A β-solenoid model of the Pmel17 repeat domain: insights to the formation of functional amyloid fibrils

Science.gov (United States)

Louros, Nikolaos N.; Baltoumas, Fotis A.; Hamodrakas, Stavros J.; Iconomidou, Vassiliki A.

2016-02-01

Pmel17 is a multidomain protein involved in biosynthesis of melanin. This process is facilitated by the formation of Pmel17 amyloid fibrils that serve as a scaffold, important for pigment deposition in melanosomes. A specific luminal domain of human Pmel17, containing 10 tandem imperfect repeats, designated as repeat domain (RPT), forms amyloid fibrils in a pH-controlled mechanism in vitro and has been proposed to be essential for the formation of the fibrillar matrix. Currently, no three-dimensional structure has been resolved for the RPT domain of Pmel17. Here, we examine the structure of the RPT domain by performing sequence threading. The resulting model was subjected to energy minimization and validated through extensive molecular dynamics simulations. Structural analysis indicated that the RPT model exhibits several distinct properties of β-solenoid structures, which have been proposed to be polymerizing components of amyloid fibrils. The derived model is stabilized by an extensive network of hydrogen bonds generated by stacking of highly conserved polar residues of the RPT domain. Furthermore, the key role of invariant glutamate residues is proposed, supporting a pH-dependent mechanism for RPT domain assembly. Conclusively, our work attempts to provide structural insights into the RPT domain structure and to elucidate its contribution to Pmel17 amyloid fibril formation.

Contribution of the LIM domain and nebulin-repeats to the interaction of Lasp-2 with actin filaments and focal adhesions.

Directory of Open Access Journals (Sweden)

Hiroyuki Nakagawa

Full Text Available Lasp-2 binds to actin filaments and concentrates in the actin bundles of filopodia and lamellipodia in neural cells and focal adhesions in fibroblastic cells. Lasp-2 has three structural regions: a LIM domain, a nebulin-repeat region, and an SH3 domain; however, the region(s responsible for its interactions with actin filaments and focal adhesions are still unclear. In this study, we revealed that the N-terminal fragment from the LIM domain to the first nebulin-repeat module (LIM-n1 retained actin-binding activity and showed a similar subcellular localization to full-length lasp-2 in neural cells. The LIM domain fragment did not interact with actin filaments or localize to actin filament bundles. In contrast, LIM-n1 showed a clear subcellular localization to filopodial actin bundles. Although truncation of the LIM domain caused the loss of F-actin binding activity and the accumulation of filopodial actin bundles, these truncated fragments localized to focal adhesions. These results suggest that lasp-2 interactions with actin filaments are mediated through the cooperation of the LIM domain and the first nebulin-repeat module in vitro and in vivo. Actin filament binding activity may be a major contributor to the subcellular localization of lasp-2 to filopodia but is not crucial for lasp-2 recruitment to focal adhesions.

ST proteins, a new family of plant tandem repeat proteins with a DUF2775 domain mainly found in Fabaceae and Asteraceae.

Science.gov (United States)

Albornos, Lucía; Martín, Ignacio; Iglesias, Rebeca; Jiménez, Teresa; Labrador, Emilia; Dopico, Berta

2012-11-07

Many proteins with tandem repeats in their sequence have been described and classified according to the length of the repeats: I) Repeats of short oligopeptides (from 2 to 20 amino acids), including structural cell wall proteins and arabinogalactan proteins. II) Repeats that range in length from 20 to 40 residues, including proteins with a well-established three-dimensional structure often involved in mediating protein-protein interactions. (III) Longer repeats in the order of 100 amino acids that constitute structurally and functionally independent units. Here we analyse ShooT specific (ST) proteins, a family of proteins with tandem repeats of unknown function that were first found in Leguminosae, and their possible similarities to other proteins with tandem repeats. ST protein sequences were only found in dicotyledonous plants, limited to several plant families, mainly the Fabaceae and the Asteraceae. ST mRNAs accumulate mainly in the roots and under biotic interactions. Most ST proteins have one or several Domain(s) of Unknown Function 2775 (DUF2775). All deduced ST proteins have a signal peptide, indicating that these proteins enter the secretory pathway, and the mature proteins have tandem repeat oligopeptides that share a hexapeptide (E/D)FEPRP followed by 4 partially conserved amino acids, which could determine a putative N-glycosylation signal, and a fully conserved tyrosine. In a phylogenetic tree, the sequences clade according to taxonomic group. A possible involvement in symbiosis and abiotic stress as well as in plant cell elongation is suggested, although different STs could play different roles in plant development. We describe a new family of proteins called ST whose presence is limited to the plant kingdom, specifically to a few families of dicotyledonous plants. They present 20 to 40 amino acid tandem repeat sequences with different characteristics (signal peptide, DUF2775 domain, conservative repeat regions) from the described group of 20 to 40

HR Connect

Data.gov (United States)

US Agency for International Development — HR Connect is the USAID HR personnel system which allows HR professionals to process HR actions related to employee's personal and position information. This system...

Molecular dynamics of Middle East Respiratory Syndrome Coronavirus (MERS CoV) fusion heptad repeat trimers

KAUST Repository

Kandeel, Mahmoud

2018-05-17

Structural studies related to Middle East Respiratory Syndrome Coronavirus (MERS CoV) infection process are so limited. In this study, molecular dynamics (MD) simulation was carried out to unravel changes in the MERS CoV heptad repeat domains (HRs) and factors affecting fusion state HR stability. Results indicated that HR trimer is more rapidly stabilized, having stable system energy and lowest root mean square deviations (RMSDs). While trimers were the predominant active form of CoVs HR, monomers were also discovered in both of viral and cellular membranes. In order to find the differences between S2 monomer and trimer molecular dynamics, S2 monomer were modelled and subjected to MD simulation. In contrast to S2 trimer, S2 monomer was unstable, having high RMSDs with major drifts above 8 Å. Fluctuation of HR residue positions revealed major changes in the C-terminal of HR2 and the linker coil between HR1 and HR2 in both monomer and trimer. Hydrophobic residues at the “a” and “d” positions of HR helices stabilize the whole system, having minimal changes in RMSD. The global distance test and contact area difference scores support instability of MERS CoV S2 monomer. Analysis of HR1-HR2 inter-residue contacts and interaction energy revealed three different energy scales along HR helices. Two strong interaction energies were identified at the start of the HR2 helix and at the C-terminal of HR2. The identified critical residues by MD simulation and residues at a and d position of HR helix were strong stabilizers of HRs recognition.

HPV test by Hybrid Capture II for the diagnosis of HR-HPV persistent infection.

Science.gov (United States)

Serour, Y; Bendahmane, M; Abbou Baker, F; Medles, M; Moueddene, B; Kraiba, R

2017-11-01

Persistent high-risk HPV (HR-HPV) infection is associated with a greater risk of cervical cancer. Statistical data on the prevalence of HR-HPV infections in the Algerian population is lacking. We conducted a prospective study of 300 women aged between 25 and 50 years, screened for cervical cancer from 2012 to 2015 in Sidi Bel Abbès, a western region of Algeria. We aimed to assess the reliability of the repeated use of the HC II test (three longitudinal HPV tests 9 months apart from each other) in diagnosing the persistence of HR-HPV infection. The prevalence of HR-HPV infection was 7.33% and infected women were aged 37.9±3years. For 90.9% of HR-HPV-positive patients, the infection persisted for a mean of 18.5months [95% CI: 16.9-22.1months]. Among these patients, 55.55% developed CIN1 and 11.11% developed CIN2. The sensitivity of the HC II test was 81.74% [95% CI: 71.3-89.6] and its positive predictive value associated with abnormal cervical biopsy was 27.49% [95% CI: 16.0-33.33]. Repeating the HC II test is a good predictor for identifying women at high risk of cervical cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Tetratricopeptide repeat domain 9A is an interacting protein for tropomyosin Tm5NM-1

International Nuclear Information System (INIS)

Cao, Shenglan; Ho, Gay Hui; Lin, Valerie CL

2008-01-01

Tetratricopeptide repeat domain 9A (TTC9A) protein is a recently identified protein which contains three tetratricopeptide repeats (TPRs) on its C-terminus. In our previous studies, we have shown that TTC9A was a hormonally-regulated gene in breast cancer cells. In this study, we found that TTC9A was over-expressed in breast cancer tissues compared with the adjacent controls (P < 0.00001), suggesting it might be involved in the breast cancer development process. The aim of the current study was to further elucidate the function of TTC9A. Breast samples from 25 patients including the malignant breast tissues and the adjacent normal tissues were processed for Southern blot analysis. Yeast-two-hybrid assay, GST pull-down assay and co-immunoprecipitation were used to identify and verify the interaction between TTC9A and other proteins. Tropomyosin Tm5NM-1 was identified as one of the TTC9A partner proteins. The interaction between TTC9A and Tm5NM-1 was further confirmed by GST pull-down assay and co-immunoprecipitation in mammalian cells. TTC9A domains required for the interaction were also characterized in this study. The results suggested that the first TPR domain and the linker fragment between the first two TPR domains of TTC9A were important for the interaction with Tm5NM-1 and the second and the third TPR might play an inhibitory role. Since the primary function of tropomyosin is to stabilize actin filament, its interaction with TTC9A may play a role in cell shape and motility. In our previous results, we have found that progesterone-induced TTC9A expression was associated with increased cell motility and cell spreading. We speculate that TTC9A acts as a chaperone protein to facilitate the function of tropomyosins in stabilizing microfilament and it may play a role in cancer cell invasion and metastasis

Recombinant protein of heptad-repeat HR212, a stable fusion inhibitor with potent anti-HIV action in vitro

International Nuclear Information System (INIS)

Pang, Wei; Wang Ruirui; Yang Liumeng; Liu Changmei; Tien Po; Zheng Yongtang

2008-01-01

HR212, a recombinant protein expressed in Escherichia coli, has been previously reported to inhibit HIV-1 membrane fusion at low nanomolar level. Here we report that HR212 is effective in blocking laboratory strain HIV-1 IIIB entry and replication with EC 50 values of 3.92 ± 0.62 and 6.59 ± 1.74 nM, respectively, and inhibiting infection by clinic isolate HIV-1 KM018 with EC 50 values of 44.44 ± 10.20 nM, as well as suppressing HIV-1-induced cytopathic effect with an EC 50 value of 3.04 ± 1.20 nM. It also inhibited HIV-2 ROD and HIV-2 CBL-20 entry and replication in the μM range. Notably, HR212 was highly effective against T20-resistant strains with EC 50 values ranging from 5.09 to 7.75 nM. Unlike T20, HR212 showed stability sufficient to inhibit syncytia formation in a time-of-addition assay, and was insensitive to proteinase K digestion. These results suggest that HR212 has great potential to be further developed as novel HIV-1 fusion inhibitor for treatment of HIV/AIDS patients, particularly for those infected by T20-resistant variants

The leucine-rich repeat structure.

Science.gov (United States)

Bella, J; Hindle, K L; McEwan, P A; Lovell, S C

2008-08-01

The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures.

Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG Nup Repeat Specificity

DEFF Research Database (Denmark)

Vognsen, Tina Reinholdt; Möller, Ingvar Rúnar; Kristensen, Ole

2013-01-01

Ras GTPase Activating Protein SH3 Domain Binding Protein (G3BP) is a potential anti-cancer drug target implicated in several cellular functions. We have used protein crystallography to solve crystal structures of the human G3BP1 NTF2-like domain both alone and in complex with an FxFG Nup repeat...... peptide. Despite high structural similarity, the FxFG binding site is located between two alpha helices in the G3BP1 NTF2-like domain and not at the dimer interface as observed for nuclear transport factor 2. ITC studies showed specificity towards the FxFG motif but not FG and GLFG motifs. The unliganded...

Study of domain depinning during repeated polarization reversal in hard PZT ceramics using acoustic emission

International Nuclear Information System (INIS)

Prabakar, K; Rao, S P Mallikarjun

2006-01-01

Acoustic emission (AE) has been studied during repeated polarization reversals (at 50 Hz) in hard PZT-8 ceramics. The AE and hysteresis loop were monitored at regular intervals of electric field (±20 kV cm -1 peak) application till 10 8 cycles. The sample did not fatigue and an increase in saturation polarization (Ps) was observed. AE was observed with zero threshold till 10 5 cycles when the field was increasing in both half cycles of the applied field. The initial increase in AE activity with increasing number of field cycles till 10 5 was explained on the basis of defect dipoles encouraging the 90 deg. domain switches, i.e. domain depinning. The decrease in AE activity, an increase in threshold field for the observed AE and a further increase in Ps after 10 5 cycles were explained based on the changes in the orientation of defect dipoles with respect to Ps due to the applied field cycles. This was found to encourage the 180 0 domain switches but pin the 90 deg. domains. An increase in AE at 10 8 cycles after applying a higher field of ±25 kV cm -1 was found to be mainly due to microcracking

Entry into the nuclear pore complex is controlled by a cytoplasmic exclusion zone containing dynamic GLFG-repeat nucleoporin domains.

Science.gov (United States)

Fiserova, Jindriska; Spink, Matthew; Richards, Shane A; Saunter, Christopher; Goldberg, Martin W

2014-01-01

Nuclear pore complexes (NPCs) mediate nucleocytoplasmic movement. The central channel contains proteins with phenylalanine-glycine (FG) repeats, or variations (GLFG, glycine-leucine-phenylalanine-glycine). These are 'intrinsically disordered' and often represent weak interaction sites that become ordered upon interaction. We investigated this possibility during nuclear transport. Using electron microscopy of S. cerevisiae, we show that NPC cytoplasmic filaments form a dome-shaped structure enclosing GLFG domains. GLFG domains extend out of this structure and are part of an 'exclusion zone' that might act as a partial barrier to entry of transport-inert proteins. The anchor domain of a GLFG nucleoporin locates exclusively to the central channel. By contrast, the localisation of the GLFG domains varied between NPCs and could be cytoplasmic, central or nucleoplasmic and could stretch up to 80 nm. These results suggest a dynamic exchange between ordered and disordered states. In contrast to diffusion through the NPC, transport cargoes passed through the exclusion zone and accumulated near the central plane. We also show that movement of cargo through the NPC is accompanied by relocation of GLFG domains, suggesting that binding, restructuring and movement of these domains could be part of the translocation mechanism.

