest associations with targeted mRNAs [such as B-cell lymphoma 2 (BCL2), small body size/mothers against decapentaplegic 3 (SMAD3) and suppressor of cytokine signaling 1 (SOCS1)] and pathways associated with epithelial-mesenchymal transitions and other processes linked with cancer metastasis (including cell cycle, adherence junctions and extracellular matrix-receptor interaction). mRNAs for two genes [HECT, UBA and WWE domain containing 1 (HUWE1) and BCL2] were found to have the highest associations with miRNAs, which were down-regulated in brain metastasis specimens of breast cancer. The change of 11 selected miRNAs was verified in The Cancer Genome Atlas (TCGA) breast cancer dataset. Up-regulation of hsa-miR-17-5p was detected in triple-negative breast cancer tissues in TCGA. Furthermore, a negative correlation of hsa-miR-17-5p with overall survival and phosphatase and tensin homolog (PTEN) and BCL2 target genes was found in TCGA breast cancer specimens. Our findings provide a functionally coordinated expression pattern of different families of miRNAs that may have potential to provide clinicians with a strategy to treat breast cancer with brain metastasis from a systems-rather than a single-gene perspective. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Implementing SDG 15.3 on Land Degradation Neutrality in the EU and EU Member States

NASA Astrophysics Data System (ADS)

Wunder, Stephanie; Starke, Sue Martina; Frelih-Larsen, Ana; Kaphengst, Timo

2017-04-01

The continuing degradation of land and soils is a severe threat to the provision of ecosystem services and economic development. Sustainable use of land and soils are therefore an integral part of the "Agenda 2030" with its 17 Sustainable Development Goals (SDGs) and 169 targets adopted by the UNGeneral Assembly in September 2015. The SDGs provide new opportunities for an ambitious and integrated environmental policy worldwide and in the EU. Among the many relevant targets that directly or indirectly address soils (such as goals on zero hunger, well being, clean energy, climate change, water and sustainable cities), target 15.3 that aims to achieve "a land degradation-neutral world" by 2030 is the most relevant. The concept of "Land Degradation Neutrality" (LDN) is not only about halting the loss of healthy and fertile land, but also actively reversing degradation by restoring land in order to counterbal-ance losses that cannot be avoided. It is a very ambitious target but due to a lack of balancing mechanisms for degradation and restoration in most countries also a new concept. Land Degra-dation Neutrality therefore both needs a scientific conceptual framework as well as a political debate about its implementation and development of instruments. In the EU and its Member States, this debate can also serve as a catalyst to revive the discussion on a common soil policy in Europe after the withdrawal of the proposal for a soil framework directive in 2014. To analyze options for the implementation of target 15.3 in Germany and Europe the research project "Implementing the Sustainable Development Goals on Soils in Germany" (http://ecologic.eu/12876) is currently carried out by the Ecologic Institute on behalf of the Ger-man Environment Agency (UBA) and the German Federal Environment Ministry (BMUB). The project will run until spring 2017 and the session "European Environmental Policies and Sustainability" at the EGU will be an ideal opportunity to present the final outcomes of the project and give participants an overview of this very dynamic political process and its science policy interface. Specifically, the presentation can provide an overview about two key results of the project: A) Steps and guiding questions to implement LDN on a national level for policy makers (including a reflection about key definitions and concept) B) Appropriate indicators for LDN (with a special focus on Land Use Change) The results are based on a literature review, more than 50 international expert interviews and discussions within two German workshops and one international workshop (that brought together 15 EU Member State representatives, EEA, UNCCD and the European Commission) to discuss the political options to implement LDN. The results also build on the extensive work that the UNCCD and the global Target Setting Programme have conducted to further develop and define the concept of land degradation neutrality. The continuing degradation of land and soils is a severe threat to the provision of ecosystem services and economic development. Sustainable use of land and soils are therefore an integral part of the "Agenda 2030" with its 17 Sustainable Development Goals (SDGs) and 169 targets adopted by the UNGeneral Assembly in September 2015. The SDGs provide new opportunities for an ambitious and integrated environmental policy worldwide and in the EU. Among the many relevant targets that directly or indirectly address soils (such as goals on zero hunger, well being, clean energy, climate change, water and sustainable cities), target 15.3 that aims to achieve "a land degradation-neutral world" by 2030 is the most relevant. The concept of "Land Degradation Neutrality" (LDN) is not only about halting the loss of healthy and fertile land, but also actively reversing degradation by restoring land in order to counterbal-ance losses that cannot be avoided. It is a very ambitious target but due to a lack of balancing mechanisms for degradation and restoration in most countries also a new concept. Land Degra-dation Neutrality therefore both needs a scientific conceptual framework as well as a political debate about its implementation and development of instruments. In the EU and its Member States, this debate can also serve as a catalyst to revive the discussion on a common soil policy in Europe after the withdrawal of the proposal for a soil framework directive in 2014. To analyze options for the implementation of target 15.3 in Germany and Europe the research project "Implementing the Sustainable Development Goals on Soils in Germany" (http://ecologic.eu/12876) is currently carried out by the Ecologic Institute on behalf of the Ger-man Environment Agency (UBA) and the German Federal Environment Ministry (BMUB). The project runs until spring 2017 and the session "European Environmental Policies and Sustainability" at the EGU is an ideal opportunity to present the final outcomes of the project and give participants an overview of this very dynamic political process and its science policy interface. Specifically, the presentation can provide an overview about two key results of the project: A) Steps and guiding questions to implement LDN on a national level for policy makers (including a reflection about key definitions and concept) B) Appropriate indicators for LDN (with a special focus on Land Use Change) The results are based on a literature review, more than 50 international expert interviews and discussions within two German workshops and one international workshop (that brought together 15 EU Member State representatives, EEA, UNCCD and the European Commission) to discuss the political options to implement LDN. The results also build on the extensive work that the UNCCD and the global Target Setting Programme have conducted to further develop and define the concept of land degradation neutrality.

Reconstruction of the pelvic brim and its role in the reduction accuracy of displaced T-shaped acetabular fracture.

PubMed

Harnroongroj, T; Asavamongkolkul, A; Chareancholvanich, K

2000-05-01

Open reduction of the displaced T-shaped acetabular fracture has a problem of accuracy of the fracture reduction. This study was carried out to demonstrate that the reconstruction of the pelvic brim by approaching the pubo-acetabular fragment plays a role in the accuracy of the reduction of displaced T-shaped acetabular fractures. From 1975 to 1990, a retrospective study was carried out of 22 patients who sustained a displaced T-shaped acetabular fracture. The patients were operated on by open reduction and internal fixation of the ischio-acetabular fragment to the posterior column without restoration of the pelvic brim. Radiographs of the pelvis were reviewed. The result showed that there was displacement of the pubo-acetabular fragment including the medial wall in all cases. As the result of this study, a prospective study between 1990 and 1997 was carried out of 15 patients who sustained displaced T-shaped acetabular fractures including 3 cases with medial displacement of the femoral head. The pubo-acetabular fragment was anatomically reduced and fixed to the anterior column of the acetabulumn as the first approach to restore a disrupted pelvic brim. There, patterns of the acetabular fracture were subsequently re-evaluated especially the ischio-acetabular fragment including the position of the femoral head by using an intraoperative portable X-ray technique. The stability of the hip joint was assessed by hip flexion. The intraoperative radiograph appearances of the ischio-acetabular fragment were visually confirmed by a second surgical exposure. The results showed that the intraoperative radiographs gave spontaneous reduction of the ischio-acetabular fragment in all patients except one. There was a reduction of the displaced femoral head into the hip socket in the three patients. The hip joints were stable in all patients. The second surgical exposure showed that there was good spontaneous reduction of the ischio-acetabular fragment to the posterior column by ligamentotaxis in 14 patients. Therefore, it is not necessary to address the ischio-acetabular fragment. In the exceptional case, the ischio-acetabular fragment was displaced as a free bone which could not be reduced by ligamentotaxis. However, reduction and internal fixation of the ischio-acetabular fragment to the posterior column for complete re-application of the hip joint onto the pelvic ring of this case was facilitated. Postoperative 2 year and 5 year follow-up showed that the fracture had healed without heterotrophic ossification or premature osteoarthrosis of the hip joint. The exceptional case had a broken plate at the anterior column of the acetabulum. Hip function was evaluated clinically using Merle D' Aubigne's hip score. All patients had a "very good score". The study showed that reconstruction of the pelvic brim by anatomical reduction and fixation of the pubo-acetabular fragment to the anterior column plays an important role in the accuracy of fracture reduction of a displaced T-shaped acetabular fracture.

Slum upgrading strategies involving physical environment and infrastructure interventions and their effects on health and socio-economic outcomes.

PubMed

Turley, Ruth; Saith, Ruhi; Bhan, Nandita; Rehfuess, Eva; Carter, Ben

2013-01-31

Slums are densely populated, neglected parts of cities where housing and living conditions are exceptionally poor. In situ slum upgrading, at its basic level, involves improving the physical environment of the existing area, such as improving and installing basic infrastructure like water, sanitation, solid waste collection, electricity, storm water drainage, access roads and footpaths, and street lighting, as well as home improvements and securing land tenure. To explore the effects of slum upgrading strategies involving physical environment and infrastructure interventions on the health, quality of life and socio-economic wellbeing of urban slum dwellers in low and middle income countries (LMIC). Where reported, data were collected on the perspectives of slum dwellers regarding their needs, preferences for and satisfaction with interventions received. We searched for published and unpublished studies in 28 bibliographic databases including multidisciplinary (for example Scopus) and specialist databases covering health, social science, urban planning, environment and LMIC topics. Snowballing techniques included searching websites, journal handsearching, contacting authors and reference list checking. Searches were not restricted by language or publication date. We included studies examining the impact of slum upgrading strategies involving physical environment or infrastructure improvements (with or without additional co-interventions) on the health, quality of life and socio-economic wellbeing of LMIC urban slum dwellers. Randomised controlled trials (RCTs), controlled before and after studies (CBAs) and interrupted time series (ITS) were eligible for the main analysis. Controlled studies with only post-intervention data (CPI) and uncontrolled before and after (UBA) studies were included in a separate narrative to examine consistency of results and to supplement evidence gaps in the main analysis. Two authors independently extracted data and assessed risk of bias for each study. Differences between the included study interventions and outcomes precluded meta-analysis so the results were presented in a narrative summary with illustrative harvest plots. The body of evidence for outcomes within the main analysis was assessed according to GRADE as very low, low, moderate or high quality. We identified 10,488 unique records, with 323 screened as full text. Five studies were included for the main analysis: one RCT with a low risk, two CBAs with a moderate risk and two CBAs with a high risk of bias. Three CBAs evaluated multicomponent slum upgrading strategies. Road paving only was evaluated in one RCT and water supply in one CBA. A total of 3453 households or observations were included within the four studies reporting sample sizes.Most health outcomes in the main studies related to communicable diseases, for which the body of evidence was judged to be low quality. One CBA with a moderate risk of bias found that diarrhoeal incidence was reduced in households which received water connections from a private water company (risk ratio (RR) 0.53; 95% confidence interval (CI) 0.27 to 1.04) and the severity of diarrhoeal episodes (RR 0.48; 95% CI 0.19 to 1.22). There was no effect for duration of diarrhoea. Road paving did not result in changes in parasitic infections or sickness in one RCT. After multicomponent slum upgrading, claims for a waterborne disease as opposed to a non-waterborne disease reduced (RR 0.64; 95% CI 0.27 to 0.98) in one CBA with a high risk of bias but there was no change in sanitation-related mortality in a CBA with a moderate risk of bias.The majority of socio-economic outcomes reported within the main studies related to financial poverty, for which the body of evidence was of very low quality. Results were mixed amongst the main studies; one RCT and two CBAs reported no effect on the income of slum dwellers following slum upgrading. One further CBA found significant reduction in monthly water expenditure (mean difference (MD) -17.11 pesos; 95% CI -32.6 to -1.62). One RCT also showed mixed results for employment variables, finding no effect on unemployment levels but increased weekly worked hours (MD 4.68; 95% CI -0.46 to 9.82) and lower risk of residents intending to migrate for work (RR 0.78; 95% CI 0.60 to 1.01).There was no evidence available to assess the impact of slum upgrading on non-communicable diseases or social capital. Maternal and perinatal conditions, infant mortality, nutritional deficiencies, injuries, self-reported quality of life, education and crime were evaluated in one study each.Nine supporting studies were included that measured varying outcomes (6794 households or observations within eight studies reporting sample sizes). One CPI evaluated cement flooring only while three UBAs and five CPIs evaluated multicomponent slum upgrading strategies. All studies but one had a high risk of bias.The studies reinforced main study findings for diarrhoea incidence and water-related expenditure. Findings for parasitic infections and financial poverty were inconsistent with the main studies. In addition, supporting studies reported a number of disparate outcomes that were not evaluated in the main studies.Five supporting studies included some limited information on slum dweller perspectives. They indicated the importance of appropriate siting of facilities, preference for private facilities, delivering synergistic interventions together, and ensuring that infrastructure was fit for purpose and systems were provided for cleaning, maintenance and repair. A high risk of bias within the included studies, heterogeneity and evidence gaps prevent firm conclusions on the effect of slum upgrading strategies on health and socio-economic wellbeing. The most common health and socio-economic outcomes reported were communicable diseases and indicators of financial poverty. There was a limited but consistent body of evidence to suggest that slum upgrading may reduce the incidence of diarrhoeal diseases and water-related expenditure. The information available on slum dwellers' perspectives provided some insight to barriers and facilitators for successful implementation and maintenance of interventions.The availability and use of reliable, comparable outcome measures to determine the effect of slum upgrading on health, quality of life and socio-economic wellbeing would make a useful contribution to new research in this important area. Given the complexity in delivering slum upgrading, evaluations should look to incorporate process and qualitative information alongside quantitative effectiveness data to determine which particular interventions work (or don't work) and for whom.

Smoking behavior and use of tobacco industry sponsored websites among medical students and young physicians in Argentina.

PubMed

Salgado, M Victoria; Mejia, Raul; Kaplan, Celia P; Perez-Stable, Eliseo J

2014-02-06

Internet-based marketing has become an attractive option for promoting tobacco products due to its potential to avoid advertising restrictions. In Argentina, several cigarette brands have designed websites for the local market, which promote user participation. The intent of the study was to report on the use of tobacco company-sponsored websites by medical students and recently graduated physicians. An online self-administered survey was conducted among eligible medical students and recent graduates from the University of Buenos Aires (UBA). Sampling was from lists of email addresses of students enrolled in two required courses. Eligibility criteria were ages 18-30 years and reporting on smoking status. Questions on Internet use included accessing a tobacco brand website at least once during their lifetime and any use of tobacco promotional materials. The response rate was 35.08% (1743/4969). The final sample included 1659 participants: 73.06% (1212/1659) were women and mean age was 26.6 years (SD 1.9). The majority were current medical students (55.70%, 924/1659) and 27.31% (453/1659) were current smokers. Men were more likely to report having seen a tobacco advertisement on the Internet (P=.001), to have received a tobacco promotion personally addressed to them (P=.03), to have used that promotion (P=.02), and to have accessed a tobacco-sponsored website (P=.01). Among respondents, 19.35% (321/1659) reported having accessed a tobacco-sponsored website at least once in their lifetime and almost all of them (93.8%, 301/321) accessed these sites only when it was necessary for participating in a marketing promotion. Most people logging on for promotions reported entering once a month or less (58.9%, 189/321), while 25.5% (82/321) reported accessing the tobacco industry Internet sites once a week or more. In adjusted logistic regression models, participants were more likely to have accessed a tobacco brand website if they were former smokers (OR 2.45, 95% CI 1.42-4.22) or current (OR 8.12, 95% CI 4.66-14.16), if they reported having seen a tobacco advertisement on the Internet (OR 2.44, 95% CI 1.77-3.37), received a tobacco promotion personally addressed to them (OR 5.62; 95% CI 4.19-7.55), or used one of these promotions (OR 14.05, 95% CI 9.21-21.43). Respondents were more likely to be current smokers if they received a tobacco promotion (OR 2.64, 95% CI 2.02-3.45) or if they used one of these promotions (OR 1.93, 95% CI 1.31-2.85). Our study suggests that tobacco industry websites reach medical students and young physicians in a middle-income country with their marketing promotions. Current or proposed legislation to ban tobacco advertising needs to include Internet sites and related social media.

Smoking Behavior and Use of Tobacco Industry Sponsored Websites Among Medical Students and Young Physicians in Argentina

PubMed Central

Salgado, M Victoria; Mejia, Raul; Kaplan, Celia P

2014-01-01

Background Internet-based marketing has become an attractive option for promoting tobacco products due to its potential to avoid advertising restrictions. In Argentina, several cigarette brands have designed websites for the local market, which promote user participation. Objective The intent of the study was to report on the use of tobacco company-sponsored websites by medical students and recently graduated physicians. Methods An online self-administered survey was conducted among eligible medical students and recent graduates from the University of Buenos Aires (UBA). Sampling was from lists of email addresses of students enrolled in two required courses. Eligibility criteria were ages 18-30 years and reporting on smoking status. Questions on Internet use included accessing a tobacco brand website at least once during their lifetime and any use of tobacco promotional materials. Results The response rate was 35.08% (1743/4969). The final sample included 1659 participants: 73.06% (1212/1659) were women and mean age was 26.6 years (SD 1.9). The majority were current medical students (55.70%, 924/1659) and 27.31% (453/1659) were current smokers. Men were more likely to report having seen a tobacco advertisement on the Internet (P=.001), to have received a tobacco promotion personally addressed to them (P=.03), to have used that promotion (P=.02), and to have accessed a tobacco-sponsored website (P=.01). Among respondents, 19.35% (321/1659) reported having accessed a tobacco-sponsored website at least once in their lifetime and almost all of them (93.8%, 301/321) accessed these sites only when it was necessary for participating in a marketing promotion. Most people logging on for promotions reported entering once a month or less (58.9%, 189/321), while 25.5% (82/321) reported accessing the tobacco industry Internet sites once a week or more. In adjusted logistic regression models, participants were more likely to have accessed a tobacco brand website if they were former smokers (OR 2.45, 95% CI 1.42-4.22) or current (OR 8.12, 95% CI 4.66-14.16), if they reported having seen a tobacco advertisement on the Internet (OR 2.44, 95% CI 1.77-3.37), received a tobacco promotion personally addressed to them (OR 5.62; 95% CI 4.19-7.55), or used one of these promotions (OR 14.05, 95% CI 9.21-21.43). Respondents were more likely to be current smokers if they received a tobacco promotion (OR 2.64, 95% CI 2.02-3.45) or if they used one of these promotions (OR 1.93, 95% CI 1.31-2.85). Conclusions Our study suggests that tobacco industry websites reach medical students and young physicians in a middle-income country with their marketing promotions. Current or proposed legislation to ban tobacco advertising needs to include Internet sites and related social media. PMID:24509433

A model approach to project the start of egg laying of Great Tit (Parus major L.) in response to climate change.

PubMed

Chmielewski, Frank-M; Blümel, Klaus; Scherbaum-Heberer, Carina; Koppmann-Rumpf, Bettina; Schmidt, Karl-Heinz

2013-03-01

The aim of this study was to select a phenological model that is able to calculate the beginning of egg laying of Great Tit (Parus major) for both current and future climate conditions. Four models (M1-M4) were optimised on long-term phenological observations from the Ecological Research Centre Schlüchtern (Hessen/Germany). Model M1 was a common thermal time model that accumulates growing degree days (GDD) on an optimised starting date t (1). Since egg laying of Great Tit is influenced not only by air temperature but also by photoperiod, model M1 was extended by a daylength term to give M2. The other two models, M3 and M4, correspond to M1 and M2, but t (1) was intentionally set to 1 January, in order to consider already rising temperatures at the beginning of the year. A comparison of the four models led to following results: model M1 had a relatively high root mean square error at verification (RMSE(ver)) of more than 4 days and can be used only to calculate the start of egg laying for current climate conditions because of the relatively late starting date for GDD calculation. The model failed completely if the starting date was set to 1 January (M3). Consideration of a daylength term in models M2 and M4 improved the performance of both models strongly (RMSE(ver) of only 3 days or less), increased the credibility of parameter estimation, and was a precondition to calculate reliable projections in the timing of egg laying in birds for the future. These results confirm that the start of egg laying of Great Tit is influenced not only by air temperature, but also by photoperiod. Although models M2 and M4 both provide comparably good results for current climate conditions, we recommend model M4-with a starting date of temperature accumulation on 1 January-for calculating possible future shifts in the commencement of egg laying. Our regional projections in the start of egg laying, based on five regional climate models (RCMs: REMO-UBA, ECHAM5-CLM, HadCM3-CLM, WETTREG-0, WETTREG-1, GHG emission scenario A1B), indicate that in the near future (2011-2040) no significant change will take place. However, in the mid- (2041-2070) and long-term (2071-2100) range the beginning of egg laying could be advanced significantly by up to 11 days on average of all five RCMs. This result corresponds to the already observed shift in the timing of egg laying by about 1 week, due mainly to an abrupt increase in air temperature at the end of the 1980s by 1.2 K between April and May. The use of five regional climate scenarios additionally allowed to estimate uncertainties among the RCMs.

Long-term survivorship of the Corail™ standard stem.

PubMed

Louboutin, L; Viste, A; Desmarchelier, R; Fessy, M-H

2017-11-01

The Corail™ stem, which was first introduced in 1986, has since been modified twice: first to make the neck thinner and then to change the location of the laser markings. The survival and complications of the first-generation straight, titanium, hydroxyapatite-coated stem are known; however, there is little specific information about the latest-generation stem. This led us to conduct a retrospective study to determine the: (1) long-term survival; (2) clinical and radiographic outcomes; (3) complications; and (4) risk factors for revision of the newest Corail™ stem. The newest Corail™ AMT (Articul/EZE™ Mini Taper) standard stem has comparable survival to prior models. This single-center, retrospective study included 133 patients (140 hips), who underwent primary total hip arthroplasty (THA), between January and December 2004, in which a Corail™ Standard stem was implanted using a posterolateral approach. Patients who underwent revision THA, THA due to femoral neck fracture or who received lateralized (offset) stems were excluded. The mean age at the time of THA was 69±13 years [35-92] in 85 men (61%) and 55 women (39%) who had a mean BMI of 27kg/m 2 ±11 [16-39]. At the latest follow-up, 32 patients (32 hips) had died and 8 patients (8 hips) had less than 3 years' follow-up, thus were not included in the clinical evaluation. The Merle d'Aubigné (PMA) score was collected. The stem's survivorship was calculated using the Kaplan-Meier method with revision for aseptic loosening and revision or implant removal for any reason as the end-points. The Cox model was used to analyze risk factors for revision. The mean follow-up was 10±3 years [3-12]. The PMA score was 12±2.6 [5-17] preoperatively and 16±2.7 [7-18] at the last follow-up (P<0.00001). Eighteen complications (12.8%) were recorded at the last follow-up. There were 15 early complications: 6 dislocations, 5 calcar fractures (4 treated by wire cerclage and 1 by stem change plus wire cerclage), 2 greater trochanter fractures (treated non-surgically) and 2 cases of sciatic nerve palsy. There were 3 late complications: 2 cases of iliopsoas irritation and 1 ceramic insert fracture. Stem survival for surgical revision due to aseptic loosening was 98% (95% CI: [0.96-1]). At 12 years, 95% of stems had not been revised or removed (95% CI: [0.92-0.99]). Being less than 58 years of age at the time of surgery was the only risk factor significantly associated with stem revision for any reason (P=0.04). Survival of the Corail™ Standard stem is similar to that of previous generation stems. The changes made in this stem solved the neck failure problem and did not induce new complications. Level IV (retrospective study). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Femoral osteotomy for severe hip osteoarthritis: an actuarial analysis of results].

PubMed

Dujardin, F; Matsoukis, J; Duparc, F; Biga, N; Thomine, J M

1994-01-01

In cases of severe hip osteoarthritis in young patients, the intertrochanteric osteotomy can delay total hip arthroplasty. The main advantage of the osteotomy is to preserve the bone stock. The main disadvantages are the lasting postoperative invalidity and the varying longterm success rate. Our aim was to quantify these disadvantages using survivorship analysis. The study included 64 patients (65 osteotomies) ranging from 16 to 68 years. The osteotomies were performed between 1975 and 1987. The osteoarthritis was stage III or IV, with a joint space less than 50 per cent. Osteoarthritis was primitive in 25 cases and secondary in the others. The osteotomy always included a medial displacement of the shaft according to the principle of Mac Murray's procedure, but also 22 cases (33.8 per cent) had a varus angulation and 19 (29.2 per cent) a valgus angulation. The preoperative pain score according to the Merle d'Aubigné (MDA) grading was 2.6 (1 to 4) and the global functional score was 11.1 (5 to 15). The patients were reviewed in 1991 and examined clinically and radiographically. The results of the 65 cases were distributed into 3 groups: -29 cases having reached the follow-up without difficulty, -7 patients were lost for follow-up examination, 6 of these latter than 9 years, -29 patients taking osteotomy failure as a pain lesser than the 3 MDA score. The postoperative delay to obtain the best functional result was 6 to 24 months (mean: 13.65). This result ranged from 5 to 17 MDA score (mean: 15) with pain ranging from 2 to 6 (mean: 5). The survivorship analysis curve showed 67.5 +/- 19.5 per cent survival for all osteotomies to the interval of 9-10 years. There were 3 types of results: -3 early failures (4.6 per cent) one because of a deep infection, -in 7 cases, after a short initial functional improvement, there was a progressive degradation leading to failure in 3.7 years (2 to 6 years), -55 cases with a lasting period of functional improvement, 26 osteotomies leading to failure in 3.5 to 15 postoperative years and, 29 cases having reached the follow-up (7 to 16 years mean 10 years). There was radiographic improvement of the osteoarthritis increasing the joint space in 59 cases (90.7 per cent). There was no radiographic improvement in the 6 other cases, including the 2 functional failures. The functional degradation appeared parallel to the radiographic degradation leading to a decrease of joint space to 90 per cent. We tested differences between various groups using Log Rank test. We found no difference in survival between the 3 different types of osteotomy. The results of this study can help to choose between intertrochanteric osteotomy and THA in the case of severe osteoarthritis. The best functional result of the osteotomy is in one postoperative year, with a mean MDA score of 15 and a mean pain score of 5. It appears that we do not predict the duration of functional improvement, the patient has 2/3 chances that this improvement reaches 10 years.