HR Explorer

CERN Document Server

Möller, M

1997-01-01

At the European Laboratory for Particle Physics Research (CERN), Geneva Switzerland we are using OracleHR for managing our human resources since 1995. After the first year of production it became clear that there was a strong need for an easy-to-use Decision Support Tool exploring the data in OracleHR. This paper illustrates an approach which we have adopted to provide on-line management reporting, multi-dimensional analysis, drill-down and slicing & dicing of data, warehoused from OracleHR. The tool offers strong resource management and planning capabilities including career follow-up. The user management and security monitoring are implemented using the Oracle WebServer.

Triage of HR-HPV positive women with minor cytological abnormalities: a comparison of mRNA testing, HPV DNA testing, and repeat cytology using a 4-year follow-up of a population-based study.

Science.gov (United States)

Persson, Maria; Elfström, K Miriam; Brismar Wendel, Sophia; Weiderpass, Elisabete; Andersson, Sonia

2014-01-01

Expression of the viral E6/E7 oncogenes of high-risk human papillomaviruses (HR-HPV) is necessary for malignant conversion and maintenance in cervical tissue. In order to determine whether HR-HPV E6/E7 mRNA testing more effectively predicts precancerous lesions and invasive cervical cancer than HR-HPV DNA testing, we aimed to compare triage using HR-HPV E6/E7 mRNA testing by APTIMA HPV Assay (APTIMA) to HPV16 DNA testing, HPV16/18 DNA testing, and repeat cytology. Liquid-based (PreservCyt) cell samples were obtained from HR-HPV-positive women diagnosed with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) within the framework of the population-based cervical cancer screening program in Stockholm, Sweden. Samples were tested for HR-HPV E6/E7 mRNA by APTIMA (Gene-Probe Inc., San Diego, CA, USA). Women were followed up for 4 years after the index cytology via medical and laboratory records, and the Stockholm Oncology Center. Nine of 25 (36%) women in the ASCUS group, and 64 of 180 (36%) women in the LSIL group developed cervical intraepithelial neoplasia (CIN) grade 2 or worse during 4 years of follow-up. 162 (74%) women were APTIMA-positive, and APTIMA had the highest sensitivity to predict CIN2 or worse and CIN3 or worse in the ASCUS (77.8% and 100%) and LSIL (78.1 and 75.8%) groups, although specificity was insufficient (cytology were more specific than APTIMA. The results of this population-based study with comprehensive follow-up support the use of APTIMA as a triage test for women with ASCUS. More focused investigation is required for women with LSIL.

The perspective of Malaysian Manufacturing Organizations on Strategy, HR Outsourcing and HR Costs

Directory of Open Access Journals (Sweden)

Hasliza Abdul HALIM

2011-06-01

Full Text Available The paper discusses the relationship between different types of human resource management (HRM strategy and the human resource outsourcing, and impact on the size of human resource (HR department. Three HRM strategies are considered: Facilitation, accumulation and utilization. The data for the study were obtained from survey responses from 232 organizations, of which 113 were engaged in HR outsourcing. The findings suggest that organizations tend to rely on outsourcing of HR functions when they espouse facilitation and utilization HRM strategy. Concurrently, by relying on HR outsourcing, the organizations manage to experience a reduction in the size of HR department. The results show that it is important for the organizations to better understand the implications of an increased reliance on outsourcing within HR. This allows them to focus on how HR functions are delivered within organizations with the interaction of HRM strategy and the size of HR department will tend to be smaller resulting from outsourcing activities.

HR boiler

Energy Technology Data Exchange (ETDEWEB)

1982-08-01

A number of manufacturers of central heating boilers in the Netherlands have produced high-efficiency boilers, all carrying the GIVEG-HR seal of approval (GIVEG is the manufacturers' association in the Netherlands, and HR stands for 'hoog rendement': high efficiency). Efficiences were considerably improved by reducing flue, idling and radiation losses. Control and safety, discharges of flue gases and condensate need special attention. Whether installation of a GIVEG-HR boiler is profitable in view of the cost/profit ratio, will have to be determined from case to case. N.V. Nederlandse Gasunie felt it was time to present the facts so far in a way specially aimed at the construction industry. This special edition of 'Gas and Architecture' answers a number of questions which the architect or consultant engineer might have in particular before advising on the installation of the new boiler in houses and other buildings in the interests of energy saving. A technical description of the HR boiler covers the backgrounds of its development and considers the role of the Netherlands government as regards to the introduction of the boiler.

Caretakers or HR Managers

Directory of Open Access Journals (Sweden)

James Baba Abugre

2014-08-01

Full Text Available Do human resources (HR managers in developing countries have the clout to make strategic decisions during mergers and acquisitions (M&As? This study aims at establishing the major roles played by HR managers in M&As of public sector companies in Ghana. The research examined the M&As of 10 Ghanaian companies where 10 HR managers gave detailed narratives of their roles and the part they played in the M&A processes. The qualitative method used to solicit the narratives of the HR managers resulted in the following findings: that HR managers in Ghana have a limited role in the planning process of the M&A; that indigenous HR managers perform several tasks in the course of the M&A to get employees stable before and after the M&A processes; nevertheless, they are not part of the policy formulators. The article makes a modest input of the significance of indigenous HR role in international M&As as a panacea to solving the global crises by advocating the empowerment of HR managers in developing context to be partners in the initial commencement of M&As.

Short consensus repeat domains extend the E-selectin structure in order to grab cells out of flow

KAUST Repository

Aleisa, Fajr A

2017-01-08

Selectins are key adhesion molecules responsible for initiating a multistep process that leads a cell out of the blood circulation and into a tissue or organ. They are composed of an N-terminal extracellular C-type lectin like domain, followed by an Endothelial Growth Factor like domain (EGF), a defined number of short consensus repeats SCR (also called “sushi” domains), a transmembrane domain and a C-terminal cytoplasmic tail. The adhesion of cells (expressing ligands) to the endothelium (expressing the selection i.e., E-selectin) occurs through the interaction between the lectin domain of selectins and sLeX presenting ligands. Structural/function studies to date have mainly focused on investigating the influence of the lectin domain of E-selectin on its ability to bind its ligands while other domains received less atention. We prepared a number of different recombinant E-selectin proteins with changes in the SCR units. Specifically we generated wild-type E-selectin proteins as monomeric or dimeric structures, mutant proteins with varied numbers of SCRs as well as proteins where strategic residues were mutated to change the conformation of the selectin. Using a novel real time immunoprecipitation surface plasmon resonance (SPR)-based in vitro binding study developed in our lab, the interaction of recombinant E-selectin proteins with immunoprecipitated endogenous ligands (i.e. CD44) captured on a CM-5 chip was assessed. These studies provided quantitative binding kinetics with on and off rates of selectin-ligand interactions and suggested that robust binding is dependent on the presence of the SCRs and oligomerization. These results provide significant implications on the functional mechanism of E-selectin binding to its ligands.

Short consensus repeat domains extend the E-selectin structure in order to grab cells out of flow

KAUST Repository

Aleisa, Fajr A; Sakashita, Kosuke; Lee, Jaeman; Abu Samra, Dina Bashir Kamil; Habuchi, Satoshi; Kusakabe, Takahiro; Merzaban, Jasmeen

2017-01-01

Selectins are key adhesion molecules responsible for initiating a multistep process that leads a cell out of the blood circulation and into a tissue or organ. They are composed of an N-terminal extracellular C-type lectin like domain, followed by an Endothelial Growth Factor like domain (EGF), a defined number of short consensus repeats SCR (also called “sushi” domains), a transmembrane domain and a C-terminal cytoplasmic tail. The adhesion of cells (expressing ligands) to the endothelium (expressing the selection i.e., E-selectin) occurs through the interaction between the lectin domain of selectins and sLeX presenting ligands. Structural/function studies to date have mainly focused on investigating the influence of the lectin domain of E-selectin on its ability to bind its ligands while other domains received less atention. We prepared a number of different recombinant E-selectin proteins with changes in the SCR units. Specifically we generated wild-type E-selectin proteins as monomeric or dimeric structures, mutant proteins with varied numbers of SCRs as well as proteins where strategic residues were mutated to change the conformation of the selectin. Using a novel real time immunoprecipitation surface plasmon resonance (SPR)-based in vitro binding study developed in our lab, the interaction of recombinant E-selectin proteins with immunoprecipitated endogenous ligands (i.e. CD44) captured on a CM-5 chip was assessed. These studies provided quantitative binding kinetics with on and off rates of selectin-ligand interactions and suggested that robust binding is dependent on the presence of the SCRs and oligomerization. These results provide significant implications on the functional mechanism of E-selectin binding to its ligands.

The Chloroplastic Protein THF1 Interacts with the Coiled-Coil Domain of the Disease Resistance Protein N′ and Regulates Light-Dependent Cell Death1[OPEN

Science.gov (United States)

Sekine, Ken-Taro; Wallon, Thérèse; Sugiwaka, Yuji; Kobayashi, Kappei

2016-01-01

One branch of plant immunity is mediated through nucleotide-binding/Leu-rich repeat (NB-LRR) family proteins that recognize specific effectors encoded by pathogens. Members of the I2-like family constitute a well-conserved subgroup of NB-LRRs from Solanaceae possessing a coiled-coil (CC) domain at their N termini. We show here that the CC domains of several I2-like proteins are able to induce a hypersensitive response (HR), a form of programmed cell death associated with disease resistance. Using yeast two-hybrid screens, we identified the chloroplastic protein Thylakoid Formation1 (THF1) as an interacting partner for several I2-like CC domains. Co-immunoprecipitations and bimolecular fluorescence complementation assays confirmed that THF1 and I2-like CC domains interact in planta and that these interactions take place in the cytosol. Several HR-inducing I2-like CC domains have a negative effect on the accumulation of THF1, suggesting that the latter is destabilized by active CC domains. To confirm this model, we investigated N′, which recognizes the coat protein of most Tobamoviruses, as a prototypical member of the I2-like family. Transient expression and gene silencing data indicated that THF1 functions as a negative regulator of cell death and that activation of full-length N′ results in the destabilization of THF1. Consistent with the known function of THF1 in maintaining chloroplast homeostasis, we show that the HR induced by N′ is light-dependent. Together, our results define, to our knowledge, novel molecular mechanisms linking light and chloroplasts to the induction of cell death by a subgroup of NB-LRR proteins. PMID:26951433

Effect of post crosslinking haze on the repeatability of Scheimpflug-based and slit-scanning imaging devices

Directory of Open Access Journals (Sweden)

Rohit Shetty

2017-01-01

Full Text Available Purpose: The aim of this study was to analyze the effect of postcollagen crosslinking (CXL haze on the measurement and repeatability of pachymetry and mean keratometry (Km of four corneal topographers. Materials and Methods: Sixty eyes of sixty patients with progressive keratoconus who had undergone accelerated CXL (ACXL underwent imaging with a scanning slit imaging device (Orbscan II and three Scheimpflug imaging devices (Pentacam HR, Sirius, and Galilei. Post-ACXL haze was measured using the densitometry software on the Pentacam HR. Readings of the thinnest corneal thickness (TCT and Km from three scans of each device were analyzed. Effect of haze on the repeatability of TCT and Km measurements was evaluated using regression models. Repeatability was assessed by coefficient of variation. Results: Corneal densitometry in different zones affected the repeatability of TCT measurement of Orbscan (P < 0.05 significantly but not the repeatability of TCT with Pentacam HR and Sirius (P = 0.03 and 0.05, respectively. Km values were affected by haze when measured with the Pentacam HR (P < 0.05. The repeatability of Km readings for all devices was unaffected by haze. In the anterior 0–2 mm and 2–6 mm zone, TCT (P = 0.43 and 0.45, respectively, Km values (P = 0.4 and 0.6, respectively, repeatability of TCT (P = 0.1 in both zones, and Km (P = 0.5 and 0.1, respectively with Galilei were found to be the most reliable. Conclusion: Galilei measurements appear to be least affected by post-ACXL haze when compared with other devices. Hence, topography measurements in the presence of haze need to be interpreted with caution.

The Chloroplastic Protein THF1 Interacts with the Coiled-Coil Domain of the Disease Resistance Protein N' and Regulates Light-Dependent Cell Death.

Science.gov (United States)

Hamel, Louis-Philippe; Sekine, Ken-Taro; Wallon, Thérèse; Sugiwaka, Yuji; Kobayashi, Kappei; Moffett, Peter

2016-05-01

One branch of plant immunity is mediated through nucleotide-binding/Leu-rich repeat (NB-LRR) family proteins that recognize specific effectors encoded by pathogens. Members of the I2-like family constitute a well-conserved subgroup of NB-LRRs from Solanaceae possessing a coiled-coil (CC) domain at their N termini. We show here that the CC domains of several I2-like proteins are able to induce a hypersensitive response (HR), a form of programmed cell death associated with disease resistance. Using yeast two-hybrid screens, we identified the chloroplastic protein Thylakoid Formation1 (THF1) as an interacting partner for several I2-like CC domains. Co-immunoprecipitations and bimolecular fluorescence complementation assays confirmed that THF1 and I2-like CC domains interact in planta and that these interactions take place in the cytosol. Several HR-inducing I2-like CC domains have a negative effect on the accumulation of THF1, suggesting that the latter is destabilized by active CC domains. To confirm this model, we investigated N', which recognizes the coat protein of most Tobamoviruses, as a prototypical member of the I2-like family. Transient expression and gene silencing data indicated that THF1 functions as a negative regulator of cell death and that activation of full-length N' results in the destabilization of THF1. Consistent with the known function of THF1 in maintaining chloroplast homeostasis, we show that the HR induced by N' is light-dependent. Together, our results define, to our knowledge, novel molecular mechanisms linking light and chloroplasts to the induction of cell death by a subgroup of NB-LRR proteins. © 2016 American Society of Plant Biologists. All Rights Reserved.