A review on the patterns of river material fluxes, coastal plume dispersal, shelf sediment facies, and anthropogenic impacts of the Tropical Land-Sea Interface, Sergipe/Alagoas, Northeast Brazil

NASA Astrophysics Data System (ADS)

Knoppers, B.; Medeiros, P. R. P.; de Souza, W. F. L.; Oliveira, E. N.; Fontes, L. C. da S.; do Carmo, M. S.; Carvalho, I. S.; Silva, M. C.; Brandini, N.; Carneiro, M. E.

2012-04-01

This study couples published and unpublished information on the alterations of continental material fluxes, plume dispersal patterns and coastal erosion induced by natural and human impacts to the distribution of sediment facies and sedimentation rates of the continental shelf of the States of Sergipe and Alagoas, northeastern Brazil (Lats. 8o56,2' and 11o20,0' S, Longs. 35o07,7' and 37o14,2' W). Historical data on river flow and material fluxes of 7 rivers, including the São Francisco river (L = 2850 km, AB = 634000 km2), were obtained from own measurements and from the national data bank of ANA (National Agency of Waters, www.ana.gov.br) with the softwares HIDRO 1.2 and SisCAH 1.0. Historical data on the distribution of sediments and their elemental composition of the shelf from the AKAROA (1965) campaign with 190 sampling stations (scale 1:1.000.000; Kempf, 1972, Summerhayes et al. 1975 & 1976, Coutinho, 1976) were revisited and new digital maps constructed with ArcGIS 9.3. Comparisons are made from new maps from recent campaigns (scale 1:250.000) performed by the consortium GEORIOEMAR/ UFS/ CENPES/ PETROBRÁS (2010). Statistical analyses with all parameters revealed that the shelf harbors 4 major regional sedimentary domains (i.e. A to D), reflecting the interaction between continental inputs and the impact of the oligotrophic South Equatorial Current (SEC) upon the shelf. The domains are: A- The Alagoas shelf. Set north of the São Francisco river with low fluvial input, dominance of SEC, recent organogenetic carbonate sediments with the calcareous algae Lithothamnium sp. and Halimeda sp. B- The São Francisco river alluvial fan and canyon. The river harbors a cascade of dams and after 1995, river flow declined by 40 % and was modulated to a constant flow of 2060 m3s-1, 95 % of the suspended matter load was retained within the reservoirs and nutrients (N,P) were impoverished by 90 % . The estuarine waters are now transparent and oligotrophic and the coastal plume lost its original turbidity and unimodal seasonal pattern of pulsation upon the shelf as indicated by In Situ sampling and Satellite imagery series (LANDSAT TM 2-5 and MODIS). The coastal plume is largely fed with suspended matter from resupension processes and coastal erosion. C- The Japaratuba river fan. The inner-mid shelf harbors relict muddy and sandy siliclastic sediments and the shelf margin biodetritic carbonates. Riverine inputs have become insignificant. D- The southern shelf of Sergipe. The muddy, sandy and carbonate Merl sediments are heterogeneously distributed,and the coast is affected by diffuse small riverine inputs and wash out by the SEC. Sedimentation rates (210Pbex chronology with the CRS model) of Domains B and C ranged between 0.7 and 0.1 cm year-1, being similar to those of the eastern Brazilian shelf.

Combined osteochondral allograft and meniscal allograft transplantation: a survivorship analysis.

PubMed

Getgood, Alan; Gelber, Jonathon; Gortz, Simon; De Young, Alison; Bugbee, William

2015-04-01

The efficacy of meniscal allograft transplantation (MAT) and osteochondral allografting (OCA) as individual treatment modalities for select applications is well established. MAT and OCA are considered symbiotic procedures due to a complementary spectrum of indications and reciprocal contraindications. However, few outcomes of concomitant MAT and OCA have been reported. This study is a retrospective review of patients who received simultaneous MAT and OCA between 1983 and 2011. Forty-eight (twenty-nine male: nineteen female) patients with a median age of 35.8 years (15-66) received combined MAT and OCA procedures between 1983 and 2011. Forty-three patients had received previous surgery with a median of 3 procedures (1-11 procedures). The underlying diagnosis was trauma (tibial plateau fracture) in 33 % with osteoarthritis predominating in 54.2 % of cases. Thirty-one patients received a lateral meniscus, 16 received a medial meniscus and one patient received bilateral MAT. The median number of OCAs was two per patient (1-5 grafts), with a median graft area of 15 cm(2) (0.7-41 cm(2)). There were 21 unipolar, 24 bipolar (tibiofemoral) and three multifocal lesions. Thirty-six MATs constituted a compound tibial plateau OCA with native meniscus attached. At follow-up, failure was defined as any procedure resulting in removal or revision of one or more of the grafts. Patients completed the modified Merle d'Aubigné and Postel (18-point) scale, Knee Society Function (KS-F) score, and subjective International Knee Documentation Committee (IKDC) scores. Patient satisfaction was also captured. Twenty-six of 48 patients (54.2 %) required reoperation, but only 11 patients (22.9 %) were noted to have failed (10 MAT and 11 OCA). The mean time to failure was 3.2 years (95 % CI 1.5-4.9 years) and 2.7 years (95 % CI 1.3-4.2 years) for MAT and OCA, respectively. The 5-year survivorship was 78 and 73 % for MAT and OCA respectively, and 69 and 68 % at 10 years. Six of the failures were in the OA cases and one was an OCD lesion where bipolar grafts were utilized. The OCD case underwent a revision OCA and remains intact. The others were converted to knee arthroplasty. One case failed due to early deep infection, ultimately requiring arthrodesis. Of those with grafts still intact, the mean clinical follow-up was 6.8 years (1.7-17.1 years). Statistically significant improvements in all outcome scores were noted between baseline and the latest follow-up. In total, 90 % of those responding would have the surgery again and 78 % were either extremely satisfied or satisfied with the outcome. The overall success rate of concomitant MAT and OCA was comparable with reported results for either procedure in isolation. A trend towards  a worse outcome was observed with bipolar tibiofemoral grafts in the setting of OA. Comparatively better results in less advanced, unipolar disease could suggest a benefit to early intervention that might merit a lower treatment threshold for combined MAT and OCA. IV.

Total hip arthroplasty survival in femoral head avascular necrosis versus primary hip osteoarthritis: Case-control study with a mean 10-year follow-up after anatomical cementless metal-on-metal 28-mm replacement.

PubMed

Ancelin, D; Reina, N; Cavaignac, E; Delclaux, S; Chiron, P

2016-12-01

Total hip arthroplasty is the most widely used procedure to treat avascular necrosis (AVN) of the femoral head. Few studies have compared the outcomes of THA in femoral head AVN and primary hip osteoarthritis. Therefore we performed a case-control study to compare THA for femoral head AVN vs. primary hip osteoarthritis in terms of: (1) prosthesis survival, (2) complication rates, (3) functional outcomes and radiographic outcomes, (4) and to determine whether specific risk factors for THA failure exist in femoral head AVN. THA survival is similar in femoral head AVN and primary hip osteoarthritis. We compared two prospective cohorts of patients who underwent THA before 65 years of age, one composed of cases with femoral head AVN and the other of controls with primary hip osteoarthritis. In both cohorts, a cementless metal-on-metal prosthesis with a 28-mm cup and an anatomical stem was used. Exclusion criteria were THA with other types of prosthesis, posttraumatic AVN, and secondary osteoarthritis. With α set at 5%, to obtain 80% power, 246 patients were required in all. Prosthesis survival was assessed based on time to major revision (defined as replacement of at least one implant fixed to bone) and time to aseptic loosening. The other evaluation criteria were complications, Postel-Merle d'Aubigné (PMA) score, and the Engh and Agora Radiographic Assessment (ARA) scores for implant osseointegration. The study included 282 patients, 149 with AVN and 133 with osteoarthritis. Mean age was 47.8±10.2 years (range, 18.5-65) and mean follow-up was 11.4±2.8 years (range, 4.5-18.3 years). The 10-year survival rates were similar in the two groups: for major revision, AVN group, 92.5% (95% confidence interval [95% CI], 90.2-94.8) and osteoarthritis group, 95.3% (95% CI, 92.9-97.7); for aseptic loosening, AVN group, 98.6% (95% CI, 97.6-98.6) and osteoarthritis, 99.2% (95% CI, 98.4-100). The AVN group had higher numbers of revision for any reason (19 vs. 6, P=0.018) and for dislocation (8 vs. 1, P=0.031). Mean PMA scores at last follow-up were comparable in the AVN group (17.65±1.27 [range, 10-18]) and osteoarthritis group (17.59±1.32 [range, 14-18]) (P=0.139). Osseointegration was also similar in the two groups: global Engh score, 26.51±1.81 (range, 14-27) for AVN and 26.84±0.91 (range, 19.5-27) for osteoarthritis (P=0.065); femoral ARA score, 5.83±0.46 (range, 3-6) for AVN and 5.90±0.42 (range, 3-6) for osteoarthritis (P=0.064); and cup ARA score, 5.74±0.67 (range, 3-6) for AVN and 5.78±0.66 (range, 3-6) for osteoarthritis (P=0.344). Survival in this study was good and consistent with recent data on AVN, with no difference between AVN and osteoarthritis. Revisions for any cause or for dislocation were more common after THA for AVN. Functional outcomes were similar in the AVN and osteoarthritis groups. An anatomical cementless prosthesis combined with metal-on-metal 28-mm bearing provides durable good outcomes. III, non-randomized comparison of two prospective cohorts. Published by Elsevier Masson SAS.

Treatment of sickle cell disease's hip necrosis by core decompression: a prospective case-control study.

PubMed

Mukisi-Mukaza, M; Manicom, O; Alexis, C; Bashoun, K; Donkerwolcke, M; Burny, F

2009-11-01

The young age of patients, total arthroplasties complications risks, and implant costs justify evaluation of the results of core decompression in the treatment of sickle-cell disease avascular necrosis of the femoral head (ONFH). In sickle-cell disease necrosis, core decompression offers good relief from pain and delays the use of total arthroplasty in comparison to a conservatively treated control group by a simple non-weight bearing protocol. From 1994 to 2008, among 215 drepanocytic adults, 42 patients (22 genotype SS, 20 genotype SC; 15 men, 27 women) presented symptomatic ONFH. We report the data from a prospective study of two patients' groups: a non-operated group (16 patients aged 36.5+/-6.5 years, 23 hips) and an operated group (26 patients aged 30.3+/-2.8 years, 42 hips). The results were considered on the basis of change in clinical status according to the numeric evaluation of pain scale, the functional score of Merle d'Aubigné-Postel (MAP), the radiological progression of lesions, and the time delay to total arthroplasty. Twenty-three hips were conservatively treated by discharge (a pair of canes). After a follow-up period of 13.4+/-0.5 years, no pain improvement was noted (p=0.76), and MAP score was unchanged (p=0.27). Out of 23 hips managed by discharge, 9 stage IV hips (degenerative arthritis, 39.1%) underwent arthroplasty after an average delay of 2.6+/-2.4 years. Forty-two hips were treated by core decompression. The duration of follow-up was 11.3+/-1.8 years. Postoperatively, pain reduction and MAP score improvement were significant in 39 out of 42 hips (93%, p<0.0001). Twenty-nine out of these 42 hips had a favorable evolution. Ten hips (23.8%) progressed to total arthroplasty, after a period of 7.4+/-2.7 years, longer than the one of the non-operated group (p=0.0007). By comparing the two groups (operated and non-operated), the benefit of core decompression appeared very significant (p<0.0001). In addition to allocating patients osteonecrosis stages, the Koo and Kim Index estimated the severity and evolution of necrotic lesions in both groups. It indicated decline in the non-operated group (p=0.002) and improvement for operated patients (p=0.0002). Core decompression had a favorable clinical and radiological outcome superior to surgical abstention. Stages I and II ONFH remained stable after drilling, necessitating no arthroplasty (considered as a failure of drilling). The Koo and Kim Index above 30 degrees in the non-operated group was a significant indicator of lesions degradation (p=0.002). In addition to the indolence obtained by core decompression, the benefit of drilling was manifested by the prolonging the adjournment before arthroplasty end-point. It was respectively 7.4+/-2.7 years in the operated group versus 2.6+/-2.4 years in the non-operated group (difference of 4.8 years, p<0.01). The technique of core decompression remains a valid option place in the treatment sickle-cell disease avascular necrosis of the femoral head (ONFH). It may be especially recommended in under-equipped regions where drepanocytosis and its osteo-articular complications are frequent. Level III case-control therapeutic study. 2009 Published by Elsevier Masson SAS.

Active Eruptions in the NE Lau Basin

NASA Astrophysics Data System (ADS)

Resing, J. A.; Embley, R. W.

2009-12-01

NE Lau Response Team: K Rubin, E Baker, J Lupton, M Lilley, T Shank, S Merle, R Dziak, T Collasius (Jason 2 Expedition Leader), N Buck, T Baumberger, D Butterfield, D Clague, D Conlin, J Cowen, R Davis, L Evans, J Huber, M Keith, N Keller, P Michael, E Podowski, A-L Reysenbach, K Roe, H Thomas, S Walker. During a May 2009 cruise to W Mata volcano in the NE Lau Basin, we made the first observations of an active eruption on the deep-sea floor. The cruise was organized after volcanic activity was detected at two sites (W Mata volcano and NE Lau Spreading Center, NELSC) during a Nov. 2008 NOAA-PMEL expedition. At that time, both sites had elevated H2 concentrations and volcaniclastic shards in the hydrothermal plumes. Moored hydrophone data since Jan 2009 indicate that the activity at W Mata has been continuous between these expeditions. Results of our cruise and other work suggest that the NE Lau Basin hosts an unusually high level of magmatic activity, making it an ideal location to study the effects of magmatic processes on hydrothermal activity and associated ecosystems. W Mata was visited with 5 ROV Jason 2 dives and 2 dives with the MBARI autonomous mapping vehicle in May 2009. It was actively erupting at the 1200 m deep summit during each, so a hydrophone was deployed locally to collect acoustic data. Ship and shore-based analysis of HD video, molten lava, rocks, sediments, hot spring waters, and micro- and macro biological specimens collected by Jason 2 have provided a wealth of data. The eruption itself was characterized by extrusion of red, molten lava, extensive degassing, formation of large magma bubbles, explosive pyroclast ejection, and the active extrusion of pillow lavas. The erupting magmas are boninite, a relatively rare magma type found only at convergent margins. The hydrothermal fluids are generally acidic and all diffuse fluids collected were microbially active, even those at pH <3. W Mata was host to shrimp similar to those found at several other submarine volcanoes including actively erupting NW Rota. Two dives were also conducted on the NELSC, which was no longer erupting and showed no signs of extensive eruption-related hydrothermal activity. A new lava flow was found beneath the Nov. 2008 zone of near-bottom water column temperature anomalies. Preliminary radiometric dating of lavas is consistent with a Nov. 2008 eruption. For >20 yrs the PMEL-Vents and NSF RIDGE programs have sought to observe active eruptions to understand their impacts and modes of occurrence, yet these dynamic events have been difficult to capture. This response cruise produced new insights on submarine volcanism, including the first documented back-arc spreading center eruption, the first boninitic eruption, and the first observation of pillow lava formation in the deep sea, arguably one of Earth’s most common surface rock forms. The “rapidity” with which we were able to return to these sites aided in this success. The cruise on the R/V TG Thompson was funded by NSF through the R2K, MARGINS, and MGG programs, and by NOAA Ocean Exploration and PMEL. Over 37 letters of interest were submitted from the scientific community to join the cruise and/or to receive samples, from which a multidisciplinary team of petrologists, fluid chemists, oceanographers, geophysicists, and macro- and micro- biologists was assembled.

Light-Curve Survey of Jupiter Trojan Asteroids

NASA Astrophysics Data System (ADS)

Duffard, R.; Melita, M.; Ortiz, J. L.; Licandro, J.; Williams, I. P.; Jones, D.

2008-09-01

Trojan asteroids are an interesting population of minor bodies due to their dynamical characteristics, their physical properties and that they are relatively isolated located at the snow-line The main hypotheses about the origin of the Jupiter Trojans assumed that they formed either during the final stages of the planetary formation (Marzari & Scholl 1998), or during the epoch of planetary migration (Morbidelli et al. 2005), in any case more than 3.8 Gy. ago. The dynamical configuration kept the Trojans isolated from the asteroid Main Belt throughout the history of the Solar System. In spite of eventual interactions with other populations of minor bodies like the Hildas, the Jupiter family comets, and the Centaurs, their collisional evolution has been dictated mostly by the intrapopulation collisions (Marzari et al. 1996, 1997). Therefore, the Jupiter Trojans may be considered primordial bodies, whose dynamical and physical properties can provide important clues about the environment of planetary formation. The available sample of Jupiter Trojans light-curves is small and mainly restricted to the largest objects. According to the MPC-website (updated last in March 2006), the present sample of rotation periods and light-curve-amplitudes of the Jupiter Trojan asteroids is composed by 25 objects with some information about their periods and by 10 of them with only an amplitude estimation. A survey of contact binary Trojan asteroids has been done by Mann et al. 2007, where they have recorded more than 100 amplitudes from sparse-sampled light-curves and very-wellresolved rotational periods. More than 2000 Trojan asteroids have been discovered up to date, so, there is an urgent need to enlarge the sample of intrinsic rotation periods and accurate light-curve amplitudes and to extend it to smaller sizes. Results and Discusions We requested 26 nights of observation in the second semester of 2007, to begin with the survey. They were scheduled for the following instruments: the WFC, Isaac Newton Telescope (ING, 2.5m, 7 nights), CAHA (2.2m, 6 nights), CCD direct OSN (1.5m, 6 nights) and CCD direct, JS (CASLEO, 2.15m, 7 nights). From these observations we have constructed the differential photometry light-curves of 15 Trojan asteroids. Plots showing the actual light curves and the quality assessment of our estimation of the rotational period can be downloaded from: http://www.df.uba.ar/users/melita/PICT07/PICT07.ht ml. See table 1 for the main results. In figure 1 we show the known periods of the Trojan asteroids as a function of their size. Some of these data are still of poor quality. It remains to be confirmed the reality of the clustering of small objects at small periods, so, there is a need to improve those rotation rates with reliable standard photometry produced at an instrument of larger aperture. Also, a lack of data for the biggest objects is apparent from this figure. In figure 2 we show a plot of the Rmagnitude amplitude variation as a function of the absolute magnitude. Most of the objects are from the survey of contact binaries by Mann et al. 2007. This plot seems to indicate that the extreme elongations recorded previously are constrained to the largest objects. Our data follows the trend of a negative slope, but given the error-bars involved, it remains to be confirmed if smaller objects tend to be more spherical.

Sugar beet growth in a changing climate: past, present and future trends in southwest Germany

NASA Astrophysics Data System (ADS)

Kremer, Pascal; Fuchs, Hans-Joachim; Lang, Christian

2017-04-01

In the study, single factors and their impact on sugar beet cultivation against the background of past and projected climate change are being analyzed. The database consists of climate data by the German Weather Service and 1x1 km interpolated INTERMET raster data. Impact models were run to assess possible future trends using climate projection data of the REgional MOdel (REMO), emission scenario A1B, Run 1, data stream 2 for Germany, daily resolution, without bias correction, 10x10 km raster (n=150) (MPI on behalf of UBA 2006). Compared periods were: B:1971 2000; K:2021-2050; L:2071-2100. Agronomic data were collected from the field books of regional trials from 1974 2014 (n=448). Moreover, a business survey of regional farmers was carried out and evaluated. Impact models to predict timing for sowing, the date of field emergence and row closure, were derived from these data. The ontogenesis was simulated using a linear, temperature-based leaf-growth model. Sowing shifted forward by 7,3 days in regional field trials from 1974 2014. Progress-oriented, risk-tolerant farmers start sowing 10-14 days earlier compared to 1980. Recently, sowing is being conducted on average on 21 March in southwest Germany. For period K, 17 March, and for period L, 2 March is being projected as the average future sowing date while the same late frost risk applies compared to present climatic conditions. Shifting forward the sowing date with spring warming and, thus, exploiting the associated yield potential is the most promising agronomic adaptation strategy to the projected climate change on the farm level. In connection to earlier sowing, the field emergence tendentially shifted forward by 14 days in the field trials. Assuming sowing on 15 March, projection results show an advance of field emergence form 7 April in period B to 3 April in period L. Row closure in field trials in average shifted forward by 19,6 days. For period L, 29 May and thus, an earlier row closure of 9 days compared to K, is being projected. In period L, 20-leaf-stage is being projected 7,8 days, and 40-leaf-stage 11,2 days earlier compared to period K. All previously mentioned trends positively influence the yield potential of sugar beets due to the increasing use efficiency of photosynthetically active radiation. Running a correlation analysis, the height of the yield variance reconnaissance ratio of the main weather-related growth factors, temperature and precipitation, was determined. During the main growth phase from June-September, the precipitation sum explains 76%, the daily average temperature sum from April-October in the range of 3°C-19°C explains 64% of the yield variance of Mainz from 1991-2012. For both parameters, a decrease is being projected for the second half of the 21st century, which would influence the regional yield potential negatively. Summarizing, climate change had positive as well as negative impacts on regional sugar beet cultivation. Based on the REMO data, past trends continue prospectively. Due to that, it is important to fully use positive effects for yield formation. Furthermore, adaption to negative climatic changes and research are crucial to guarantee a high-yielding, sustainable sugar beet growth in future.

Abridged version of the AWMF guideline for the medical clinical diagnostics of indoor mould exposure: S2K Guideline of the German Society of Hygiene, Environmental Medicine and Preventive Medicine (GHUP) in collaboration with the German Association of Allergists (AeDA), the German Society of Dermatology (DDG), the German Society for Allergology and Clinical Immunology (DGAKI), the German Society for Occupational and Environmental Medicine (DGAUM), the German Society for Hospital Hygiene (DGKH), the German Society for Pneumology and Respiratory Medicine (DGP), the German Mycological Society (DMykG), the Society for Pediatric Allergology and Environmental Medicine (GPA), the German Federal Association of Pediatric Pneumology (BAPP), and the Austrian Society for Medical Mycology (ÖGMM).

PubMed

Wiesmüller, Gerhard A; Heinzow, Birger; Aurbach, Ute; Bergmann, Karl-Christian; Bufe, Albrecht; Buzina, Walter; Cornely, Oliver A; Engelhart, Steffen; Fischer, Guido; Gabrio, Thomas; Heinz, Werner; Herr, Caroline E W; Kleine-Tebbe, Jörg; Klimek, Ludger; Köberle, Martin; Lichtnecker, Herbert; Lob-Corzilius, Thomas; Merget, Rolf; Mülleneisen, Norbert; Nowak, Dennis; Rabe, Uta; Raulf, Monika; Seidl, Hans Peter; Steiß, Jens-Oliver; Szewszyk, Regine; Thomas, Peter; Valtanen, Kerttu; Hurraß, Julia

2017-01-01

This article is an abridged version of the AWMF mould guideline "Medical clinical diagnostics of indoor mould exposure" presented in April 2016 by the German Society of Hygiene, Environmental Medicine and Preventive Medicine ( Gesellschaft für Hygiene, Umweltmedizin und Präventivmedizin, GHUP ), in collaboration with the above-mentioned scientific medical societies, German and Austrian societies, medical associations and experts. Indoor mould growth is a potential health risk, even if a quantitative and/or causal relationship between the occurrence of individual mould species and health problems has yet to be established. Apart from allergic bronchopulmonary aspergillosis (ABPA) and mould-caused mycoses, only sufficient evidence for an association between moisture/mould damage and the following health effects has been established: allergic respiratory disease, asthma (manifestation, progression and exacerbation), allergic rhinitis, hypersensitivity pneumonitis (extrinsic allergic alveolitis), and increased likelihood of respiratory infections/bronchitis. In this context the sensitizing potential of moulds is obviously low compared to other environmental allergens. Recent studies show a comparatively low sensitizing prevalence of 3-10% in the general population across Europe. Limited or suspected evidence for an association exist with respect to mucous membrane irritation and atopic eczema (manifestation, progression and exacerbation). Inadequate or insufficient evidence for an association exist for chronic obstructive pulmonary disease, acute idiopathic pulmonary hemorrhage in children, rheumatism/arthritis, sarcoidosis and cancer. The risk of infection posed by moulds regularly occurring indoors is low for healthy persons; most species are in risk group 1 and a few in risk group 2 ( Aspergillus fumigatus, A. flavus ) of the German Biological Agents Act ( Biostoffverordnung ). Only moulds that are potentially able to form toxins can be triggers of toxic reactions. Whether or not toxin formation occurs in individual cases is determined by environmental and growth conditions, above all the substrate. In the case of indoor moisture/mould damage, everyone can be affected by odour effects and/or mood disorders. However, this is not a health hazard. Predisposing factors for odour effects can include genetic and hormonal influences, imprinting, context and adaptation effects. Predisposing factors for mood disorders may include environmental concerns, anxiety, condition, and attribution, as well as various diseases. Risk groups to be protected particularly with regard to an infection risk are persons on immunosuppression according to the classification of the German Commission for Hospital Hygiene and Infection Prevention ( Kommission für Krankenhaushygiene und Infektionsprävention, KRINKO ) at the Robert Koch- Institute (RKI) and persons with cystic fibrosis (mucoviscidosis); with regard to an allergic risk, persons with cystic fibrosis (mucoviscidosis) and patients with bronchial asthma should be protected. The rational diagnostics include the medical history, physical examination, and conventional allergy diagnostics including provocation tests if necessary; sometimes cellular test systems are indicated. In the case of mould infections the reader is referred to the AWMF guideline "Diagnosis and Therapy of Invasive Aspergillus Infections". With regard to mycotoxins, there are currently no useful and validated test procedures for clinical diagnostics. From a preventive medicine standpoint it is important that indoor mould infestation in relevant dimension cannot be tolerated for precautionary reasons. With regard to evaluating the extent of damage and selecting a remedial procedure, the reader is referred to the revised version of the mould guideline issued by the German Federal Environment Agency ( Umweltbundesamt, UBA ).