Direct and inverted repeats elicit genetic instability by both exploiting and eluding DNA double-strand break repair systems in mycobacteria.

Directory of Open Access Journals (Sweden)

Ewelina A Wojcik

Full Text Available Repetitive DNA sequences with the potential to form alternative DNA conformations, such as slipped structures and cruciforms, can induce genetic instability by promoting replication errors and by serving as a substrate for DNA repair proteins, which may lead to DNA double-strand breaks (DSBs. However, the contribution of each of the DSB repair pathways, homologous recombination (HR, non-homologous end-joining (NHEJ and single-strand annealing (SSA, to this sort of genetic instability is not fully understood. Herein, we assessed the genome-wide distribution of repetitive DNA sequences in the Mycobacterium smegmatis, Mycobacterium tuberculosis and Escherichia coli genomes, and determined the types and frequencies of genetic instability induced by direct and inverted repeats, both in the presence and in the absence of HR, NHEJ, and SSA. All three genomes are strongly enriched in direct repeats and modestly enriched in inverted repeats. When using chromosomally integrated constructs in M. smegmatis, direct repeats induced the perfect deletion of their intervening sequences ~1,000-fold above background. Absence of HR further enhanced these perfect deletions, whereas absence of NHEJ or SSA had no influence, suggesting compromised replication fidelity. In contrast, inverted repeats induced perfect deletions only in the absence of SSA. Both direct and inverted repeats stimulated excision of the constructs from the attB integration sites independently of HR, NHEJ, or SSA. With episomal constructs, direct and inverted repeats triggered DNA instability by activating nucleolytic activity, and absence of the DSB repair pathways (in the order NHEJ>HR>SSA exacerbated this instability. Thus, direct and inverted repeats may elicit genetic instability in mycobacteria by 1 directly interfering with replication fidelity, 2 stimulating the three main DSB repair pathways, and 3 enticing L5 site-specific recombination.

Direct and inverted repeats elicit genetic instability by both exploiting and eluding DNA double-strand break repair systems in mycobacteria.

Science.gov (United States)

Wojcik, Ewelina A; Brzostek, Anna; Bacolla, Albino; Mackiewicz, Pawel; Vasquez, Karen M; Korycka-Machala, Malgorzata; Jaworski, Adam; Dziadek, Jaroslaw

2012-01-01

Repetitive DNA sequences with the potential to form alternative DNA conformations, such as slipped structures and cruciforms, can induce genetic instability by promoting replication errors and by serving as a substrate for DNA repair proteins, which may lead to DNA double-strand breaks (DSBs). However, the contribution of each of the DSB repair pathways, homologous recombination (HR), non-homologous end-joining (NHEJ) and single-strand annealing (SSA), to this sort of genetic instability is not fully understood. Herein, we assessed the genome-wide distribution of repetitive DNA sequences in the Mycobacterium smegmatis, Mycobacterium tuberculosis and Escherichia coli genomes, and determined the types and frequencies of genetic instability induced by direct and inverted repeats, both in the presence and in the absence of HR, NHEJ, and SSA. All three genomes are strongly enriched in direct repeats and modestly enriched in inverted repeats. When using chromosomally integrated constructs in M. smegmatis, direct repeats induced the perfect deletion of their intervening sequences ~1,000-fold above background. Absence of HR further enhanced these perfect deletions, whereas absence of NHEJ or SSA had no influence, suggesting compromised replication fidelity. In contrast, inverted repeats induced perfect deletions only in the absence of SSA. Both direct and inverted repeats stimulated excision of the constructs from the attB integration sites independently of HR, NHEJ, or SSA. With episomal constructs, direct and inverted repeats triggered DNA instability by activating nucleolytic activity, and absence of the DSB repair pathways (in the order NHEJ>HR>SSA) exacerbated this instability. Thus, direct and inverted repeats may elicit genetic instability in mycobacteria by 1) directly interfering with replication fidelity, 2) stimulating the three main DSB repair pathways, and 3) enticing L5 site-specific recombination.

Nonlinear analysis of sequence repeats of multi-domain proteins

Energy Technology Data Exchange (ETDEWEB)

Huang Yanzhao [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Li Mingfeng [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Xiao Yi [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China)]. E-mail: lmf_bill@sina.com

2007-11-15

Many multi-domain proteins have repetitive three-dimensional structures but nearly-random amino acid sequences. In the present paper, by using a modified recurrence plot proposed by us previously, we show that these amino acid sequences have hidden repetitions in fact. These results indicate that the repetitive domain structures are encoded by the repetitive sequences. This also gives a method to detect the repetitive domain structures directly from amino acid sequences.

Crystallization and preliminary X-ray diffraction analysis of central structure domains from mumps virus F protein

International Nuclear Information System (INIS)

Liu, Yueyong; Xu, Yanhui; Zhu, Jieqing; Qiu, Bingsheng; Rao, Zihe; Gao, George F.; Tien, Po

2005-01-01

Single crystals of the central structure domains from mumps virus F protein have been obtained by the hanging-drop vapour-diffusion method. A diffraction data set has been collected to 2.2 Å resolution. Fusion of members of the Paramyxoviridae family involves two glycoproteins: the attachment protein and the fusion protein. Changes in the fusion-protein conformation were caused by binding of the attachment protein to the cellular receptor. In the membrane-fusion process, two highly conserved heptad-repeat (HR) regions, HR1 and HR2, are believed to form a stable six-helix coiled-coil bundle. However, no crystal structure has yet been determined for this state in the mumps virus (MuV, a member of the Paramyxoviridae family). In this study, a single-chain protein consisting of two HR regions connected by a flexible amino-acid linker (named 2-Helix) was expressed, purified and crystallized by the hanging-drop vapour-diffusion method. A complete X-ray data set was obtained in-house to 2.2 Å resolution from a single crystal. The crystal belongs to space group C2, with unit-cell parameters a = 161.2, b = 60.8, c = 40.1 Å, β = 98.4°. The crystal structure will help in understanding the molecular mechanism of Paramyxoviridae family membrane fusion

Repeated anaesthesia with isoflurane and medetomidine-midazolam-fentanyl in guinea pigs and its influence on physiological parameters.

Directory of Open Access Journals (Sweden)

Sabrina Schmitz

Full Text Available Repeated anaesthesia may be required in experimental protocols and in daily veterinary practice, but anaesthesia is known to alter physiological parameters in GPs (Cavia porcellus, GPs. This study investigated the effects of repeated anaesthesia with either medetomidine-midazolam-fentanyl (MMF or isoflurane (Iso on physiological parameters in the GP. Twelve GPs were repeatedly administered with MMF or Iso in two anaesthesia sets. One set consisted of six 40-min anaesthesias, performed over 3 weeks (2 per week; the anaesthetic used first was randomized. Prior to Iso anaesthesia, atropine was injected. MMF anaesthesia was antagonized with AFN (atipamezole-flumazenil-naloxone. Abdominally implanted radio-telemetry devices recorded the mean arterial blood pressure (MAP, heart rate (HR and core body temperature continuously. Additionally, respiratory rate, blood glucose and body weight were assessed. An operable state could be achieved and maintained for 40 min in all GPs. During the surgical tolerance with MMF, the GPs showed a large MAP range between the individuals. In the MMF wake- up phase, the time was shortened until the righting reflex (RR returned and that occurred at lower MAP and HR values. Repeated Iso anaesthesia led to an increasing HR during induction (anaesthesias 2-6, non-surgical tolerance (anaesthesias 3-6 and surgical tolerance (anaesthesias 4, 6. Both anaesthetics may be used repeatedly, as repeating the anaesthesias resulted in only slightly different physiological parameters, compared to those seen with single anaesthesias. The regular atropine premedication induced HR increases and repeated MMF anaesthesia resulted in a metabolism increase which led to the faster return of RR. Nevertheless, Iso's anaesthesia effects of strong respiratory depression and severe hypotension remained. Based on this increased anaesthesia risk with Iso, MMF anaesthesia is preferable for repeated use in GPs.

Digitalisering og HR

DEFF Research Database (Denmark)

Kühn Pedersen, Mogens

2017-01-01

Digitalisering står ligesom HR for et omfattende fag- og praksisfelt. Såvel praksis som teknologiudvikling styrer feltets stadige forandringer.......Digitalisering står ligesom HR for et omfattende fag- og praksisfelt. Såvel praksis som teknologiudvikling styrer feltets stadige forandringer....

Occasioning change through HR sourcing

NARCIS (Netherlands)

van Balen, Mitchell; Bondarouk, Tatiana; Strohmeier, Stefan; Diederichsen, Anke

2010-01-01

This article describes how structuration theory can be used to analyze changes as invoked by two HR Sourcing arrangements: HR Shared Service Centers and HR Outsourcing. This approach allows us to under-stand changing responsibilities, altered HR processes, and the adaptation of web-based tools for

Computational study of the human dystrophin repeats: interaction properties and molecular dynamics.

Directory of Open Access Journals (Sweden)

Baptiste Legrand

Full Text Available Dystrophin is a large protein involved in the rare genetic disease Duchenne muscular dystrophy (DMD. It functions as a mechanical linker between the cytoskeleton and the sarcolemma, and is able to resist shear stresses during muscle activity. In all, 75% of the dystrophin molecule consists of a large central rod domain made up of 24 repeat units that share high structural homology with spectrin-like repeats. However, in the absence of any high-resolution structure of these repeats, the molecular basis of dystrophin central domain's functions has not yet been deciphered. In this context, we have performed a computational study of the whole dystrophin central rod domain based on the rational homology modeling of successive and overlapping tandem repeats and the analysis of their surface properties. Each tandem repeat has very specific surface properties that make it unique. However, the repeats share enough electrostatic-surface similarities to be grouped into four separate clusters. Molecular dynamics simulations of four representative tandem repeats reveal specific flexibility or bending properties depending on the repeat sequence. We thus suggest that the dystrophin central rod domain is constituted of seven biologically relevant sub-domains. Our results provide evidence for the role of the dystrophin central rod domain as a scaffold platform with a wide range of surface features and biophysical properties allowing it to interact with its various known partners such as proteins and membrane lipids. This new integrative view is strongly supported by the previous experimental works that investigated the isolated domains and the observed heterogeneity of the severity of dystrophin related pathologies, especially Becker muscular dystrophy.

Er HR ude i tovene?

DEFF Research Database (Denmark)

Poulfelt, Flemming

2015-01-01

HR: Er der behov for nytænkning i HR-land? Artikler i Harvard Business Review - bakket op af en dansk undersøgelse - konkluderer, at HR stadig mangler gennemslagskraft i virksomhederne. Er HR ude i tovene? ... For i undersøgelsen "Ny Dansk Ledelse" (maj 2015), som er baseret på danske lederes...

Diverticular disease of the colon does not increase risk of repeat C. difficile infection.

Science.gov (United States)

Feuerstadt, Paul; Das, Rohit; Brandt, Lawrence J

2013-01-01

Studies have suggested that colonic diverticulosis might increase the likelihood of repeat Clostridium difficile infection (CDI). Our study was designed to compare rates of repeat infection in patients with and without colon diverticula. Patients who had a positive C. difficile toxin assay and colonoscopic evidence of diverticulosis were classified as CDI and diverticulosis (CDI-D), whereas those with a positive toxin assay but no such colonoscopic evidence were classified as CDI and no diverticulosis (CDI-ND). Various clinical and epidemiologic factors were recorded for each patient. Primary outcomes were "relapse" (repeat CDI within 3 mo of initial infection) and "recurrent" infection (repeat CDI≥3 mo after initial infection). Secondary outcomes 30 days after diagnosis were mortality, intensive care unit transfer, and continuous hospitalization. A total of 128 patients were classified as CDI-D, whereas 137 had CDI-ND. There were no significant differences between CDI-D and CDI-ND when comparing frequencies of repeat infection and its subclassifications, relapse or recurrence. There were, however, statistical associations seen between diverticulosis of the ascending colon and increased recurrence rates [hazard ratio (HR): 1.4±0.38, Pdiverticular disease of the descending (HR: 0.40±0.46, Pcolon (HR: 0.39±0.49, Pcolon association is limited by a small patient population. There were no significant differences in any of the 30-day outcomes including intensive care unit requirement, hospitalization stay, or mortality. Patients with diverticular disease of the colon are not at increased risk of repeat CDI.

Structural and biochemical analysis of nuclease domain of clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 3 (Cas3).

Science.gov (United States)

Mulepati, Sabin; Bailey, Scott

2011-09-09

RNA transcribed from clustered regularly interspaced short palindromic repeats (CRISPRs) protects many prokaryotes from invasion by foreign DNA such as viruses, conjugative plasmids, and transposable elements. Cas3 (CRISPR-associated protein 3) is essential for this CRISPR protection and is thought to mediate cleavage of the foreign DNA through its N-terminal histidine-aspartate (HD) domain. We report here the 1.8 Å crystal structure of the HD domain of Cas3 from Thermus thermophilus HB8. Structural and biochemical studies predict that this enzyme binds two metal ions at its active site. We also demonstrate that the single-stranded DNA endonuclease activity of this T. thermophilus domain is activated not by magnesium but by transition metal ions such as manganese and nickel. Structure-guided mutagenesis confirms the importance of the metal-binding residues for the nuclease activity and identifies other active site residues. Overall, these results provide a framework for understanding the role of Cas3 in the CRISPR system.

Structural determinants at the interface of the ARC2 and leucine-rich repeat domains control the activation of the plant immune receptors Rx1 and Gpa2.

Science.gov (United States)

Slootweg, Erik J; Spiridon, Laurentiu N; Roosien, Jan; Butterbach, Patrick; Pomp, Rikus; Westerhof, Lotte; Wilbers, Ruud; Bakker, Erin; Bakker, Jaap; Petrescu, Andrei-José; Smant, Geert; Goverse, Aska

2013-07-01

Many plant and animal immune receptors have a modular nucleotide-binding-leucine-rich repeat (NB-LRR) architecture in which a nucleotide-binding switch domain, NB-ARC, is tethered to a LRR sensor domain. The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly understood. Here, we report structural determinants governing the interaction between the NB-ARC and LRR in the highly homologous plant immune receptors Gpa2 and Rx1, which recognize the potato cyst nematode Globodera pallida and Potato virus X, respectively. Systematic shuffling of polymorphic sites between Gpa2 and Rx1 showed that a minimal region in the ARC2 and N-terminal repeats of the LRR domain coordinate the activation state of the protein. We identified two closely spaced amino acid residues in this region of the ARC2 (positions 401 and 403) that distinguish between autoactivation and effector-triggered activation. Furthermore, a highly acidic loop region in the ARC2 domain and basic patches in the N-terminal end of the LRR domain were demonstrated to be required for the physical interaction between the ARC2 and LRR. The NB-ARC and LRR domains dissociate upon effector-dependent activation, and the complementary-charged regions are predicted to mediate a fast reassociation, enabling multiple rounds of activation. Finally, we present a mechanistic model showing how the ARC2, NB, and N-terminal half of the LRR form a clamp, which regulates the dissociation and reassociation of the switch and sensor domains in NB-LRR proteins.

Cloning, expression, purification, and characterisation of the HEAT-repeat domain of TOR from the thermophilic eukaryote Chaetomium thermophilum.

Science.gov (United States)

Robinson, Graham C; Vegunta, Yogesh; Gabus, Caroline; Gaubitz, Christl; Thore, Stéphane

2017-05-01

The Target of Rapamycin Complex is a central controller of cell growth and differentiation in eukaryotes. Its global architecture has been described by cryoelectron microscopy, and regions of its central TOR protein have been described by X-ray crystallography. However, the N-terminal region of this protein, which consists of a series of HEAT repeats, remains uncharacterised at high resolution, most likely due to the absence of a suitable purification procedure. Here, we present a robust method for the preparation of the HEAT-repeat domain, utilizing the thermophilic fungus Chaetomium thermophilum as a source organism. We describe construct design and stable expression in insect cells. An efficient two-step purification procedure is presented, and the purified product is characterised by SEC and MALDI-TOF MS. The methods described pave the way for a complete high-resolution characterisation of this elusive region of the TOR protein. Copyright © 2017 Elsevier Inc. All rights reserved.

The perspective of Malaysian Manufacturing Organizations on Strategy, HR Outsourcing and HR Costs

OpenAIRE

Hasliza Abdul HALIM; Norbani CHE-HA

2011-01-01

The paper discusses the relationship between different types of human resource management (HRM) strategy and the human resource outsourcing, and impact on the size of human resource (HR) department. Three HRM strategies are considered: Facilitation, accumulation and utilization. The data for the study were obtained from survey responses from 232 organizations, of which 113 were engaged in HR outsourcing. The findings suggest that organizations tend to rely on outsourcing of HR functions when ...

Screening and identification of T helper 1 and linear immunodominant antibody-binding epitopes in the spike 2 domain and the nucleocapsid protein of feline infectious peritonitis virus.

Science.gov (United States)

Satoh, Ryoichi; Furukawa, Tomoko; Kotake, Masako; Takano, Tomomi; Motokawa, Kenji; Gemma, Tsuyoshi; Watanabe, Rie; Arai, Setsuo; Hohdatsu, Tsutomu

2011-02-17

The antibody-dependent enhancement (ADE) of feline infectious peritonitis virus (FIPV) infection has been recognized in experimentally infected cats, and cellular immunity is considered to play an important role in preventing the onset of feline infectious peritonitis (FIP). In the present study, we synthesized eighty-one kinds of peptides derived from the spike (S)2 domain of type I FIPV KU-2 strain, the S2 domain of type II FIPV 79-1146 strain, and the nucleocapcid (N) protein of FIPV KU-2 strain. To detect the T helper (Th)1 epitope, peripheral blood mononuclear cells (PBMCs) obtained from FIPV-infected cats were cultured with each peptide, and Th1-type immune responses were measured using feline interferon (fIFN)-γ production as an index. To detect the linear immunodominant antibody-binding epitope, we investigated the reactivity of plasma collected from FIPV-infected cats against each peptide by ELISA. Four and 2 peptides containing Th1 epitopes were identified in the heptad repeat (HR)1 and inter-helical (IH) regions of the S2 domain of type I FIPV, respectively, and these were located on the N-terminal side of the regions. In the S2 domain of type II FIPV, 2, 3, and 2 peptides containing Th1 epitopes were identified in the HR1, IH, and HR2 regions, respectively, and these were mainly located on the C-terminal side of the regions. In the S2 domain of type I FIPV, 3 and 7 peptides containing linear immunodominant antibody-binding epitopes were identified in the IH and HR2 regions, respectively. In the S2 domain of type II FIPV, 4 peptides containing linear immunodominant antibody-binding epitopes were identified in the HR2 region. The Th1 epitopes in the S2 domain of type I and II FIPV were located in different regions, but the linear immunodominant antibody-binding epitopes were mostly located in the HR2 region. Eight peptides containing Th1 epitopes were identified in N protein, and 3 peptides derived from residues 81 to 100 and 137 to 164 showed strong

Identification of multiple binding sites for the THAP domain of the Galileo transposase in the long terminal inverted-repeats.

Science.gov (United States)

Marzo, Mar; Liu, Danxu; Ruiz, Alfredo; Chalmers, Ronald

2013-08-01

Galileo is a DNA transposon responsible for the generation of several chromosomal inversions in Drosophila. In contrast to other members of the P-element superfamily, it has unusually long terminal inverted-repeats (TIRs) that resemble those of Foldback elements. To investigate the function of the long TIRs we derived consensus and ancestral sequences for the Galileo transposase in three species of Drosophilids. Following gene synthesis, we expressed and purified their constituent THAP domains and tested their binding activity towards the respective Galileo TIRs. DNase I footprinting located the most proximal DNA binding site about 70 bp from the transposon end. Using this sequence we identified further binding sites in the tandem repeats that are found within the long TIRs. This suggests that the synaptic complex between Galileo ends may be a complicated structure containing higher-order multimers of the transposase. We also attempted to reconstitute Galileo transposition in Drosophila embryos but no events were detected. Thus, although the limited numbers of Galileo copies in each genome were sufficient to provide functional consensus sequences for the THAP domains, they do not specify a fully active transposase. Since the THAP recognition sequence is short, and will occur many times in a large genome, it seems likely that the multiple binding sites within the long, internally repetitive, TIRs of Galileo and other Foldback-like elements may provide the transposase with its binding specificity. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Highly sensitive detection of individual HEAT and ARM repeats with HHpred and COACH.

Science.gov (United States)

Kippert, Fred; Gerloff, Dietlind L

2009-09-24

HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high

The Pentapeptide Repeat Proteins

OpenAIRE

Vetting, Matthew W.; Hegde, Subray S.; Fajardo, J. Eduardo; Fiser, Andras; Roderick, Steven L.; Takiff, Howard E.; Blanchard, John S.

2006-01-01

The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S,T,A,V][D,N][L,F]-[S,T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Myc...

Adding intrapreneurial role in HR business partner model: (an extension in the HR business partner model)

OpenAIRE

Bashir, Jibran; Afzal, Sara

2009-01-01

Purpose: The Purpose of this paper is to introduce a concept, whereby extending the Dave Ulrich’s HR business partner model by adding fifth Role – The HR Intrapreneur Role – in the existing model. This will be done by combining two separate concepts “Four Roles HR Business Partner Model” and “Intrapreneurial HR”, resulting in a five roles HR Business Partner Model. Design/methodology/approach: This paper is introducing a new concept through theoretical research. Findings: H...

RESTORATION TECHNIQUE FOR PLEIADES-HR PANCHROMATIC IMAGES

Directory of Open Access Journals (Sweden)

C. Latry

2012-07-01

Full Text Available 17th of December 2011 from Kourou Space Centre, French Guyana. Like others high resolution optical satellites, it acquires both panchromatic images, with 70cm spatial resolution, and lower resolution multispectral images with 2.8m spatial resolution. Pleiades-HR is an optimized system, which means that the Modulation Transfer Function has a low value at Nyquist frequency, in order to reduce both the telescope diameter and aliasing effects. Shannon sampling condition is thus met at first order, which also makes classical ground processing, such as image matching or resampling, more justified for a mathematical point of view. Raw images are thus blurry which implies a deconvolution stage that restores sharpness but also increases the noise level in the high frequency domain. A denoising step, based upon wavelet packet coefficients thresholding/shrinkage technique, allows controlling the final noise level. Each of these methods includes numerous parameters that have to be assessed during the inflight commissioning period: deconvolution filter that depends on MTF assessment, instrumental noise model, noise level target for denoised images, wavelet packet decomposition level. This paper aims to precisely describe the deconvolution/denoising algorithms and how their main parameters have been set up during the inflight commissioning stage. Special attention will be given to structured noise induced by Pleiades-HR on board wavelet-based compression algorithm

Yeast eIF4B binds to the head of the 40S ribosomal subunit and promotes mRNA recruitment through its N-terminal and internal repeat domains.

Science.gov (United States)

Walker, Sarah E; Zhou, Fujun; Mitchell, Sarah F; Larson, Victoria S; Valasek, Leos; Hinnebusch, Alan G; Lorsch, Jon R

2013-02-01

Eukaryotic translation initiation factor (eIF)4B stimulates recruitment of mRNA to the 43S ribosomal pre-initiation complex (PIC). Yeast eIF4B (yeIF4B), shown previously to bind single-stranded (ss) RNA, consists of an N-terminal domain (NTD), predicted to be unstructured in solution; an RNA-recognition motif (RRM); an unusual domain comprised of seven imperfect repeats of 26 amino acids; and a C-terminal domain. Although the mechanism of yeIF4B action has remained obscure, most models have suggested central roles for its RRM and ssRNA-binding activity. We have dissected the functions of yeIF4B's domains and show that the RRM and its ssRNA-binding activity are dispensable in vitro and in vivo. Instead, our data indicate that the 7-repeats and NTD are the most critical domains, which mediate binding of yeIF4B to the head of the 40S ribosomal subunit via interaction with Rps20. This interaction induces structural changes in the ribosome's mRNA entry channel that could facilitate mRNA loading. We also show that yeIF4B strongly promotes productive interaction of eIF4A with the 43S•mRNA PIC in a manner required for efficient mRNA recruitment.

Radioactive waste legislation. Hearings before the Subcommittee on Energy and the Environment of the Committee on Interior and Insular Affairs, House of Representatives, Ninety-Seventh Congress, First Session on H.R. 1993; H.R. 2800; H.R. 2840; H.R. 2881; H.R. 3809, June 23 and 25; July 9, 1981

International Nuclear Information System (INIS)

Anon.

1981-01-01

This three-day hearing was held to consider five bills on radioactive waste, set priorities for a repository construction program, consider an administration proposal to develop a small-scale test facility for deep permanent storage of high-level wastes, and determine what role the public and private sectors should assume. The hearing record includes the text of H.R. 1993, H.R. 2800, H.R. 2840, H.R. 2881, and H.R. 3809; the statements of 10 witnesses and two panels; and three appendices with additional material submitted for the record

Repeated 24-hour recalls versus dietary records for estimating nutrient intakes in a national food consumption survey

Directory of Open Access Journals (Sweden)

Willem De Keyzer

2011-11-01

Full Text Available The methodology used in the first Belgian food consumption survey followed to a large extent the instructions of the European Food Consumption (EFCOSUM reports, where repeated 24-hour recalls (24HR using EPIC-SOFT were recommended.To evaluate the relative validity of two non-consecutive 24HR using EPIC-SOFT by comparison with 5-day estimated dietary records (EDR. To assess misreporting in energy for both methods by comparing energy intake with energy expenditure from accelerometery in a subsample.A total of 175 subjects (aged 15 and over were recruited to participate in the study. Repeated 24HR were performed with an interval of 2–8 weeks. After completion of the second interview, subjects were instructed to keep an EDR. Dietary intakes were adjusted for within-person variability to reflect usual intakes. A Student's t-test was calculated to assess differences between both methods. Spearman and Kappa correlation coefficients were used to investigate agreement.In total, 127 subjects completed the required repeated 24HR, as well as the five record days. From 76 participants, accelerometer data were available. In both methods, about 35% of participants had ratios of Energy Intake/Total Energy Expenditure (EI/TEE above or below 95% confidence intervals for EI/TEE, suggesting misreporting of energy. Significant differences between the two dietary intake methods were found for total energy, total fat, fatty acids, cholesterol, alcohol, vitamin C, thiamine, riboflavin and iron. In general, intakes from 24HR were higher compared to EDR. Correlation coefficients for all nutrients ranged from 0.16 for thiamine to 0.70 for water.The results from this study show that in the context of nutritional surveillance, duplicate 24HR can be used to asses intakes of protein, carbohydrates, starch, sugar, water, potassium and calcium.

Amino acid substitutions within the heptad repeat domain 1 of murine coronavirus spike protein restrict viral antigen spread in the central nervous system

International Nuclear Information System (INIS)

Tsai, Jean C.; Groot, Linda de; Pinon, Josefina D.; Iacono, Kathryn T.; Phillips, Joanna J.; Seo, Suhun; Lavi, Ehud; Weiss, Susan R.