Unique Project of Single-Cutting Head Longwall Shearer Used for Thin Coal Seams Exploitation / Projekt Jednoorganowego Kombajnu ŚCIANOWEGO O Specjalnej Konstrukcji Przeznaczonego do Eksploatacji POKŁADÓW Cienkich

NASA Astrophysics Data System (ADS)

Bołoz, Łukasz

2013-12-01

Problem of thin hard coal seams exploitation, including chosen data related with their resources in Poland, has been discussed in the introduction of the present study. On the basis of actually operated machines the assumptions, which should be satisfied by the longwall shearer used for exploitation of thin hard coal seams, have been made. A project of such longwall shearer combined with band conveyor and mechanized longwall support, including description of the machine operation technology and analysis of possible day output achievement, have been presented. Polska dysponuje stosunkowo dużymi zasobami surowców energetycznych, a ciągle rosnące zapotrzebowanie na energię skłania do ich racjonalnego wykorzystywania. Jedną z możliwości takiego racjonalnego gospodarowania zasobami naturalnymi jest eksploatacja węgla kamiennego z pokładów cienkich. W związku z wybieraniem coraz cieńszych pokładów węgla, zalegających bardzo głęboko, w trudnych warunkach górniczo-geologicznych napotyka się na duże problemy związane z uzyskaniem wymaganej wydajności wydobycia przy użyciu stosowanych aktualnie metod. Przyjmuje się, ze pokłady cienkie to takie o miąższości od 1.0 m do 1.5 m i właśnie ta niewielka wysokość wyrobiska ścianowego powoduje szereg ograniczeń związanych z efektywną eksploatacją węgla. Na podstawie dostępnych danych określono, że ilości węgla kamiennego w cienkich pokładach wynosi około 600 mln Mg. Znaczna część pokładów cienkich w ostatnich latach została przeklasyfikowana na nieprzemysłowe, co pozwala stwierdzić, że rzeczywista ilość węgla w pokładach cienkich jest znacznie większa. Na podstawie analizy wad i zalet jak i danych technicznych produkowanych obecnie maszyn, określono wytyczne i założenia do nowego rozwiązania maszyny urabiającej przeznaczonej do wydobywania węgla w ścianach niskich. Kombajn do eksploatacji cienkich pokładów powinien spełniać następujące wymagania (Bołoz, 2012): • praca w systemie ścianowym, • zastosowanie frezowania jako metody skrawania, • rozdzielenie procesu frezowania od procesu ładowania, • zastosowanie pełnej automatyzacja pracy, • zastosowanie cięgnowego systemu posuwu, • możliwość rozpoczynania nowego skrawu bez konieczności zawrębiania, • gabaryty dostosowane do pracy w ścianach o wysokości od 1.0 m do 1.6 m, praca systemem dwukierunkowym. Fig. 2 przedstawia koncepcję kombajnu jednoorganowego. Kombajn ten składa się z kadłuba 2, jednego zamocowanego centralnie organu urabiającego 1 oraz dwóch rozkładanych ładowarek odkładniowych 3 i 4. Ładowarka 3 znajduje się w pozycji czynnej, natomiast ładowarka 4 w biernej. Kombajn jest ciągnięty po rynnach przenośnika 5 za pomocą łańcucha 6. Łańcuch 7 jest gałęzią bierną dla przedstawionego zwrotu prędkości. Podane, orientacyjne wymiary wynikają z analizy dotychczasowych rozwiązań kombajnów, głowic strugowych oraz założonego zakresu wysokości wyrobiska ścianowego (Krauze, 2006; Bołoz, 2012). Dla zaproponowanego rozwiązania przyjęto szereg koniecznych wielkości i przeprowadzono analizę możliwego do uzyskania wydobycia dobowego. Zestawione tabelarycznie wyniki umożliwiają określenie wydobycia dobowego możliwego do uzyskania przy określonych wartościach parametrów geometrycznych ściany, kinematycznych kombajnu oraz organizacyjnych pracy ściany. Dla założonych parametrów można stwierdzić, że minimalne wydobycie dobowe na poziomie Vd = 4032 Mg/d uzyskano dla L = 180 m, tp = 11 min, H = 1.0 m oraz T = 12 h/d. Maksymalne wydobycie dobowe na poziomie Vd = 11 612 Mg/d uzyskać można dla L = 300 m, tp = 0 min, H = 1.6 m oraz T = 18 h/d. Na wydobycie dobowe największy wpływ ma dobowy czas pracy ściany a następnie czas przekładki (Bołoz, 2012). Średnica organu dla takiego kombajnu dobierana jest do grubości pokładu. W przedmiotowym rozwiązaniu przyjęto organ o konstrukcji przestrzennej (belki nożowe zamiast płatów), aby powstający podczas frezowania urobek mógł spadać na spąg (Krauze, 2012b). Przykładowe rozwiązanie organu przestrzennego przedstawia fig. 3. Funkcję ładowania, realizowaną normalnie przez płaty, przejmują ładowarki. Rozdzielenie procesu ładowania od procesu frezowania jest jedną z najważniejszych zalet prezentowanego rozwiązania. Podczas pracy w ścianie parametry kinematyczne kombajnu mogą być zwiększane bez ryzyka wystąpienia problemów z ładowaniem na przenośnik, co obok możliwości ruchowych kombajnisty było głównym czynnikiem hamującym wzrost wydobycia. Załadunek urobku na przenośnik odbywa się za pomocą ładowarki, która po zmianie kierunku urabiania składa się, natomiast druga ustawiana jest w pozycji roboczej (Krauze, 2010). Kombajn porusza się tradycyjnie po rynnie przenośnika, jednak przy zastosowaniu cięgnowego systemu posuwu, który zrealizowany jest za pomocą napędów znajdujących się w chodnikach. Rozwiązanie takie umożliwia znaczne zmniejszenie gabarytów kombajnu dzięki usunięciu ciągników z kadłuba. Należy zaznaczyć, że w prezentowanym rozwiązaniu zakłada się zastosowanie pełnej automatyzacja pracy kombajnu i pozostałych maszyn ścianowych, co pozwala na urabianie calizny bez obecności załogi bezpośrednio w wyrobisku. Ma to duże znaczenie dla możliwości zwiększenia prędkości posuwu, szczególnie przy zakresie wysokości 1.0 m÷1.6 m. Przy wykorzystaniu znanych, z rozwiązań strugowych, systemów automatyki, sterowania i diagnostyki wprowadzenie automatyzacji procesu nie będzie stanowiło znaczącego problemu. W proponowanym rozwiązaniu kombajn ma możliwość wyjechania do chodnika na tyle, aby możliwe było zrealizowanie przekładki jak w przypadku strugów. Uzyskuje się wtedy krótki czas przekładki, który w skrajnym przypadku może zmieścić się w tzw. czasie organizacyjnym ściany. Ponadto urabianie odbywa się pełnym zabiorem na całej długości ściany co również korzystnie wpływa na wydobycie. Przekładkę realizować będą, oprócz układów przesuwnych sekcji, układy przesuwne napędów zlokalizowane w chodnikach lub ewentualnie obudowa skrzyżowań. Do sterowania położeniem kombajnu jednoorganowego, a w szczególności kierunkiem eksploatacji na wybiegu ściany (wznios, upad), zastosowane będą siłowniki korekcyjne łączące belkę układu przesuwnego sekcji z rynną przenośnika. Kopalnie jak i producenci sprzętu górniczego wykazują coraz większe zainteresowanie możliwością skutecznej eksploatacji pokładów cienki. Zaproponowany kompleks do eksploatacji cienkich pokładów wyposażony w kombajn jednoorganowy przeznaczony jest do pracy w technologii urabiania dwukierunkowego. Charakterystyczną cechą tej technologii jest brak fazy zawrębiania oraz praca na pełny zabiór na całej długości ściany. W przypadku zmiany grubości pokładu możliwa jest zmiana organu, natomiast sterowanie w kierunku wybiegu odbywać się będzie za pomocą siłowników korekcyjnych. Opracowanie technologii pracy kompleksu wyposażonego w kombajn jednoorganowy, analiza możliwego do osiągnięcia wydobycia dobowego, przy jego zastosowaniu oraz określenie wymaganych parametrów maszyn kompleksu ścianowego, a w szczególności kombajnu, potwierdza poprawność przyjętych założeń.

ROBUST hot wire probe efficiency for total water content measurements in glaciated conditions

NASA Astrophysics Data System (ADS)

Leroy, Delphine; Lilie, Lyle; Weber, Marc; Schwarzenboeck, Alfons; Strapp, J. Walter

2017-04-01

During the two High Altitude Ice Crystals (HAIC, Dezitter et al. 2013)/High Ice Water Content (HIWC, Strapp et al., 2016a) international flight campaigns that investigated deep convection in the tropics, the French Falcon 20 research aircraft was equipped with two different devices measuring the Total Water Content (TWC): - the IKP-2 (Isokinetic Probe, Davison et al. 2008, 2016), - and the hot wire ROBUST probe (Strapp et al. 2008; Grandin et al. 2014). The IKP-2 probe is an evaporator that has been specifically designed to measure high ice water content (Strapp et al. 2016b) with a collection efficiency near unity. It has undergone extensive performance assessment in liquid and glaciated conditions in several wind tunnels. The Robust probe was initially developed by Science Engineering Associates to estimate high ice water content in a high speed wind tunnel, in harsh conditions where other hot-wires had been observed to suffer failures. It was known at the outset that, like other hot-wire TWC probes, it would measure only a quasi-constant fraction of the true ice water content. Early wind tunnel and flight experience with the ROBUST probe revealed that this fraction was the order of 40% for ice crystals. During the HAIC/HIWC campaigns (Leroy et al. 2016, 2017), supercooled liquid water conditions were documented according to a detailed analysis of a Rosemount Ice detector (RICE) and a Cloud Droplet Probe (CDP) measurements, and were found to be rare. Thus, the HAIC/HIWC dataset represents a unique opportunity to study in more detail the ROBUST efficiency in glaciated conditions, using the IKP-2 values as a comparative reference. Comparison of IKP-2 and ROBUST measurements will show that the ROBUST behavior differs between low (below 1.5 g/m3) and high (above 2 g/m3) ice content conditions and is also sensitive to temperature. The sensitivity of the ROBUST collection efficiency to ice particles size could also be explored as optical imaging probes were part of the airborne instrument package but no clear trend has been highlighted for the moment. References : Davison, C., J. MacLeod, J. Strapp, and D. Buttsworth, 2008: Isokinetic Total Water Content Probe in a Naturally Aspirating Configuration: Initial Aerodynamic Design and Testing. 46th AIAA Aerospace Sciences Meeting and Exhibit, American Institute of Aeronautics and Astronautics http://arc.aiaa.org/doi/abs/10.2514/6.2008-435 (Accessed February 9, 2015). Davison, C. R., J. W. Strapp, L. E. Lilie, T. P. Ratvasky, and C. Dumont, 2016: Isokinetic TWC Evaporator Probe: Calculations and Systemic Error Analysis. American Institute of Aeronautics and Astronautics http://arc.aiaa.org/doi/10.2514/6.2016-4060 (Accessed July 29, 2016). Dezitter, F., A. Grandin, J.-L. Brenguier, F. Hervy, H. Schlager, P. Villedieu, and G. Zalamansky, 2013: HAIC - High Altitude Ice Crystals. 5th AIAA Atmospheric and Space Environments Conference, American Institute of Aeronautics and Astronautics http://arc.aiaa.org/doi/abs/10.2514/6.2013-2674 (Accessed February 9, 2015). Grandin, A., J.-M. Merle, M. Weber, J. Strapp, A. Protat, and P. King, 2014: AIRBUS Flight Tests in High Total Water Content Regions. American Institute of Aeronautics and Astronautics http://arc.aiaa.org/doi/abs/10.2514/6.2014-2753 (Accessed March 8, 2016). Leroy, D., and Coauthors, 2016: HAIC/HIWC field campaigns - Specific findings on ice crystals characteristics in high ice water content cloud regions. American Institute of Aeronautics and Astronautics http://arc.aiaa.org/doi/10.2514/6.2016-4056 (Accessed January 10, 2017). Leroy, D., and Coauthors, 2017: Ice Crystal Sizes in High Ice Water Content Clouds. Part II: Statistics of Mass Diameter Percentiles in Tropical Convection Observed during the HAIC/HIWC Project. J. Atmospheric Ocean. Technol., 34, 117-136, doi:10.1175/JTECH-D-15-0246.1. Strapp, J. W., J. MacLeod, and L. Lilie, 2008: Calibration of ice water content in a wind tunnel/engine test cell facility. 15th Intl. Conf. on Cloud and Precipitation http://cabernet.atmosfcu.unam.mx/ICCP-2008/abstracts/Program_on_line/Poster_13/StrappEtAl-extended.pdf (Accessed April 25, 2016). Strapp, J. W., L. E. Lilie, T. P. Ratvasky, C. R. Davison, and C. Dumont, 2016b: Isokinetic TWC Evaporator Probe: Development of the IKP2 and Performance Testing for the HAIC-HIWC Darwin 2014 and Cayenne Field Campaigns. American Institute of Aeronautics and Astronautics http://arc.aiaa.org/doi/10.2514/6.2016-4059 (Accessed July 29, 2016). Strapp, J. W., G. A. Isaac. A. Korolev, T. Ratvasky, R. Potts, P. May, A. Protat, P. Minnis, A. Ackerman, A. Fridlind, J. Haggerty, and J. Riley, 2016a: The High Ice Water Content (HIWC) Study of deep convective clouds: Science and technical plan. FAA Rep. DOT/FAA/TC-14/31, available at http://www.tc.faa.gov/its/worldpac/techrpt/tc14-31.pdf. 105 pgs.