2003-01-01

Targeted recombination was carried out to select mouse hepatitis viruses (MHVs) in a defined genetic background, containing an MHV-JHM spike gene encoding either three heptad repeat 1 (HR1) substitutions (Q1067H, Q1094H, and L1114R) or L1114R alone. The recombinant virus, which expresses spike with the three substitutions, was nonfusogenic at neutral pH. Its replication was significantly inhibited by lysosomotropic agents, and it was highly neuroattenuated in vivo. In contrast, the recombinant expressing spike with L1114R alone mediated cell-to-cell fusion at neutral pH and replicated efficiently despite the presence of lysosomotropic agents; however, it still caused only subclinical morbidity and no mortality in animals. Thus, both recombinant viruses were highly attenuated and expressed viral antigen which was restricted to the olfactory bulbs and was markedly absent from other regions of the brains at 5 days postinfection. These data demonstrate that amino acid substitutions, in particular L1114R, within HR1 of the JHM spike reduced the ability of MHV to spread in the central nervous system. Furthermore, the requirements for low pH for fusion and viral entry are not prerequisites for the highly attenuated phenotype

Interplay between I308 and Y310 residues in the third repeat of microtubule-binding domain is essential for tau filament formation.

Science.gov (United States)

Naruto, Keiko; Minoura, Katsuhiko; Okuda, Ryouhei; Taniguchi, Taizo; In, Yasuko; Ishida, Toshimasa; Tomoo, Koji

2010-10-08

Investigation of the mechanism of tau polymerization is indispensable for finding inhibitory conditions or identifying compounds preventing the formation of paired helical filament or oligomers. Tau contains a microtubule-binding domain consisting of three or four repeats in its C-terminal half. It has been considered that the key event in tau polymerization is the formation of a β-sheet structure arising from a short hexapeptide (306)VQIVYK(311) in the third repeat of tau. In this paper, we report for the first time that the C-H⋯π interaction between Ile308 and Tyr310 is the elemental structural scaffold essential for forming a dry "steric zipper" structure in tau amyloid fibrils. Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase

Energy Technology Data Exchange (ETDEWEB)

Verardi, Raffaello; Kim, Jin-Sik; Ghirlando, Rodolfo; Banerjee, Anirban

2017-09-01

DHHC enzymes catalyze palmitoylation, a major post-translational modification that regulates a number of key cellular processes. There are up to 24 DHHCs in mammals and hundreds of substrate proteins that get palmitoylated. However, how DHHC enzymes engage with their substrates is still poorly understood. There is currently no structural information about the interaction between any DHHC enzyme and protein substrates. In this study we have investigated the structural and thermodynamic bases of interaction between the ankyrin repeat domain of human DHHC17 (ANK17) and Snap25b. We solved a high-resolution crystal structure of the complex between ANK17 and a peptide fragment of Snap25b. Through structure-guided mutagenesis, we discovered key residues in DHHC17 that are critically important for interaction with Snap25b. We further extended our finding by showing that the same residues are also crucial for the interaction of DHHC17 with Huntingtin, one of its most physiologically relevant substrates.

Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells.

Science.gov (United States)

Choi, Young Eun; Battelli, Chiara; Watson, Jacqueline; Liu, Joyce; Curtis, Jennifer; Morse, Alexander N; Matulonis, Ursula A; Chowdhury, Dipanjan; Konstantinopoulos, Panagiotis A

2014-05-15

The promise of PARP-inhibitors(PARPis) in the management of epithelial ovarian cancer(EOC) is tempered by the fact that approximately 50% of patients with homologous recombination (HR)-proficient tumors do not respond well to these agents. Combination of PARPis with agents that inhibit HR may represent an effective strategy to enhance their activity in HR-proficient tumors. Using a bioinformatics approach, we identified that heat shock protein 90 inhibitors(HSP90i) may suppress HR and thus revert HR-proficient to HR-deficient tumors. Analysis of publicly available gene expression data showed that exposure of HR-proficient breast cancer cell lines to HSP90i 17-AAG(17-allylamino-17-demethoxygeldanamycin) downregulated HR, ATM and Fanconi Anemia pathways. In HR-proficient EOC cells, 17-AAG suppressed HR as assessed using the RAD51 foci formation assay and this was further confirmed using the Direct Repeat-GFP reporter assay. Furthermore, 17-AAG downregulated BRCA1 and/or RAD51 protein levels, and induced significantly more γH2AX activation in combination with olaparib compared to olaparib alone. Finally, sublethal concentrations of 17-AAG sensitized HR-proficient EOC lines to olaparib and carboplatin but did not affect sensitivity of the HR-deficient OVCAR8 line arguing that the 17-AAG mediated sensitization is dependent on suppression of HR. These results provide a preclinical rationale for using a combination of olaparib/17-AAG in HR-proficient EOC.

Designing HR Organizational Structures in terms of the HR Business Partner Model Principles from the Perspective of Czech Organizations

Directory of Open Access Journals (Sweden)

Marek Stříteský

2014-03-01

Full Text Available This paper describes new trends related to the concepts contained in HR organizational structures within Czech organizations. In addition, it describes the specifics of the roles played by HR in those organizations which have transformed their HR departments in terms of the principles of the HR Business Partner Model, both in theory based on available resources, and at the practical level based on the results of primary examination. The goal of this paper is to present the key perceptions of the changes made in the HR structure within the organizations, as well as the impact of these changes on the effectiveness of the HR departments concerned. Another goal of the paper is to summarize the responsibilities of the newly created position known as the HR Business Partner in these organizations as well as the demands placed upon the personnel employed in the HR Business Partner role. The paper offers conclusions based on the results of both quantitative and qualitative surveys. It also contains a case study of one organization which has one of the best transformed HR departments, and whose services are classified, by internal clients, as being of high quality.

Hr Pitt mängib hr Smithi / Timo Diener

Index Scriptorium Estoniae

Diener, Timo

2005-01-01

Brad Pitt actionkomöödias "Hr ja pr Smith" ("Mr and Mrs Smith") : režissöör Doug Liman : Ameerika Ühendriigid 2005. Filmi ümber puhkenud skandaalist ning näitleja plaanitavatest filmirollidest aastal 2006

Random mutagenesis of the nucleotide-binding domain of NRC1 (NB-LRR Required for Hypersensitive Response-Associated Cell Death-1), a downstream signalling nucleotide-binding, leucine-rich repeat (NB-LRR) protein, identifies gain-of-function mutations in the nucleotide-binding pocket

NARCIS (Netherlands)

Sueldo, D.J.; Shimels, M.Z.; Spiridon, L.N.; Caldararu, O.; Petrescu, A.J.; Joosten, M.H.A.J.; Tameling, W.I.L.

2015-01-01

•Plant nucleotide-binding, leucine-rich repeat (NB-LRR) proteins confer immunity to pathogens possessing the corresponding avirulence proteins. Activation of NB-LRR proteins is often associated with induction of the hypersensitive response (HR), a form of programmed cell death. •NRC1 (NB-LRR

Ceramide-Enriched Membrane Domains in Red Blood Cells and the Mechanism ofSphingomyelinase-Induced Hot-Cold Hemolysis

DEFF Research Database (Denmark)

Montes, Ruth; Lopez, David; Sot, Jesus

2008-01-01

Hot-cold hemolysis is the phenomenon whereby red blood cells, preincubated at 37 °C in the presence of certain agents, undergo rapid hemolysis when transferred to 4 °C. The mechanism of this phenomenon is not understood. PlcHR2, a phospholipase C/sphingomyelinase from Pseudomonas aeruginosa......) but also in goat erythrocytes, which lack PC. However, in horse erythrocytes, with a large proportion of PC and almost no SM, hot-cold hemolysis induced by PlcHR2 is not observed. Fluorescence microscopy observations confirm the formation of ceramide-enriched domains as a result of PlcHR2 activity. After......-cold hemolysis. Differential scanning calorimetry of erytrocyte membranes treated with PlcHR2 demonstrates the presence of ceramide-rich domains that are rigid at 4 °C but fluid at 37 °C. Ceramidase treatment causes the disapperance of the calorimetric signal assigned to ceramide-rich domains. Finally...

Impact of retinal pigment epithelium pathology on spectral-domain optical coherence tomography-derived macular thickness and volume metrics and their intersession repeatability.

Science.gov (United States)

Hanumunthadu, Daren; Wang, Jin Ping; Chen, Wei; Wong, Evan N; Chen, Yi; Morgan, William H; Patel, Praveen J; Chen, Fred K

2017-04-01

To determine the impact of retinal pigment epithelium (RPE) pathology on intersession repeatability of retinal thickness and volume metrics derived from Spectralis spectral-domain optical coherence tomography (Heidelberg Engineering, Heidelberg, Germany). Prospective cross-sectional single centre study. A total of 56 eyes of 56 subjects were divided into three groups: (i) normal RPE band (25 eyes); (ii) RPE elevation: macular soft drusen (13 eyes); and (iii) RPE attenuation: geographic atrophy or inherited retinal diseases (18 eyes). Each subject underwent three consecutive follow-up macular raster scans (61 B-scans at 119 μm separation) at 1-month intervals. Retinal thicknesses and volumes for each zone of the macular subfields before and after manual correction of segmentation error. Coefficients of repeatability (CR) were calculated. Mean (range) age was 57 (21-88) years. Mean central subfield thickness (CST) and total macular volume were 264 and 258 μm (P = 0.62), and 8.0 and 7.8 mm 3 (P = 0.31), before and after manual correction. Intersession CR (95% confidence interval) for CST and total macular volume were reduced from 40 (38-41) to 8.3 (8.1-8.5) and 0.62 to 0.16 mm 3 after manual correction of segmentation lines. CR for CST were 7.4, 23.5 and 66.7 μm before and 7.0, 10.9 and 7.6 μm after manual correction in groups i, ii and iii. Segmentation error in eyes with RPE disease has a significant impact on intersession repeatability of Spectralis spectral-domain optical coherence tomography macular thickness and volume metrics. Careful examination of each B-scan and manual adjustment can enhance the utility of quantitative measurement. Improved automated segmentation algorithms are needed. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

Putting HR outsourcing into practice.

Science.gov (United States)

Berger, Michael

2007-01-01

Faced with the time-consuming responsibility of human resources (HR) management, a growing number of medical practices are outsourcing their HR to professional employer organizations (PEOs) so they can concentrate on their core business. A PEO functions as an HR department-minus the high overhead-managing daily administrative tasks such as payroll processing and related tax filings, employee benefits, and workers' compensation coverage and claims resolution. PEOs help physicians' offices keep up with the piles of paperwork that never seem to shrink, freeing doctors to focus on patient care and building their practice. Because of their volume buying power, PEOs are able to offer employees of small medical practices big-company benefits-everything from health, dental, and vision coverage to long-term disability insurance and tuition assistance. A fledgling industry only a decade ago, HR outsourcing has morphed into a blossoming industry. Enlisting the services of a PEO is now considered de rigueur in many small business circles.

To share or not to share: thats the question! When does sharing of HR services maximize perceived HR service value?

NARCIS (Netherlands)

Meijerink, Jeroen Gerard; Hofman, Erwin; Hemels, Hinse

2011-01-01

Nowadays, organizations can rely on a variety of delivery channels for offering HR services to employees, such as HR shared service centres, embedded HR professionals or electronic HRM. However, when should organizations opt for one of the many HR delivery channels that are at their disposal to

Alanine repeats influence protein localization in splicing speckles and paraspeckles.

Science.gov (United States)

Chang, Shuo-Hsiu; Chang, Wei-Lun; Lu, Chia-Chen; Tarn, Woan-Yuh

2014-12-16

Mammalian splicing regulatory protein RNA-binding motif protein 4 (RBM4) has an alanine repeat-containing C-terminal domain (CAD) that confers both nuclear- and splicing speckle-targeting activities. Alanine-repeat expansion has pathological potential. Here we show that the alanine-repeat tracts influence the subnuclear targeting properties of the RBM4 CAD in cultured human cells. Notably, truncation of the alanine tracts redistributed a portion of RBM4 to paraspeckles. The alanine-deficient CAD was sufficient for paraspeckle targeting. On the other hand, alanine-repeat expansion reduced the mobility of RBM4 and impaired its splicing activity. We further took advantage of the putative coactivator activator (CoAA)-RBM4 conjoined splicing factor, CoAZ, to investigate the function of the CAD in subnuclear targeting. Transiently expressed CoAZ formed discrete nuclear foci that emerged and subsequently separated-fully or partially-from paraspeckles. Alanine-repeat expansion appeared to prevent CoAZ separation from paraspeckles, resulting in their complete colocalization. CoAZ foci were dynamic but, unlike paraspeckles, were resistant to RNase treatment. Our results indicate that the alanine-rich CAD, in conjunction with its conjoined RNA-binding domain(s), differentially influences the subnuclear localization and biogenesis of RBM4 and CoAZ. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Rosa26-GFP direct repeat (RaDR-GFP mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo.

Directory of Open Access Journals (Sweden)

Michelle R Sukup-Jackson

2014-06-01

Full Text Available Homologous recombination (HR is critical for the repair of double strand breaks and broken replication forks. Although HR is mostly error free, inherent or environmental conditions that either suppress or induce HR cause genomic instability. Despite its importance in carcinogenesis, due to limitations in our ability to detect HR in vivo, little is known about HR in mammalian tissues. Here, we describe a mouse model in which a direct repeat HR substrate is targeted to the ubiquitously expressed Rosa26 locus. In the Rosa26 Direct Repeat-GFP (RaDR-GFP mice, HR between two truncated EGFP expression cassettes can yield a fluorescent signal. In-house image analysis software provides a rapid method for quantifying recombination events within intact tissues, and the frequency of recombinant cells can be evaluated by flow cytometry. A comparison among 11 tissues shows that the frequency of recombinant cells varies by more than two orders of magnitude among tissues, wherein HR in the brain is the lowest. Additionally, de novo recombination events accumulate with age in the colon, showing that this mouse model can be used to study the impact of chronic exposures on genomic stability. Exposure to N-methyl-N-nitrosourea, an alkylating agent similar to the cancer chemotherapeutic temozolomide, shows that the colon, liver and pancreas are susceptible to DNA damage-induced HR. Finally, histological analysis of the underlying cell types reveals that pancreatic acinar cells and liver hepatocytes undergo HR and also that HR can be specifically detected in colonic somatic stem cells. Taken together, the RaDR-GFP mouse model provides new understanding of how tissue and age impact susceptibility to HR, and enables future studies of genetic, environmental and physiological factors that modulate HR in mammals.

Expression, purification, crystallization and preliminary X-ray diffraction studies of the human keratin 4-binding domain of serine-rich repeat protein 1 from Streptococcus agalactiae

International Nuclear Information System (INIS)

Sundaresan, Ramya; Samen, Ulrike; Ponnuraj, Karthe

2011-01-01

Expression, purification and crystallization of Srr-1-K4BD, a human keratin 4-binding domain of serine-rich repeat protein 1 from S. agalactiae, was carried out. Native crystals of Srr-1-K4BD diffracted to 3.8 Å resolution using synchrotron radiation. Serine-rich repeat protein 1 (Srr-1) is a surface protein from Streptococcus agalactiae. A 17 kDa region of this protein has been identified to bind to human keratin 4 (K4) and is termed the Srr-1 K4-binding domain (Srr-1-K4BD). Recombinant Srr-1-K4BD was overexpressed in Escherichia coli BL21 (DE3) cells. Native and selenomethionine-substituted proteins were prepared using Luria–Bertani (LB) and M9 minimal media, respectively. A two-step purification protocol was carried out to obtain a final homogenous sample of Srr-1-K4BD. Crystals of native Srr-1-K4BD were obtained using PEG 3350 as a precipitant. The crystals diffracted to 3.8 Å resolution using synchrotron radiation and belonged to space group P2 1 , with unit-cell parameters a = 47.56, b = 59.48, c = 94.71 Å, β = 93.95°

Revisiting the TALE repeat.

Science.gov (United States)

Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

2014-04-01

Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

Repeat: a framework to assess empirical reproducibility in biomedical research

Directory of Open Access Journals (Sweden)

Leslie D. McIntosh

2017-09-01

Full Text Available Abstract Background The reproducibility of research is essential to rigorous science, yet significant concerns of the reliability and verifiability of biomedical research have been recently highlighted. Ongoing efforts across several domains of science and policy are working to clarify the fundamental characteristics of reproducibility and to enhance the transparency and accessibility of research. Methods The aim of the proceeding work is to develop an assessment tool operationalizing key concepts of research transparency in the biomedical domain, specifically for secondary biomedical data research using electronic health record data. The tool (RepeAT was developed through a multi-phase process that involved coding and extracting recommendations and practices for improving reproducibility from publications and reports across the biomedical and statistical sciences, field testing the instrument, and refining variables. Results RepeAT includes 119 unique variables grouped into five categories (research design and aim, database and data collection methods, data mining and data cleaning, data analysis, data sharing and documentation. Preliminary results in manually processing 40 scientific manuscripts indicate components of the proposed framework with strong inter-rater reliability, as well as directions for further research and refinement of RepeAT. Conclusions The use of RepeAT may allow the biomedical community to have a better understanding of the current practices of research transparency and accessibility among principal investigators. Common adoption of RepeAT may improve reporting of research practices and the availability of research outputs. Additionally, use of RepeAT will facilitate comparisons of research transparency and accessibility across domains and institutions.

TAIL1: an isthmin-like gene, containing type 1 thrombospondin-repeat and AMOP domain, mapped to ARVD1 critical region.

Science.gov (United States)

Rossi, Valeria; Beffagna, Giorgia; Rampazzo, Alessandra; Bauce, Barbara; Danieli, Gian Antonio

2004-06-23

Isthmins represent a novel family of vertebrate secreted proteins containing one copy of the thrombospondin type 1 repeat (TSR), which in mammals is shared by several proteins with diverse biological functions, including cell adhesion, angiogenesis, and patterning of developing nervous system. We have determined the genomic organization of human TAIL1 (thrombospondin and AMOP containing isthmin-like 1), a novel isthmin-like gene encoding a protein that contains a TSR and a C-terminal AMOP domain (adhesion-associated domain in MUC4 and other proteins), characteristic of extracellular proteins involved in adhesion processes. TAIL1 gene encompasses more than 24.4 kb. Analysis of the DNA sequence surrounding the putative transcriptional start region revealed a TATA-less promoter located in a CpG island. Several consensus binding sites for the transcription factors Sp1 and MZF-1 were identified in this promoter region. In humans, TAIL1 gene is located on chromosome 14q24.3 within ARVD1 (arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 1) critical region; preliminary evidence suggests that it is expressed in several tissues, showing multiple alternative splicing.

Protein domain analysis of genomic sequence data reveals regulation of LRR related domains in plant transpiration in Ficus.

Science.gov (United States)

Lang, Tiange; Yin, Kangquan; Liu, Jinyu; Cao, Kunfang; Cannon, Charles H; Du, Fang K

2014-01-01

Predicting protein domains is essential for understanding a protein's function at the molecular level. However, up till now, there has been no direct and straightforward method for predicting protein domains in species without a reference genome sequence. In this study, we developed a functionality with a set of programs that can predict protein domains directly from genomic sequence data without a reference genome. Using whole genome sequence data, the programming functionality mainly comprised DNA assembly in combination with next-generation sequencing (NGS) assembly methods and traditional methods, peptide prediction and protein domain prediction. The proposed new functionality avoids problems associated with de novo assembly due to micro reads and small single repeats. Furthermore, we applied our functionality for the prediction of leucine rich repeat (LRR) domains in four species of Ficus with no reference genome, based on NGS genomic data. We found that the LRRNT_2 and LRR_8 domains are related to plant transpiration efficiency, as indicated by the stomata index, in the four species of Ficus. The programming functionality established in this study provides new insights for protein domain prediction, which is particularly timely in the current age of NGS data expansion.

Non-contact acquisition of respiration and heart rates using Doppler radar with time domain peak-detection algorithm.

Science.gov (United States)

Xiaofeng Yang; Guanghao Sun; Ishibashi, Koichiro

2017-07-01

The non-contact measurement of the respiration rate (RR) and heart rate (HR) using a Doppler radar has attracted more attention in the field of home healthcare monitoring, due to the extremely low burden on patients, unconsciousness and unconstraint. Most of the previous studies have performed the frequency-domain analysis of radar signals to detect the respiration and heartbeat frequency. However, these procedures required long period time (approximately 30 s) windows to obtain a high-resolution spectrum. In this study, we propose a time-domain peak detection algorithm for the fast acquisition of the RR and HR within a breathing cycle (approximately 5 s), including inhalation and exhalation. Signal pre-processing using an analog band-pass filter (BPF) that extracts respiration and heartbeat signals was performed. Thereafter, the HR and RR were calculated using a peak position detection method, which was carried out via LABVIEW. To evaluate the measurement accuracy, we measured the HR and RR of seven subjects in the laboratory. As a reference of HR and RR, the persons wore contact sensors i.e., an electrocardiograph (ECG) and a respiration band. The time domain peak-detection algorithm, based on the Doppler radar, exhibited a significant correlation coefficient of HR of 0.92 and a correlation coefficient of RR of 0.99, between the ECG and respiration band, respectively.

HR competencies at a merged Higher Education Institution

Directory of Open Access Journals (Sweden)

Cecile M. Schultz

2010-06-01

Research purposes: The aim of this study was to determine the HR competencies at a merged higher education institution. Other objectives were to establish the satisfaction of academics, administrative staff and management regarding the HR competencies and the importance thereof. Motivation for the study: Human resource professionals require assistance by providing HR competencies necessary to add value at a merged higher education institution. Research designs, approaches and methods: A quantitative research design was employed as the research strategy. The questionnaire was based on the literature, the business plan and the HR balanced scorecard report. The target population was 1363 permanent staff on one campus and the response rate was 28%. A principal factor analysis, spider charts and box plots were utilised for data analysis. The results indicated business knowledge, HR practices, personal skills and management skills as the vital HR competencies. Practical implications: Staff were not satisfied with the current HR competencies and consequently this necessitated attention to improve the deficient areas. Contribution: This study shows that limited research was done with regard to HR competencies in the South African higher education backdrop.

Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity.

Science.gov (United States)

Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; Mota, Glória de Fátima Alves da; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

2018-01-01

Previous studies have linked angiotensin-converting enzyme ( ACE) insertion (I)/deletion (D) polymorphism (II, ID and DD) to physical performance. Moreover, ACE has two catalytic domains: NH2 (N) and COOH (C) with distinct functions, and their activity has been found to be modulated by ACE polymorphism. The aim of the present study is to investigate the effects of the interaction between aerobic exercise training (AET) and ACE I/D polymorphism on ACE N- and C-domain activities and vascular reactivity in humans. A total of 315 pre-selected healthy males were genotyped for II, ID and DD genotypes. Fifty completed the full AET (II, n = 12; ID, n = 25; and DD, n = 13), performed in three 90-minute sessions weekly, in the four-month exercise protocol. Pre- and post-training resting heart rate (HR), peak O 2 consumption (VO 2 peak), mean blood pressure (MBP), forearm vascular conduction (FVC), total circulating ACE and C- and N-domain activities were assessed. One-way ANOVA and two -way repeated-measures ANOVA were used. In pre-training, all variables were similar among the three genotypes. In post-training, a similar increase in FVC (35%) was observed in the three genotypes. AET increased VO 2 peak similarly in II, ID and DD (49±2 vs. 57±1; 48±1 vs. 56±3; and 48±5 vs. 58±2 ml/kg/min, respectively). Moreover, there were no changes in HR and MBP. The DD genotype was also associated with greater ACE and C-domain activities at pre- and post-training when compared to II. AET decreased similarly the total ACE and C-domain activities in all genotypes, while increasing the N-domain activity in the II and DD genotypes. However, interestingly, the measurements of N-domain activity after training indicate a greater activity than the other genotypes. These results suggest that the vasodilation in response to AET may be associated with the decrease in total ACE and C-domain activities, regardless of genotype, and that the increase in N-domain activity is dependent on the DD

A versatile palindromic amphipathic repeat coding sequence horizontally distributed among diverse bacterial and eucaryotic microbes

Directory of Open Access Journals (Sweden)

Glass John I

2010-07-01

Full Text Available Abstract Background Intragenic tandem repeats occur throughout all domains of life and impart functional and structural variability to diverse translation products. Repeat proteins confer distinctive surface phenotypes to many unicellular organisms, including those with minimal genomes such as the wall-less bacterial monoderms, Mollicutes. One such repeat pattern in this clade is distributed in a manner suggesting its exchange by horizontal gene transfer (HGT. Expanding genome sequence databases reveal the pattern in a widening range of bacteria, and recently among eucaryotic microbes. We examined the genomic flux and consequences of the motif by determining its distribution, predicted structural features and association with membrane-targeted proteins. Results Using a refined hidden Markov model, we document a 25-residue protein sequence motif tandemly arrayed in variable-number repeats in ORFs lacking assigned functions. It appears sporadically in unicellular microbes from disparate bacterial and eucaryotic clades, representing diverse lifestyles and ecological niches that include host parasitic, marine and extreme environments. Tracts of the repeats predict a malleable configuration of recurring domains, with conserved hydrophobic residues forming an amphipathic secondary structure in which hydrophilic residues endow extensive sequence variation. Many ORFs with these domains also have membrane-targeting sequences that predict assorted topologies; others may comprise reservoirs of sequence variants. We demonstrate expressed variants among surface lipoproteins that distinguish closely related animal pathogens belonging to a subgroup of the Mollicutes. DNA sequences encoding the tandem domains display dyad symmetry. Moreover, in some taxa the domains occur in ORFs selectively associated with mobile elements. These features, a punctate phylogenetic distribution, and different patterns of dispersal in genomes of related taxa, suggest that the

Repeat-containing protein effectors of plant-associated organisms

Directory of Open Access Journals (Sweden)

Carl H. Mesarich

2015-10-01

Full Text Available Many plant-associated organisms, including microbes, nematodes, and insects, deliver effector proteins into the apoplast, vascular tissue, or cell cytoplasm of their prospective hosts. These effectors function to promote colonization, typically by altering host physiology or by modulating host immune responses. The same effectors however, can also trigger host immunity in the presence of cognate host immune receptor proteins, and thus prevent colonization. To circumvent effector-triggered immunity, or to further enhance host colonization, plant-associated organisms often rely on adaptive effector evolution. In recent years, it has become increasingly apparent that several effectors of plant-associated organisms are repeat-containing proteins (RCPs that carry tandem or non-tandem arrays of an amino acid sequence or structural motif. In this review, we highlight the diverse roles that these repeat domains play in RCP effector function. We also draw attention to the potential role of these repeat domains in adaptive evolution with regards to RCP effector function and the evasion of effector-triggered immunity. The aim of this review is to increase the profile of RCP effectors from plant-associated organisms.

Learning and Development Policy available on HR web

CERN Multimedia

2012-01-01

The full text of CERN’s “Learning and Development Policy” is now available in English and French on the HR training website: cern.ch/hr-training/. This new policy was presented to all personnel in the HR Public meeting held on Monday 25 June, and the slides and the video recording remain available on Indico. Pascale Goy, Head of the Learning and Development Group in HR, is available for more information: pascale.goy@cern.ch , tel. 62232.

Rotational and translational distortions of the crystal structure of the Sr2HrRuO6 (Hr = Ho, Dy, Gd, Eu) complex perovskites

International Nuclear Information System (INIS)

Triana, C.A.; Landínez Téllez, D.A.; Roa-Rojas, J.