Modeling of the impact of Rhone River nutrient inputs on the dynamics of planktonic diversity

NASA Astrophysics Data System (ADS)

Alekseenko, Elena; Baklouti, Melika; Garreau, Pierre; Guyennon, Arnaud; Carlotti, François

2014-05-01

Recent studies devoted to the Mediterranean Sea highlight that a large number of uncertainties still exist particularly as regards the variations of elemental stoichiometry of all compartments of pelagic ecosystems (The MerMex Group, 2011, Pujo-Pay et al., 2011, Malatonne-Rizotti and the Pan-Med Group, 2012). Moreover, during the last two decades, it was observed that the inorganic ratio N:P ratio in among all the Mediterranean rivers, including the Rhone River, has dramatically increased, thus strengthening the P-limitation in the Mediterranean waters (Ludwig et al, 2009, The MerMex group, 2011) and increasing the anomaly in the ratio N:P of the Gulf of Lions and all the western part of NW Mediterranean. At which time scales such a change will impact the biogeochemical stocks and fluxes of the Gulf of Lion and of the whole NW Mediterranean sea still remains unknown. In the same way, it is still uncertain how this increase in the N:P ratio will modify the composition of the trophic web, and potentially lead to regime shifts by favouring for example one of the classical food chains of the sea considered in Parsons & Lalli (2002). To address this question, the Eco3M-MED biogeochemical model (Baklouti et al., 2006a,b, Alekseenko et al., 2014) representing the first trophic levels from bacteria to mesozooplankton, coupled with the hydrodynamical model MARS3D (Lazure&Dumas, 2008) is used. This model has already been partially validated (Alekseenko et al., 2014) and the fact that it describes each biogenic compartment in terms of its abundance (for organisms), and carbon, phosphorus, nitrogen and chlorophyll (for autotrophs) implies that all the information on the intracellular status of organisms and on the element(s) that limit(s) their growth will be available. The N:P ratios in water, organisms and in the exported material will also be analyzed. In practice, the work will first consist in running different scenarios starting from similar initial early winter conditions (for which the sea surface layer is well mixed). As a first step, these scenarios will allow to investigate the impact of changes in the N:P ratios of the Rhone River on the structure of the planktonic community at short time scale (two years). Acknowledgements The present research is a contribution to the Labex OT-Med (n° ANR-11-LABX-0061) funded by the French Government «Investissements d'Avenir» program of the French National Research Agency (ANR) through the A*MIDEX project (n° ANR-11-IDEX-0001-02). We thank our collegue P. Raimbault for the access to the MOOSE project dataset about the nutrient composition of the Rhone River . References Alekseenko E., Raybaud V., Espinasse B., Carlotti F., Queguiner B., Thouvenin B., Garreau P., Baklouti M. (2014) Seasonal dynamics and stoichiometry of the planktonic community in the NW Mediterranean Sea: a 3D modeling approach. Ocean Dynamics IN PRESS. http://dx.doi.org/10.1007/s10236-013-0669-2 Baklouti M, Diaz F, Pinazo C, Faure V, Quequiner B (2006a) Investigation of mechanistic formulations depicting phytoplankton dynamics for models of marine pelagic ecosystems and description of a new model. Prog Oceanogr 71:1-33 Baklouti M, Faure V, Pawlowski L, Sciandra A (2006b) Investigation and sensitivity analysis of a mechanistic phytoplankton model implemented in a new modular tool (Eco3M) dedicated to biogeochemical modelling. Prog Oceanogr 71:34-58 Lazure P, Dumas F (2008) An external-internal mode coupling for a 3D hydrodynamical model for applications at regional scale (MARS). Adv Water Resour 31(2):233-250 Ludwig, W., Dumont, E., Meybeck, M., Heussner, S. (2009). River discharges of water and nutrients to the Mediterranean and Black Sea: Major drivers for ecosystem changes during past and future decades? Progress in Oceanography 80, pp. 199-217 Malanotte-Rizoli, P. and Pan-Med Group. (2012) Physical forcing and physical/biochemical variability of the Mediterranean Sea : A review of unresolved issues and directions of future research. Report of the Workshop «Variability of the Eastern and Western Mediterranean circulation and termohaline properties : similarities and differences ». Rome, 7-9 November, 2011, 48 pp. Parsons, T. R., and Lalli, C. M. (2002) Jellyfish population explosions: Revisiting a hypothesis of possible causes. La Mer 40: 111-121. Pujo-Pay, M., Conan, P., Oriol L., Cornet-Barthaux, V., Falco, C., Ghiglione, J.-F., Goyet, C., Moutin, T. and Prieur, L. (2011) Integrated survey of elemental stoichiometry (C, N, P) from the western to eastern Mediterranean Sea, Biogeoscciences, 8, 883-899. The MerMex Group, Durrieu de Madron X, Guieu C, Sempéré R, Conan P, Cossa D, D'Ortenzio F, Estournel C, Gazeau F, Rabouille C, Stemmann L, Bonnet S, Diaz F, Koubbi P, Radakovitch O, Babin M, Baklouti M, Bancon-Montigny C, Belviso S, Bensoussan N, Bonsang B, Bouloubassi I, Brunet C, Cadiou J-F, Carlotti F, Chami M, Charmasson S, Charrière B, Dachs J, Doxaran D, Dutay J-C, Elbaz-Poulichet F, Eléaume M, Eyrolles F, Fernandez C, Fowler S, Francour P, Gaertner JC, Galzin R, Gasparini S, Ghiglione J-F, Gonzalez J-L, Goyet C, Guidi L, Guizien K, Heimbürger L-E, Jacquet SHM, Jeffrey WH, Joux F, Le Hir P, Leblanc K, Lefèvre D, Lejeusne C, Lemé R, Loÿe-Pilot M-D, Mallet M, Méjanelle L,Mélin F, Mellon C, Mérigot B, Merle P-L, Migon C, Miller WL, Mortier L, Mostajir B, Mousseau L, Moutin T, Para J, Pérez T, Petrenko A, Poggiale J-C, Prieur L, Pujo-Pay M, Pulido-Villena, Raimbult P, Rees AP, Ridame C, Rontani J-F, Ruiz Pino D, Sicre MA, Taillandier V, Tamburini C, Tanaka T, Taupier-Letage I, Tedetti M, Testor P, Thébault H, Thouvenin B, Touratier F, Tronczynski J, Ulses C, Van Wambeke F, Vantrepotte V, Vaz S, Verney R (2011) Marine ecosystems' responses to climatic and anthropogenic forcings in the Mediterranean. Prog Oceanogr 91:97-166

Control of the geomorphic evolution of an active crater: Popocatpetl (Mexico) 1994-2003.

NASA Astrophysics Data System (ADS)

Andrés, N.; Zamorano, J. J.; Palacios, D.; Macias, J. L.; Sanjosé, J. J.

2009-04-01

Volcanic activity often causes intense and successive geomorphic changes to occur inside a crater. In terms of hazard mitigation, it is important to understand the cause of these changes whether they be exterior lava spills, sequences of explosions or massive glacier melt. Access to an active crater, however, is very difficult and dangerous, so analytical approaches involving remote study must substitute actual fieldwork. Several studies done at Popocatepetl volcano during its most recent eruptive phase that began in December 1994, use remote techniques and are described in Cruz-Reyna et al. (1998), Wright et al. (2002), Martín-Del Pozo et al. (2003), Tanarro et al. (2005), Matiella et al. (2008), and Zamorano et al. (1996,1998), among others. The compendium of results reveals that recent volcanic activity on Popocatépetl is characterized by successive dome growth and destruction inside the crater. Macias and Siebe (2005) even suggest that the walls of the crater may no longer withstand future dome growth. The purpose of this study is to understand the morphologic evolution of the interior of the crater during the most active period of the present eruptive phase on Popocatepetl from 1994 to 2003. The methodology is based on photogrammetry techniques that have been used successfully at volcanic sites by Donnadieu et al. (2003), and on a GIS to organize information, draft maps and 3-D images, and to calculate spatial variations in landforms (Procter et al., 2006; Schilling et al., 2006). Traditional aerial photo interpretation was used for 22 triplets selected from a collection of photos taken by the Mexican Highway and Transport Secretariat, from 1982 to 2003, and enabled us to draft geomorphic maps of the interior of the crater. The photos and maps were rectified and georeferenced with ArcGis software, and then the maps were digitized. The areas containing morphologic units associated with a date (exterior crater walls, colluvial ramps and recent volcanic complex features such as craters, cones and domes) were uploaded to a temporal database. Next, we linked the morphologic description of the craters and the surface variations occupied by each of the landforms with the volcanic activity. Topographic restitution for 7 of the 22 pairs of selected aerial photos was performed and the Digital Elevations Models (DEMs) for each date were imported to ArcGis to analyze the variations in elevation at the base of the crater and changes on the slopes. Finally, we calculated the free space inside the crater for each date. The results from the data processing showed a sequence of transformations in the crater, each of which was identified with a specific type and intensity of volcanic activity. In the pre-eruptive stage prior to 1994, the growth of the outer walls and the colluvial ramp of the crater (90% of the crater) was attributed primarily to non-volcanic activity. The period from 1994 to June 1999, was marked by dome growth and destruction, which expanded the surface area of the complex (34.5% in April 1998), but reduced the colluvial ramp and the wall. Explosions ejected material from inside the crater, increasing its width and depth (48m). Free space occupied 17.3x106 m3 in June1999, but after an interval of relative calm, dome growth resumed in 2000. Larger forms were produced and were not immediately destroyed, so the dome complex increased to 45.219 m2 by September 2001. This chain of events marked by the overlapping of domes and materials, gave the recent volcanic complex an intricate morphology. During this time, the depth of the crater in February 2003 was 66 m with 11.2x106 m3 of free space. The July-August 2003 photograms reveal a morphology of craters created by a succession of phreatomagmatic explosions that inhibited the formation of lava bodies. Judging from descriptions by volcanologists in February 2004 (Macias and Siebe, 2005), the amount of material ejected from the crater by these explosions was not substantial. References.- Cruz-Reyna, S. de la; Meli, R.; Macías, J.L.; Castillo, F.; & Cabrera, B., 1998. Cyclical dome extrusions that by late 1997 filled one-third of crater capacity, In Smithsonian-GVP Monthly Reports, Popocatépetl, Smithsonian Institution. Bull. Glob. Volcanism Netw, (GVN) 23 (2), 2 - 4. Donnadieu, F.; Kelfoun, K.; Van Wyk de Vries, B.; Decchi, E.; & Merle, O., 2003. Digital photogrammetry as a tool in analogue modelling: applications to volcano instability, Journal of Volcanology and Geothermal Research, 123 (1-2), 161-180. Macías, J.L. & Siebe, C., 2005. Popocatépetl crater filled to the brim: significance for hazard evaluation, Journal of Volcanology and Geothermal Research (141) 327-330. Martín-Del Pozzo, A.L.; Cifuentes-Nava, G.; Cabral-Cano, E.; Bonifaz, F.; Correa, I.; & Mendiola, I.F., 2003. Timing magma ascent at Popocatepetl Volcano, Mexico, 2000-2001, Journal of Volcanology and Geothermal Research ,125, 107-120. Matiella, M.A.; Watson, I.M.; Delgado, H.; Rose, W.I.; , Cárdenas, L.; & Realmuro, V.J., 2008, Volcanic emissions from Popocatépetl volcano, Mexico, quantified using Moderate Resolution Imaging Spectroradiometer (MODIS) infrared data: A case study of the December 2000-January 2001 emissions, Journal of Volcanology and Geothermal Research, 170, 1-2, 76-85. Procter, J.N.; Platz, T.; & Cronin, S.J., 2006. A remnant summit lava dome and its influence on future eruptive hazards, Geophysical Research Abstracts, Vol. 8, 10211. Schilling, S.P.; Ramsey, D.W.; Messerich, J.A.; & Thompson, R.A., 2006. Map: Rebuilding Mount St. Helens. U.S. Geological Survey Scientific Investigations Map 2928. Tanarro, L. M.; Zamorano, J.J.; & Palacios, D., 2005. Glacier degradation and lahar formation on the Popocatépetl volcano (Mexico) during the last eruptive period (1994-2003), Zeitschrift Geomorphologie (140) 73-92. Zamorano, J.J., Gómez, A. 1996 "Análisis geomorfoloógico a detalle,1:10 000 del cráter del volcán Popocatépetl (1989-1996)" IV Reunión Nacional de Geomorfología. Pátzcuaro, Michoacán. México. Zamorano, JJ. Goméz, A. y Martín del Pozo, A. L. 1998 "Cartografía geomorfológica del cráter del volcán Popocatépetl (Esc. 1:10 000): mayo 1989-abril 1998" Primera Reunión Nacional de Ciencias de la Tierra. D.F. México. Wright, R.; Cruz-Reyna, S. de la; Harris, A.; Flynn, L.; & Gomez-Palacios, J.J., 2002. Infrared satellite monitoring at Popocatépetl: Explosions, exhalations, and cycles of dome growth, Journal of Geophysical Research, 107(B8), 2153.