2013-01-01

Sr 2 HrRuO 6 (Hr = Ho, Dy, Gd, Eu) complex perovskites were synthesized through the high-temperature solid-state reaction method, and their crystal structures were analyzed in detail as a function of the Hr-cation ionic radius. Results of powder XRD pattern measurement and Rietveld analysis of the experimental profiles show that the Sr 2 HrRuO 6 compounds crystallize in a monoclinic distorted perovskite-like structure, P2 1 /n (#14) space group, where the unit cell parameters are related to the primitive unit cell a p by a≈√(2)a p , b≈√(2)a p and c ≈ 2a p . The structures show an alternate distribution of the Ru 5+ (2d: 0.5, 0, 0) and Hr 3+ (2c: 0, 0.5, 0) making up RuO 6 and HrO 6 octahedra alternatively arranged in two interleaving fcc sublattices, where the O(1), O(2), and O(3) ions are localized at the corner of the octahedral, while the Sr 2+ is located at the A-site, occupying the cavities built by the corner-sharing octahedra with Wyckoff position 4e. Due to the existence of mismatched ionic sizes between the ionic radii of the Sr 2 HrRuO 6 compounds, the HrO 6 and RuO 6 octahedra are constrained to tilting around the [111] c , [001] c , and [110] c cubic directions so as to optimize the Sr–O inter-atomic bond lengths, tending to rotate the structure in order to fix the Ru 5+ and Hr 3+ ions on the M′ and M″ sites of the complex perovskites. The cell parameters a, b, and c, the inter-atomic bond angles, the inter-atomic bond lengths, and the tilting angles increase as the Hr-cation ionic radius increases. The mismatch that exists in the Sr 2 HrRuO 6 ionic radius produces a large distortion from the ideal cubic symmetry. The pure perovskite-like phase of Sr 2 HrRuO 6 is thermodynamically and kinetically stable at high temperatures above 1420 K, where it is entirely governed by the average size of the Hr 3+ and Ru 5+ cations. Highlights: ► Crystal structure of Sr 2 HrRuO 6 (Hr = Ho, Dy, Gd, Eu) as a function of Hr ionic radius. ► XRD

Global trends and challenges to the HR profession.

OpenAIRE

Prouska, Rea; Cooke, Fang Lee.

2006-01-01

The outsourcing of HR activities is a management strategy that may be adopted in response to a number of pressures that an organization is faced with. It is one aspect of business process outsourcing that is increasingly deployed by firms in order to enhance their organizational competitiveness. HR outsourcing can be defined as ‘placing responsibility for various elements of the HR function with a third-party provider’ (Turnbull, 2002, p.11). In spite of the perceived benefits of HR outsourci...

Peptides corresponding to the predicted heptad repeat 2 domain of the feline coronavirus spike protein are potent inhibitors of viral infection.

Directory of Open Access Journals (Sweden)

I-Jung Liu

Full Text Available BACKGROUND: Feline infectious peritonitis (FIP is a lethal immune-mediated disease caused by feline coronavirus (FCoV. Currently, no therapy with proven efficacy is available. In searching for agents that may prove clinically effective against FCoV infection, five analogous overlapping peptides were designed and synthesized based on the putative heptad repeat 2 (HR2 sequence of the spike protein of FCoV, and the antiviral efficacy was evaluated. METHODS: Plaque reduction assay and MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide cytotoxicity assay were performed in this study. Peptides were selected using a plaque reduction assay to inhibit Feline coronavirus infection. RESULTS: The results demonstrated that peptide (FP5 at concentrations below 20 μM inhibited viral replication by up to 97%. The peptide (FP5 exhibiting the most effective antiviral effect was further combined with a known anti-viral agent, human interferon-α (IFN-α, and a significant synergistic antiviral effect was observed. CONCLUSION: Our data suggest that the synthetic peptide FP5 could serve as a valuable addition to the current FIP prevention methods.

The effect of single and repeated UVB radiation on rabbit cornea.

Science.gov (United States)

Fris, Miroslav; Tessem, May-Britt; Cejková, Jitka; Midelfart, Anna

2006-12-01

Cumulative effect of ultraviolet radiation (UVR) is an important aspect of UV corneal damage. The purpose of this study was to apply high resolution magic angle spinning proton nuclear magnetic resonance (HR-MAS 1H NMR) spectroscopy to evaluate the effect of single and repeated UV radiation exposure of the same overall dose on the rabbit cornea. Corneal surfaces of 24 normal rabbit eyes were examined for the effects of UVB exposure (312 nm). In the first group (UVB1), animals were irradiated with a single dose (3.12 J/cm2; 21 min) of UVB radiation. The animals in the second group (UVB2) were irradiated three times for 7 min every other day (dose of 1.04 J/cm2; days 1, 3, 5) to give the same overall dose (3.12 J/cm2). The third group served as an untreated control group. One day after the last irradiation, the animals were sacrificed, and the corneas were removed and frozen. HR-MAS 1H NMR spectra from intact corneas were obtained. Special grouping patterns among the tissue samples and the relative percentage changes in particular metabolite concentrations were evaluated using modern statistical methods (multivariate analysis, one-way ANOVA). The metabolic profile of both groups of UVB-irradiated samples was significantly different from the control corneas. Substantial decreases in taurine, hypo-taurine and choline-derivatives concentrations and substantial elevation in glucose and betaine levels were observed following the UVR exposure. There was no significant difference between the effect of a single and repeated UVB irradiation of the same overall dose. For the first time, the effects of single and repeated UVR doses on the metabolic profile of the rabbit cornea were analysed and compared. The combination of HR-MAS 1H NMR spectroscopy and modern statistical methods (multivariate analysis, one-way ANOVA) proved suitable to assess the overall view of the metabolic alterations in the rabbit corneal tissue following UVB radiation exposure.

Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

Directory of Open Access Journals (Sweden)

Guan-Feng Wang

2015-02-01

Full Text Available Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR. Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC, a nucleotide binding (NB-ARC and a leucine rich repeat (LRR domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

Science.gov (United States)

Wang, Guan-Feng; Ji, Jiabing; El-Kasmi, Farid; Dangl, Jeffery L; Johal, Guri; Balint-Kurti, Peter J

2015-02-01

Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR) proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR). Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC), a nucleotide binding (NB-ARC) and a leucine rich repeat (LRR) domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

APE1 incision activity at abasic sites in tandem repeat sequences.

Science.gov (United States)

Li, Mengxia; Völker, Jens; Breslauer, Kenneth J; Wilson, David M

2014-05-29

Repetitive DNA sequences, such as those present in microsatellites and minisatellites, telomeres, and trinucleotide repeats (linked to fragile X syndrome, Huntington disease, etc.), account for nearly 30% of the human genome. These domains exhibit enhanced susceptibility to oxidative attack to yield base modifications, strand breaks, and abasic sites; have a propensity to adopt non-canonical DNA forms modulated by the positions of the lesions; and, when not properly processed, can contribute to genome instability that underlies aging and disease development. Knowledge on the repair efficiencies of DNA damage within such repetitive sequences is therefore crucial for understanding the impact of such domains on genomic integrity. In the present study, using strategically designed oligonucleotide substrates, we determined the ability of human apurinic/apyrimidinic endonuclease 1 (APE1) to cleave at apurinic/apyrimidinic (AP) sites in a collection of tandem DNA repeat landscapes involving telomeric and CAG/CTG repeat sequences. Our studies reveal the differential influence of domain sequence, conformation, and AP site location/relative positioning on the efficiency of APE1 binding and strand incision. Intriguingly, our data demonstrate that APE1 endonuclease efficiency correlates with the thermodynamic stability of the DNA substrate. We discuss how these results have both predictive and mechanistic consequences for understanding the success and failure of repair protein activity associated with such oxidatively sensitive, conformationally plastic/dynamic repetitive DNA domains. Published by Elsevier Ltd.

Conservation of the human integrin-type beta-propeller domain in bacteria.

Directory of Open Access Journals (Sweden)

Bhanupratap Chouhan

Full Text Available Integrins are heterodimeric cell-surface receptors with key functions in cell-cell and cell-matrix adhesion. Integrin α and β subunits are present throughout the metazoans, but it is unclear whether the subunits predate the origin of multicellular organisms. Several component domains have been detected in bacteria, one of which, a specific 7-bladed β-propeller domain, is a unique feature of the integrin α subunits. Here, we describe a structure-derived motif, which incorporates key features of each blade from the X-ray structures of human αIIbβ3 and αVβ3, includes elements of the FG-GAP/Cage and Ca(2+-binding motifs, and is specific only for the metazoan integrin domains. Separately, we searched for the metazoan integrin type β-propeller domains among all available sequences from bacteria and unicellular eukaryotic organisms, which must incorporate seven repeats, corresponding to the seven blades of the β-propeller domain, and so that the newly found structure-derived motif would exist in every repeat. As the result, among 47 available genomes of unicellular eukaryotes we could not find a single instance of seven repeats with the motif. Several sequences contained three repeats, a predicted transmembrane segment, and a short cytoplasmic motif associated with some integrins, but otherwise differ from the metazoan integrin α subunits. Among the available bacterial sequences, we found five examples containing seven sequential metazoan integrin-specific motifs within the seven repeats. The motifs differ in having one Ca(2+-binding site per repeat, whereas metazoan integrins have three or four sites. The bacterial sequences are more conserved in terms of motif conservation and loop length, suggesting that the structure is more regular and compact than those example structures from human integrins. Although the bacterial examples are not full-length integrins, the full-length metazoan-type 7-bladed β-propeller domains are present, and

Quantitative in vivo HR-pQCT imaging of 3D wrist and metacarpophalangeal joint space width in rheumatoid arthritis.

Science.gov (United States)

Burghardt, Andrew J; Lee, Chan Hee; Kuo, Daniel; Majumdar, Sharmila; Imboden, John B; Link, Thomas M; Li, Xiaojuan

2013-12-01

In this technique development study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was applied to non-invasively image and quantify 3D joint space morphology of the wrist and metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA). HR-pQCT imaging (82 μm voxel-size) of the dominant hand was performed in patients with diagnosed rheumatoid arthritis (RA, N = 16, age: 52.6 ± 12.8) and healthy controls (CTRL, N = 7, age: 50.1 ± 15.0). An automated computer algorithm was developed to segment wrist and MCP joint spaces. The 3D distance transformation method was applied to spatially map joint space width, and summarized by the mean joint space width (JSW), minimal and maximal JSW (JSW.MIN, JSW.MAX), asymmetry (JSW.AS), and distribution (JSW.SD)-a measure of joint space heterogeneity. In vivo precision was determined for each measure by calculating the smallest detectable difference (SDD) and root mean square coefficient of variation (RMSCV%) of repeat scans. Qualitatively, HR-pQCT images and pseudo-color JSW maps showed global joint space narrowing, as well as regional and focal abnormalities in RA patients. In patients with radiographic JSN at an MCP, JSW.SD was two-fold greater vs. CTRL (p 3D joint space morphology from HR-pQCT, could improve early detection of joint damage in rheumatological diseases.

Do line managers’ have ‘linking pin’ in HR roles?

Directory of Open Access Journals (Sweden)

Mohamed Ayyub Hassan

2015-01-01

Full Text Available Purpose: The present article aims to identify the possible line managers’ involvement factors in human resource (HR initiatives and its ‘linking pin’ to the HR roles. In this regard, few factors have been considered pertinent to line managers’ involvement factors in HR initiatives which are desire, self-efficacy, and HR support. Whereas, the considered dimensions of HR roles reviewed are strategic partner, change agent, employee champion, and administrative expert. Design/methodology/approach: The paper intends to provide a conceptual review of the past literature in the areas of HR roles and line managers and further justify the proposed conceptual framework that will move this work further. Findings: The review also showed that HR devolution to line managers will boost line managers’ participation and responsibility to practice HR roles at the workplace. Research limitations/implications: The main limitation of this review is no empirical evidence provided by the authors to support the literature of the article. All the provided literature is written based on the findings gained from the previous studies. Practical implications: Line managers’ involvement in HR Initiatives can increase the competency diversity among line manager. This in turn can help the organization to operate at high efficiency. Originality/value: There is a notable lack of research conducted to identify line managers’ involvement in HR. Therefore, this article contributes to the literature on the relationship between line managers and HR roles.

FACILITATING RADICAL FRONT-END INNOVATION THROUGH TARGETED HR PRACTICES

DEFF Research Database (Denmark)

Aagaard, Annabeth

2017-01-01

This study examines how radical front end innovation can be actively facilitated through selected and targeted HR practices and bundles of HR practices. The empirical field is an explorative case study of front end innovation and HR practices in the pharmaceutical industry, with an in-depth case ...

Positive selection in the leucine-rich repeat domain of Gro1 genes in ...

Indian Academy of Sciences (India)

history during which the main structure of the domain has been conserved such that ... from the column using 100 μL of distilled water. The LRR fragments from the ... ture of the domain and to obtain the best PDB template for mapping positive ...

Distribution and Evolution of Yersinia Leucine-Rich Repeat Proteins

Science.gov (United States)

Hu, Yueming; Huang, He; Hui, Xinjie; Cheng, Xi; White, Aaron P.

2016-01-01

Leucine-rich repeat (LRR) proteins are widely distributed in bacteria, playing important roles in various protein-protein interaction processes. In Yersinia, the well-characterized type III secreted effector YopM also belongs to the LRR protein family and is encoded by virulence plasmids. However, little has been known about other LRR members encoded by Yersinia genomes or their evolution. In this study, the Yersinia LRR proteins were comprehensively screened, categorized, and compared. The LRR proteins encoded by chromosomes (LRR1 proteins) appeared to be more similar to each other and different from those encoded by plasmids (LRR2 proteins) with regard to repeat-unit length, amino acid composition profile, and gene expression regulation circuits. LRR1 proteins were also different from LRR2 proteins in that the LRR1 proteins contained an E3 ligase domain (NEL domain) in the C-terminal region or an NEL domain-encoding nucleotide relic in flanking genomic sequences. The LRR1 protein-encoding genes (LRR1 genes) varied dramatically and were categorized into 4 subgroups (a to d), with the LRR1a to -c genes evolving from the same ancestor and LRR1d genes evolving from another ancestor. The consensus and ancestor repeat-unit sequences were inferred for different LRR1 protein subgroups by use of a maximum parsimony modeling strategy. Structural modeling disclosed very similar repeat-unit structures between LRR1 and LRR2 proteins despite the different unit lengths and amino acid compositions. Structural constraints may serve as the driving force to explain the observed mutations in the LRR regions. This study suggests that there may be functional variation and lays the foundation for future experiments investigating the functions of the chromosomally encoded LRR proteins of Yersinia. PMID:27217422

THICKNESS OF THE MACULA, RETINAL NERVE FIBER LAYER, AND GANGLION CELL-INNER PLEXIFORM LAYER IN THE AGE-RELATED MACULAR DEGENERATION: The Repeatability Study of Spectral Domain Optical Coherence Tomography.