Obituary: John P. Oliver (1939-2011)

NASA Astrophysics Data System (ADS)

Cohen, Howard

2011-12-01

John P. Oliver, an emeritus professor of astronomy at the University of Florida in Gainesville, passed away Thursday, February 10, 2011, after a courageous and long battle with renal cancer. He left behind memories of a life and career to envy. During his forty years of service to his profession and department, this unique astronomer distinguished himself as a research scientist and instrumentalist, creative software designer, gifted teacher and speaker, a vocal advocate of public outreach, and friend to all who knew him. Oliver was born in New Rochelle, New York, during late fall 1939 on November 24. His father, James P. Oliver, was a naval officer and his mother was the former Dorothy Armstrong Cambell. Oliver's early days were spent in various cities due to his father's military life but he eventually received a high school diploma from Princess Ann High School in Virginia. Oliver subsequently graduated with a bachelor of science degree in physics in 1963 from the prestigious Rensselaer Polytechnic Institute in Troy. Lick Observatory awarded him a graduate assistantship so he moved west to California where he met and, on November 2, 1963, married Barbara Kay McKenna, who became his lifelong love and partner. In California Oliver had the good fortune to work with several eminent astronomers. This included Albert E. Whifford, director of Lick Observatory and known for his work on interstellar reddening, and Merle F. Walker, an expert in photometry, who also helped establish Pluto's rotation period. His close relation with Lawrence H. Aller, one of the 20th century's memorable astronomers, known for his ability to combine observation, theory and education, and for his care and kindness, helped bind Oliver and astronomy together for life. Oliver would also join the technical staff of the Aerospace Corporation, become an acting director of the Pine Mountain Observatory (University of Oregon), and a research assistant at the University of California in Los Angeles. Eventually, he earned both a master's degree (1968) and Ph.D. (1974) in astronomy from this well-known institution. The brilliant and eminent astronomer Daniel M. Popper supervised Oliver's doctoral dissertation, "An Investigation of Eclipsing Binary Stars Exhibiting Calcium II Emission." This research suggested that many systems Oliver investigated belonged to a new category of variable eclipsing binary stars. Popper had previously defined this new class of stars based on spectral features and intended AR Lac to be its prototype. Instead, using Oliver's suggestion, this class became known as RS CVn variables. Rare among astronomers, Popper himself was fussy about errors of measurement-uncompromising about accurate, conscientious work and intolerant about careless research. Oliver was the only student to receive a Ph.D. under this authoritative and honest astronomer, a testament to Oliver's own talents. As a University of Florida faculty member and astronomer, Oliver occupied many roles, including service as associate department chair, director of the university's Rosemary Hill Observatory near Bronson, Florida, and both undergraduate and graduate coordinators. He made significant contributions to both the operation and instrumentation of telescopes at Rosemary Hill Observatory. The establishment of the observatory's 18-inch Ritchey-Crétien telescope as a working telescope was a major accomplishment for which he wrote its operational software and programs for high speed occultation observations of stars. In addition, he was responsible for both relocating the campus teaching observatory to its present site and its operation during the 1970s. Oliver taught thousands of students both basic astronomy and advanced topics in undergraduate and graduate courses including an important sequence of graduate courses on binary stars. Faculty and students also applauded his superb, advanced course on techniques of observational astronomy. In addition, he was always looking for new techniques to improve teaching. He was among the first to adopt new technologies in the classroom, especially PowerPoint techniques for which he received university grants. Oliver's computer skills also allowed him to design several, simple but important programs to help students understand difficult subjects. A favorite, "Oliver's Orrery," clearly shows how different models of the solar system produce planetary motions, a program that remains unique. Research interests involved 3-mm radio astronomy, photometry of eclipsing binary systems, and the design of astronomical instruments and computer controlled telescopes. Oliver was the first visiting astronomer of the Copernicus Institute in Warsaw, Poland, where he helped participate in its establishment. He also held a joint appointment as Senior Research Scientist at UF's Institute for Space Science and Technology from 1988 to 1994. During this time he was a co-investigator on the Long Duration Exposure Facility/Interplanetary Dust Experiment and the Clementine Orbital Meteoroid and Debris Counter. These experiments obtained data on the impact flux of natural micrometeoroids and provided information on the population of small mass, man-made debris in near Earth space. Oliver was twice a NASA Faculty Research Fellow at the Jet Propulsion Laboratory where he developed models used to predict meteoroid impacts on space probes. He was always excited about discovering orbital debris clouds around the Earth. A favorite and special project from 1984 to 1988 was Oliver's involvement as co-investigator on UF's South Pole Optical Telescope where his knowledge of computer controlled instruments was vital. He visited the Amundsen-Scott South Pole station four times during Antarctic summers and the U.S. State Department and U.S. Navy awarded him the Antarctic Service Medal for activities in Antarctica in October 1986. This small, specialized instrument, the first stellar telescope located at Earth's South Pole, operated for several seasons evaluating observing conditions at in the visible region of the spectrum. In his last two years Oliver embarked on another unique project. In the North Irish town of Armagh, home of the Armagh Observatory, now stands a large, two-meter diameter "Celestial Sphere" made from solid polished grey granite. This impressive and beautiful star ball rests on one of four large base stones engraved to depict the story of the development of astronomy through the ages. On its surface, artist Brian Connolly has etched the brightest stars and other features of the sky in gold. The sphere is aligned north with the stars and correctly oriented toward the pole star. Although this artwork is the vision of the artist, Oliver provided the templates for the precise positions of stars and other heavenly features on the sphere. Oliver had a long interest in public programming and public schools. He actively worked with middle school science teachers, was a creator of "Conversations About Science and Mathematics" and was an innovator in large classroom teaching. He volunteered as a science- and engineering-fair judge for more than twenty years, finally stopping only about a year before his death. Members of the Alachua Astronomy Club, Inc., favorably knew him for his interesting, absorbing and clear presentations. Few could converse as well on the wide spectrum of knowledge that modern astronomy now entails. Predeceased by a son, Michael, he leaves behind his wife Barbara of forty-seven years, three children, Jennifer, Keith and Rebecca, two grandchildren, Elspeth and Moira, and a great granddaughter, Dorothy. Oliver also left behind dear friends, colleagues, students and a legacy difficult to match. He was proud of the department that he had helped shape during his long tenure at UF. Oliver was unique among many astronomers due to his abilities and flair as an excellent speaker and teacher, a superb instrumentalist and programmer, and as a talented research scientist with an unequaled passion and dedication to astronomy and his department.

Modelling of the impact of the Rhone River N:P ratios over the NW Mediterranean planktonic food web

NASA Astrophysics Data System (ADS)

Alekseenko, Elena; Baklouti, Melika; Carlotti, François

2016-04-01

The origin of the high N:P ratios in the Mediterranean Sea is one of the remaining important questions raised by the scientific community. During the last two decades it was observed that the inorganic ratio NO3:PO4 ratio in major Mediterranean rivers including the Rhone River has dramatically increased, thereby strengthening the P-limitation in the Mediterranean waters (Ludwig et al, 2009, The MerMex group, 2011) and, as a result, increasing the anomaly in the ratio NO3:PO4 of the Gulf of Lions (GoL) and in all the western part of NW Mediterranean. The N:P ratios in seawater and in the metabolic requirements for plankton growth are indeed of particular interest, as these proportions determine which nutrient will limit biological productivity at the base of the food web and may select plankton communities with distinct biogeochemical function (Deutsch &Weber, 2012). In this context, an in the same spirit as the study of Parsons & Lalli (2002), an interesting question is whether high NO3:PO4 ratios in sea water can favor dead-end gelatinous food chains to the detriment of chains producing fish or direct food for fish . More generally, we aim at characterizing the impact of changes in the NO3:PO4 ratio on the structure of the planktonic food web in the Mediterranean Sea. Coupled physical-biogeochemical modeling with the Eco3M-MED biogeochemical model (Baklouti et al., 2006a,b, Alekseenko et al., 2014) coupled with the hydrodynamic model MARS3D (Lazure&Dumas, 2008) is used to investigate the impact of Rhone River inputs on the structure of the first levels of the trophic web of the NW Mediterranean Sea. The fact that the model describes each biogenic compartment in terms of its abundance (for organisms), and carbon, phosphorus, nitrogen and chlorophyll (for autotrophs) contents means that the intracellular quotas and ratios of each organism can be calculated at any time. This provides information on the intracellular status of organisms, on the elements that limit their growth and ultimately enhances our understanding of the functioning of this planktonic food-web. The present work consisted in running two different scenarios (low and high NO3:PO4 in the Rhone River). The lower ratio is the one presently found in the Rhône river outputs while the higher ratio is twice the lower one.The study focused on a one-year period (2010) since the model outputs during this period have already been partially validated (Alekseenko et al., 2014). At this stage, we first explore the spatial and temporal dynamics of the carbon stocks, in living and non-living compartments as well as related carbon fluxes. Results showed that, after one year of simulation, the change in NO3:PO4 of Rhone River mostly impacts organisms in the shelf zone of GoL, and especially the lowest trophic levels during the spring phytoplankton bloom. The increase in NO3:PO4 decreases primary production and bacterial production rates, thereby decreasing food availability for zooplankton which population growth decreases. During the spring phytoplankton bloom period, the decrease in Chl-a induced by the high NO3:PO4 Rhone ratio has an order of value comparable to the Chl-a mean level observed in the GoL. In the case of the scenario with high NO3:PO4 ratio, bacterial production increases after the spring bloom, what, in turn, increases the development of ciliates. The impact of NO3:PO4 scenarios on the mesozooplankton and jellyfish compartments considered in the model is overall low after a one-year simulation, but, probably due to their longer life cycle comparing to smaller organisms, this should be investigated at longer time scales. Acknowledgements The present research is a contribution to the Labex OT-Med (n_ ANR-11-LABX-0061) funded by the French Government «Investissements d'Avenir» program of the French National Research Agency (ANR) through the A*MIDEX project (n_ ANR-11 IDEX-0001-02). The work is also partially supported by the grant of Russian Foundation for Basic Research (RFBR) n°16-35-00526. References 1. Alekseenko E., Raybaud V., Espinasse B., Carlotti F., Queguiner B., Thouvenin B., Garreau P., Baklouti M. (2014) Seasonal dynamics and stoichiometry of the planktonic community in the NW Mediterranean Sea: a 3D modeling approach. Ocean Dynamics IN PRESS. http://dx.doi.org/10.1007/s10236-013-0669-2 2. Baklouti M, Diaz F, Pinazo C, Faure V, Quequiner B (2006a) Investigation of mechanistic formulations depicting phytoplankton dynamics for models of marine pelagic ecosystems and description of a new model. Prog Oceanogr 71:1-33 3. Baklouti M, Faure V, Pawlowski L, Sciandra A (2006b) Investigation and sensitivity analysis of a mechanistic phytoplankton model implemented in a new modular tool (Eco3M) dedicated to biogeochemical modelling. Prog Oceanogr 71:34-58 4. Deutsch, C. and Weber, T. (2012) Nutrient ratios as a tracer and driver of ocean biogeochemistry. Annual Review of Marine Science, 4:113-141 5. Krom MD, Herut B, Mantoura RFC (2000) Nutrient budget for the Eastern Mediterranean: implications for phosphorus limitation. Limnol Oceanogr 49(5):1582-1592 6. Lazure P, Dumas F (2008) An external-internal mode coupling for a 3D hydrodynamical model for applications at regional scale (MARS). Adv Water Resour 31(2):233-250 7. Ludwig, W., Dumont, E., Meybeck, M., Heussner, S. (2009). River discharges of water and nutrients to the Mediterranean and Black Sea: Major drivers for ecosystem changes during past and future decades? Progress in Oceanography 80, pp. 199-217 8. Parsons, T. R., and Lalli, C. M. (2002) Jellyfish population explosions: Revisiting a hypothesis of possible causes. La Mer 40: 111-121. 9. The MerMex Group, Durrieu de Madron X, Guieu C, Sempéré R, Conan P, Cossa D, D'Ortenzio F, Estournel C, Gazeau F, Rabouille C, Stemmann L, Bonnet S, Diaz F, Koubbi P, Radakovitch O, Babin M, Baklouti M, Bancon-Montigny C, Belviso S, Bensoussan N, Bonsang B, Bouloubassi I, Brunet C, Cadiou J-F, Carlotti F, Chami M, Charmasson S, Charrière B, Dachs J, Doxaran D, Dutay J-C, Elbaz-Poulichet F, Eléaume M, Eyrolles F, Fernandez C, Fowler S, Francour P, Gaertner JC, Galzin R, Gasparini S, Ghiglione J-F, Gonzalez J-L, Goyet C, Guidi L, Guizien K, Heimbürger L-E, Jacquet SHM, Jeffrey WH, Joux F, Le Hir P, Leblanc K, Lefèvre D, Lejeusne C, Lemé R, Loÿe-Pilot M-D, Mallet M, Méjanelle L,Mélin F, Mellon C, Mérigot B, Merle P-L, Migon C, Miller WL, Mortier L, Mostajir B, Mousseau L, Moutin T, Para J, Pérez T, Petrenko A, Poggiale J-C, Prieur L, Pujo-Pay M, Pulido-Villena, Raimbult P, Rees AP, Ridame C, Rontani J-F, Ruiz Pino D, Sicre MA, Taillandier V, Tamburini C, Tanaka T, Taupier-Letage I, Tedetti M, Testor P, Thébault H, Thouvenin B, Touratier F, Tronczynski J, Ulses C, Van Wambeke F, Vantrepotte V, Vaz S, Verney R (2011) Marine ecosystems' responses to climatic and anthropogenic forcings in the Mediterranean. Prog Oceanogr 91:97-166

Obituary: Thomas Gold, 1920-2004

NASA Astrophysics Data System (ADS)

Dermott, Stanley F.

2004-12-01

Thomas "Tommy" Gold died of heart disease at Cayuga Medical Center, Ithaca NY on 22 June 2004 at the age of 84. He will be remembered as one of the most interesting, dynamic and influential scientists of his generation. Tommy's paradigm-changing ideas in astronomy and planetary science, while original and bold, were also highly controversial. With his radical work on the origin of natural gas and petroleum, the controversy is likely to continue. Tommy was born in Vienna, Austria on 22 May 1920, moving with his family to Berlin at age 10 and then, after the rise of Hitler in 1933, to England. His parents were Josephine (nee Martin) and Maximillian Gold, a successful steel magnate. Tommy was educated at Zuoz College in Switzerland where he became an expert skier and developed an athletic prowess that he maintained throughout his life, winning a NASTAR gold medal for skiing at the age of 65. He studied Mechanical Sciences at Trinity College, Cambridge, but much to his disgust his education was interrupted because of internment by the British as a suspected enemy alien. That unfortunate period (I remember him saying to me "Can you believe the stupidity, interring people like me who had fled from Nazi Germany?") had one good outcome: on his first night in camp he met Hermann Bondi who had an important influence on his early development as a scientist. They were both born in Vienna, their parents knew each other, and they were fellow students at Trinity, but this was their first meeting. On release, he went immediately into top-secret radar research for the British Admiralty, working as a team with Bondi and Fred Hoyle in a farm cottage in Dunsfold, Surrey. Tommy's first published research, which was a Nature paper with R.J. Pumphrey in 1947, was not in astronomy but physiology. He applied his engineer's understanding of positive feedback to develop and test a resonance model for how the human ear determines pitch. His conclusion that pitch discrimination occurs physically in the inner ear and not in the brain was largely ignored at the time, but has since been proved correct. At about the same time, he started work with Bondi and Hoyle on the steady state theory of the universe. This attractive hypothesis, which was proposed by Tommy, supposes that the universe is infinite in both time and space, but to reconcile this with Hubble's observations of receding galaxies, matter needs to be created continuously. This struck the trio as no more shocking than creating all of the matter all at once. Tommy stated that "in choosing a hypothesis there is no virtue in being timid." The steady state theory stimulated one of the greatest cosmological debates of the twentieth century. The initial opposition to the theory, led by Martin Ryle, was based on number counts of radio sources. Current observations, particularly of the thermal cosmic background radiation, support the rival theory that Hoyle derisively named the Big Bang. The rivalry stimulated much observational radio astronomy and theoretical work on the origin of elements; one positive outcome for Tommy was that he argued that some of the radio sources observed by Ryle must be external to our galaxy and in that, he was certainly correct. Some of the other problems that engaged Tommy can also be traced back to early conversations with Bondi and Hoyle. In 1955, Hoyle outlined "Gold's pore theory" and the abiogenic origin of hydrocarbons in his book Frontiers of Astronomy, contrasting those ideas with the "curious theory that oil is derived from dead fish." In later years, Tommy was to expand on those ideas, linking the origin of all hydrocarbons to primordial processes that survived the formation of the Earth and Moon. The observation that all petroleum contains clear signatures of biological activity led him to propose that the Earth has a "deep hot biosphere" and it is the action of microbes feeding on methane seeping up from deep in the mantle that gives petroleum the imprint of life. Tommy made novel and ingenious contributions to many other areas of astronomy, ranging from electromagnetic and dynamical processes in the solar system, to the origin of solar flares, cosmic rays and pulsars. At a time when celestial mechanics was largely concerned with determining the positions and masses of planets and satellites, Tommy suggested to his student Peter Goldreich that the observed excess of orbital resonances amongst the satellites might involve tidal evolution. Goldreich's work on this fruitful topic was later extended by Stanton Peale, another of Tommy's former students, to account for the spectacular melting of Io by tidal dissipation. His work on lunar dust was controversial partly because in lectures and popular articles he raised the possibility, using the analogy of snow-covered glacial crevasses, that deep layers of dust could pose a threat to astronauts. However, his suggestion that the Moon is covered in a layer of dust was essentially confirmed by the Apollo lunar landings. But, while he was right to suggest that the color of the Moon is determined by the space weathering of this dust, he was wrong to argue that the lunar maria are not lava. Shortly after the discovery of pulsars, Tommy suggested that they are rapidly rotating, magnetized, neutron stars whose magnetospheres (a word that he coined) reached the light cylinder beyond which particles could not rotate. This initially controversial idea (he was not allowed to present it at one meeting) was widely accepted after the discovery of the pulsar in the Crab nebula. Tommy showed that particles electromagnetically accelerated by a neutron star could generate cosmic rays, and he linked the resultant power loss with the observed braking of the pulsar's spin. His unusual talents received early recognition and garnered him many honors. For his brilliant work on human hearing he was awarded a Fellowship at Trinity College. After switching to astronomy, he was appointed Chief Assistant to the Astronomer Royal in 1956, but soon left England for greater opportunities in the United States. He spent two years (1957-58) at Harvard, first as a professor and then as the Robert Wheeler Willson Professor of Applied Astronomy before accepting positions as chairman of astronomy and Director of the Center for Radiophysics and Space Research at Cornell University in 1959. He took great pride in the astronomy department that blossomed into greatness under his leadership. The department, which only had one other faculty member when he was appointed, reflected Tommy's strengths, ranging from radio astronomy and the Arecibo dish, to infrared, theoretical and planetary astronomy. His many distinguished hires included Carl Sagan. At Cornell, he was Assistant Vice President for Research from 1969-71 and the John L.Wetherill Professor from 1971 until his retirement in 1987. His many honors included Fellow of the Royal Society (London); Member of the National Academy of Sciences (US); Gold Medal and George Darwin Lecture, Royal Astronomical Society, London; and Honorary Doctor of Science, Cambridge University. He also served on the US President's Science Advisory Committee, although he came to be a strong critic of NASA and the Shuttle program. Tommy was a handsome, charming and generous man and a loyal colleague who formed many long-lasting friendships. A witty and articulate speaker, he was regarded by some as a scientific maverick who delighted in controversy. In reality, he was an iconoclast whose strength was in penetrating analysis of the assumptions on which some of our most important theories are based. He is survived by his second wife, Carvel (nee Beyer) Gold of Ithaca whom he married in 1972, and by the couple's daughter, Lauren Gold of West Palm Beach, Florida, as well as by three daughters from his first marriage to Merle Eleanor Tuberg in 1947: Lindy Bryant of Philadelphia, Lucy Gold of Ithaca and Tanya Vanesse of Carmel, N.Y., and by six grandchildren. He was predeceased by a sister, Elisabeth Carter. Photo credit: Photograph by Herman J. Eckelmann, Ithaca, New York

Obituary: John W. Firor (1927-2007)

NASA Astrophysics Data System (ADS)

Gilman, Peter A.

2009-12-01

John W. Firor, a former Director of the High Altitude Observatory and the National Center for Atmospheric Research, and a founder of the Solar Physics Division of the American Astronomical Society, died of Alzheimer's disease in Pullman, Washington on November 5, 2007, he was 80. He was born in Athens Georgia on October 18, 1927, where his father was a professor of agricultural economics. John had an unusually diverse scientific career. His interest in physics and astrophysics began while serving in the army, during which time he was assigned to the Los Alamos National Laboratory, where he guarded highly radioactive materials (many have heard him describe how informal the protections were compared to later times). After his service he returned to college and graduated in physics from Georgia Tech in 1949. He received his Ph.D. from the University of Chicago in 1954, writing his thesis on cosmic rays under John Simpson. John Firor would later remark that: "If you needed cosmic rays to actually do anything, you are sunk." That thought, partly in jest, may help explain his motivation for moving to so many new scientific and management pursuits. John moved from cosmic ray physics to radio astronomy (particularly of the Sun) when he began work at the Carnegie Institution of Washington's Department of Terrestrial Magnetism, where he remained until 1961. During this time, he met Walter Orr Roberts, then the Director of the High Altitude Observatory (HAO) in Boulder, Colorado. HAO was then affiliated with the University of Colorado. In 1959, a movement began to upgrade the atmospheric sciences in the United States by establishing a National Center, where the largest, most important atmospheric research problems could be addressed. Roberts became the first Director of NCAR, as well as the first president of the University Corporation for Atmospheric Research (UCAR), the consortium of universities that was commissioned to manage and staff the new Center. HAO became a scientific division of NCAR (Roberts made it a requirement if he was to be NCAR Director). He chose John to be the new HAO Director. John was 33 then; his leadership potential was recognized very early. While Director of HAO, John presided over a very active scientific program that focused on non-equilibrium thermodynamics, radiative transfer, plasma physics, coronal spectroscopy, geomagnetism, physics of the Earth's upper atmosphere, and solar activity. Prominent scientists such as Jack Evans, Sydney Chapman, Gene Parker, Leo Goldberg and Donald Menzel visited to share their insights and enthusiasm with the HAO staff. John was also an active participant in HAO's well-known solar eclipse expeditions, traveling to New Guinea and to Lake Chad in Africa. Late in his tenure as HAO Director, he took the lead in helping to improve the involvement of the AAS in solar physics, and solar physicists in the AAS. Having led the AAS committee that planned its birth, he was the founding chair of the new Solar Physics Division. Much less importantly, he gave me a summer position in 1966 when I was joining the faculty at CU--that is when I first met John. In 1968, John became the Director of NCAR when Walter Roberts decided to split the directorship from the Presidency of UCAR. As NCAR Director, John had responsibility for a vastly broadened program compared to his HAO days. NCAR, the largest NSF supported research center, conducted research covering all of atmospheric sciences, as well as oceanography and solar-terrestrial physics. It also provided major observational and computational facilities to the atmospheric sciences community. John showed very quickly he understood and could guide all of it. I came to know John best during this period, because in 1971 he chose me to head the Advanced Study Program, which supported (and still supports) postdoctoral and graduate education. In that time, budgets were good, and NCAR was a relatively collegial, informal place. But in December 1973, that all changed suddenly. NCAR management was reviewed by an NSF-appointed Joint Evaluation Committee (JEC), whose report raised many questions. Walter Roberts resigned as UCAR President, and John had the task of working with the UCAR Board to make major changes. During this time, John asked me to put aside my ASP duties to assist him. Over the next 18 months, NCAR was restructured, several Division Directors replaced, a new, more rigorous scientific appointment system was developed, and a major budget cut was absorbed. John did all of this; in my view, it was heroic. Then the UCAR Board appointed a new UCAR President and NCAR Director, Francis Bretherton, and John became the NCAR Executive Director. John used to say that many people asked him how he felt about being 'demoted'--always gracious, he said he never saw it that way. In fact, he was mentoring Bretherton, who was very junior to John in experience, never having held a major management position. The Bretherton-Firor 'team' managed UCAR until 1980. Then a new UCAR and NCAR management was chosen, and John had to decide what to do next. He took a sabbatical and became more deeply involved in environmental issues. But this interest had been kindled much before. As early as 1970, he was writing and speaking about environmental questions while NCAR Director. When he returned to NCAR, he became the Director of the Advanced Study Program (ASP), what I had been a decade before. He served NCAR in that role until 1996. When he stepped down, he remarked that he had been a member of the NCAR Directors Committee for 34 years; a record that he judged should never be broken. While John was attentive to the needs of the post-docs and graduate students his program supported, ASP was a platform for him to pursue his environmental interests. He spoke and wrote clearly and influentially on environmental issues. He served on the Boards of several important environmental organizations and wrote two well received environmental books: "The Changing Atmosphere: A Global Challenge" (1990), and, with his wife Judith Jacobsen "The Crowded Greenhouse: Population, Climate Change and Creating a Sustainable World" (2002). After ASP, he continued his focus on environmental issues as a member of the Environmental and Societal Impacts group at NCAR. John retired from NCAR in 2005. John had many active pursuits beyond his professional work. He was an accomplished pilot, with licenses for flying single and multiengine aircraft, sailplanes, and balloons. He piloted a sailplane in at least one meteorological field program. He also was an avid river rafter. John faced the disease that took his life as he did all events in his life, with grace and dignity. He endured the loss of two spouses to cancer, Merle Jenkins Firor in 1979, and Judith Jacobsen in 2004. John is survived by his four children with his first wife, Daniel Firor of Seattle, Washington; Kay Firor of Cove, Oregon; James Firor of Hotchkiss, Colorado, and Susan Firor of Moscow, Idaho; a sister; a brother; and three grandchildren. His children and his many friends in Boulder and elsewhere gave him loving support during his days battling Alzheimer's. John used to define a 'southern gentleman' as a man dressed in white linen suit on a hot dusty summer day in a small Georgia town who could cross the street without breaking a sweat. John and his intellect and his management ability were like that; he could deal gracefully and successfully with almost anything that came his way. A man of great accomplishment, he rarely showed an ego to match. In the darkest days following the JEC Report, he almost single-handedly invented a new NCAR scientific appointment system. He chose the first cadre of 'senior scientists' to populate the top rank. There were about eighteen members in this group, but there was one name conspicuously absent - his own. This 'error' was quietly corrected by the UCAR Board.