Science.gov (United States)

Shin, Il-Hwan; Lee, Woo-Hyuk; Lee, Jong-Joo; Jo, Young-Joon; Kim, Jung-Yeul

2018-02-01

To determine the repeatability of measuring the thickness of the central macula, retinal nerve fiber layer, and ganglion cell-inner plexiform layer (GC-IPL) using spectral domain optical coherence tomography (Cirrus HD-OCT) in eyes with age-related macular degeneration. One hundred and thirty-four eyes were included. The measurement repeatability was assessed by an experienced examiner who performed two consecutive measurements using a 512 × 128 macular cube scan and a 200 × 200 optic disk cube scan. To assess changes in macular morphology in patients with age-related macular degeneration, the patients were divided into the following three groups according to the central macular thickness (CMT): A group, CMT 300 μm. Measurement repeatability was assessed using test-retest variability, a coefficient of variation, and an intraclass correlation coefficient. The mean measurement repeatability for the central macular, retinal nerve fiber layer, and GC-IPL thickness was high in the B group. The mean measurement repeatability for both the central macula and retinal nerve fiber layer thickness was high in the A and C groups, but was lower for the GC-IPL thickness. The measurement repeatability for GC-IPL thickness was high in the B group, but low in the A group and in the C group. The automated measurement repeatability for GC-IPL thickness was significantly lower in patients with age-related macular degeneration with out of normal CMT range. The effect of changes in macular morphology should be considered when analyzing GC-IPL thicknesses in a variety of ocular diseases.

Studies on the intracellular localization of hHR23B

International Nuclear Information System (INIS)

Katiyar, Samiksha; Lennarz, William J.

2005-01-01

Yeast Rad23, originally identified as a DNA repair protein, has been proposed to participate in other cellular functions, i.e., the proteasome-degradation pathway, the process of spindle pole body duplication and as a component of the anaphase checkpoint. Two human homologs of yeast Rad23, hHR23A and hHR23B, exhibit high sequence homology with yRad23 and also have been shown to be involved in DNA repair and proteasome-dependent degradation. Previous studies on the intracellular localization of hHR23A and hHR23B revealed their predominant localization in the nucleus during interphase and in the cytoplasm during mitosis. We have analyzed the localization of hHR23B during all the phases of the cell cycle using immunofluorescence. Unlike previous studies, our results suggest localization of hHR23B in the nucleus as well as in the cytoplasm during G1 phase. The nuclear levels of hHR23B decrease during S-phase of the cell cycle. When the cell enters mitosis, hHR23B relocalizes in the cytoplasm without association with chromatin. These results indicate that the intracellular distribution hHR23B is cell cycle dependent

Comparison of the carboxy-terminal DP-repeat region in the co-chaperones Hop and Hip.

Science.gov (United States)

Nelson, Gregory M; Huffman, Holly; Smith, David F

2003-01-01

Functional steroid receptor complexes are assembled and maintained by an ordered pathway of interactions involving multiple components of the cellular chaperone machinery. Two of these components, Hop and Hip, serve as co-chaperones to the major heat shock proteins (Hsps), Hsp70 and Hsp90, and participate in intermediate stages of receptor assembly. In an effort to better understand the functions of Hop and Hip in the assembly process, we focused on a region of similarity located near the C-terminus of each co-chaperone. Contained within this region is a repeated sequence motif we have termed the DP repeat. Earlier mutagenesis studies implicated the DP repeat of either Hop or Hip in Hsp70 binding and in normal assembly of the co-chaperones with progesterone receptor (PR) complexes. We report here that the DP repeat lies within a protease-resistant domain that extends to or is near the C-terminus of both co-chaperones. Point mutations in the DP repeats render the C-terminal regions hypersensitive to proteolysis. In addition, a Hop DP mutant displays altered proteolytic digestion patterns, which suggest that the DP-repeat region influences the folding of other Hop domains. Although the respective DP regions of Hop and Hip share sequence and structural similarities, they are not functionally interchangeable. Moreover, a double-point mutation within the second DP-repeat unit of Hop that converts this to the sequence found in Hip disrupts Hop function; however, the corresponding mutation in Hip does not alter its function. We conclude that the DP repeats are important structural elements within a C-terminal domain, which is important for Hop and Hip function.

Rotational and translational distortions of the crystal structure of the Sr{sub 2}HrRuO{sub 6} (Hr = Ho, Dy, Gd, Eu) complex perovskites

Energy Technology Data Exchange (ETDEWEB)

Triana, C.A., E-mail: ctrianae@unal.edu.co [Grupo de Física de Nuevos Materiales, Departamento de Física, Universidad Nacional de Colombia, A.A. 5997, Bogotá D.C. (Colombia); Landínez Téllez, D.A. [Grupo de Física de Nuevos Materiales, Departamento de Física, Universidad Nacional de Colombia, A.A. 5997, Bogotá D.C. (Colombia); Roa-Rojas, J., E-mail: jroar@unal.edu.co [Grupo de Física de Nuevos Materiales, Departamento de Física, Universidad Nacional de Colombia, A.A. 5997, Bogotá D.C. (Colombia)

2013-05-15

Sr{sub 2}HrRuO{sub 6} (Hr = Ho, Dy, Gd, Eu) complex perovskites were synthesized through the high-temperature solid-state reaction method, and their crystal structures were analyzed in detail as a function of the Hr-cation ionic radius. Results of powder XRD pattern measurement and Rietveld analysis of the experimental profiles show that the Sr{sub 2}HrRuO{sub 6} compounds crystallize in a monoclinic distorted perovskite-like structure, P2{sub 1}/n (#14) space group, where the unit cell parameters are related to the primitive unit cell a{sub p} by a≈√(2)a{sub p}, b≈√(2)a{sub p} and c ≈ 2a{sub p}. The structures show an alternate distribution of the Ru{sup 5+} (2d: 0.5, 0, 0) and Hr{sup 3+} (2c: 0, 0.5, 0) making up RuO{sub 6} and HrO{sub 6} octahedra alternatively arranged in two interleaving fcc sublattices, where the O(1), O(2), and O(3) ions are localized at the corner of the octahedral, while the Sr{sup 2+} is located at the A-site, occupying the cavities built by the corner-sharing octahedra with Wyckoff position 4e. Due to the existence of mismatched ionic sizes between the ionic radii of the Sr{sub 2}HrRuO{sub 6} compounds, the HrO{sub 6} and RuO{sub 6} octahedra are constrained to tilting around the [111]{sub c}, [001]{sub c}, and [110]{sub c} cubic directions so as to optimize the Sr–O inter-atomic bond lengths, tending to rotate the structure in order to fix the Ru{sup 5+} and Hr{sup 3+} ions on the M′ and M″ sites of the complex perovskites. The cell parameters a, b, and c, the inter-atomic bond angles, the inter-atomic bond lengths, and the tilting angles increase as the Hr-cation ionic radius increases. The mismatch that exists in the Sr{sub 2}HrRuO{sub 6} ionic radius produces a large distortion from the ideal cubic symmetry. The pure perovskite-like phase of Sr{sub 2}HrRuO{sub 6} is thermodynamically and kinetically stable at high temperatures above 1420 K, where it is entirely governed by the average size of the Hr{sup 3+} and Ru

[Knocking-out extra domain A alternative splice fragment of fibronectin using a clustered regularly interspaced short palindromic repeats/associated proteins 9 system].

Science.gov (United States)

Yang, Yue; Wang, Haicheng; Xu, Shuyu; Peng, Jing; Jiang, Jiuhui; Li, Cuiying

2015-08-01

To investigate the effect of the fibronectin extra domain A on the aggressiveness of salivary adenoid cystic carcinoma (SACC) cells, via the clustered regularly interspaced short palindromic repeats (CRISPR)/ associated proteins (Cas) system. One sgRNA was designed to target the upstream of the genome sequences of extra domain A(EDA) exon and the downstream. Then the sgRNA was linked into plasmid PX-330 and transfected into SACC-83 cells. PCR and DNA sequence were used to testify the knockout cells, and the monoclones of EDA absent SACC cells were selected (A+C-2, A+C-6, B+C-10). CCK-8 cell proliferation and invasion was then tested in control group and the experimental group. The sgRNA was successfully linked into PX-330 plasmid. Part of adenoid cystic carcinoma cells' SACC-83 genomic EDA exon was knocked out, and the knockdown efficiency was above 70%, but the total amount of fibronectin did not change significantly. Three monoclones of EDA absent SACC- 83 cells were successfully selected with diminished migration and proliferation. The CRISPR/Cas9 system was a simplified system with relatively high knockout efficiency and EDA knockout could inhibiting SACC cell's mobility and invasiveness.

MIGRATION OF ORACLE HR DATABASE

CERN Multimedia

ais.support@cern.ch

2001-01-01

Restricted services from 3 to 7 November 2001 Due to the migration of the Oracle HR application to the Web, some services which rely on the application's availability may be disturbed from Friday 2 November at 17:30 until Thursday 8 November at 08:30. Amongst those services: HR Division: records office, recruitment, claims and benefits. FI Division: personnel accounting, advances and claims. ST Division: registration office (access cards). SPL Division: external firm staff records. EP Division: users' office. Experiments' secretariats: PIE, Greybook. Divisional secretariats: externals, internal addresses. All information concerning this migration is available at: http://ais.cern.ch We apologize for any inconvenience and thank you in advance for your understanding.

An alternative conformation of the gp41 heptad repeat 1 region coiled coil exists in the human immunodeficiency virus (HIV-1) envelope glycoprotein precursor

International Nuclear Information System (INIS)

Mische, Claudia C.; Yuan Wen; Strack, Bettina; Craig, Stewart; Farzan, Michael; Sodroski, Joseph

2005-01-01

The human immunodeficiency virus (HIV-1) transmembrane envelope glycoprotein, gp41, which mediates virus-cell fusion, exists in at least three different conformations within the trimeric envelope glycoprotein complex. The structures of the prefusogenic and intermediate states are unknown; structures representing the postfusion state have been solved. In the postfusion conformation, three helical heptad repeat 2 (HR2) regions pack in an antiparallel fashion into the hydrophobic grooves on the surface of a triple-helical coiled coil formed by the heptad repeat 1 (HR1) regions. We studied the prefusogenic conformation of gp41 by mutagenic alteration of membrane-anchored and soluble forms of the HIV-1 envelope glycoproteins. Our results indicate that, in the HIV-1 envelope glycoprotein precursor, the gp41 HR1 region is in a conformation distinct from that of a trimeric coiled coil. Thus, the central gp41 coiled coil is formed during the transition of the HIV-1 envelope glycoproteins from the precursor state to the receptor-bound intermediate

Mood and autonomic responses to repeated exposure to the Trier Social Stress Test for Groups (TSST-G).

Science.gov (United States)

Boesch, Maria; Sefidan, Sandra; Ehlert, Ulrike; Annen, Hubert; Wyss, Thomas; Steptoe, Andrew; La Marca, Roberto

2014-05-01

A group version of the Trier Social Stress Test (TSST-G) was introduced as a standardized, economic and efficient tool to induce a psychobiological stress response simultaneously in a group of subjects. The aim of the present study was to examine the efficacy of the TSST-G to repeatedly induce an affective and autonomic stress response while comparing two alternative protocols for the second examination. Healthy young male recruits participated twice in the TSST-G 10 weeks apart. In the first examination, the TSST-G consisted of a combination of mental arithmetic and a fake job interview (TSST-G-1st; n=294). For the second examination, mental arithmetic was combined with either (a) a defensive speech in response to a false shoplifting accusation (TSST-G-2nd-defence; n=105), or (b) a speech on a more neutral topic selected by the investigators (TSST-G-2nd-presentation; n=100). Affect ratings and salivary alpha-amylase (sAA) were determined immediately before and after the stress test, while heart rate (HR) and heart rate variability (HRV) were measured continuously. TSST-G-1st resulted in a significant increase of negative affect, HR, and sAA, and a significant decrease in positive affect and HRV. TSST-G-2nd, overall, resulted in a significant increase of HR and sAA (the latter only in response to TSST-G-2nd-defence) and a decrease in HRV, while no significant affect alterations were found. When comparing both, TSST-G-2nd-defence and -2nd-presentation, the former resulted in a stronger stress response with regard to HR and HRV. The findings reveal that the TSST-G is a useful protocol to repeatedly evoke an affective and autonomic stress response, while repetition leads to affective but not necessarily autonomic habituation. When interested in examining repeated psychosocial stress reactivity, a task that requires an ego-involving effort, such as a defensive speech, seems to be significantly superior to a task using an impersonal speech. Copyright © 2014 Elsevier

Hybrid Sterility in Rice (Oryza sativa L.) Involves the Tetratricopeptide Repeat Domain Containing Protein.

Science.gov (United States)

Yu, Yang; Zhao, Zhigang; Shi, Yanrong; Tian, Hua; Liu, Linglong; Bian, Xiaofeng; Xu, Yang; Zheng, Xiaoming; Gan, Lu; Shen, Yumin; Wang, Chaolong; Yu, Xiaowen; Wang, Chunming; Zhang, Xin; Guo, Xiuping; Wang, Jiulin; Ikehashi, Hiroshi; Jiang, Ling; Wan, Jianmin

2016-07-01

Intersubspecific hybrid sterility is a common form of reproductive isolation in rice (Oryza sativa L.), which significantly hampers the utilization of heterosis between indica and japonica varieties. Here, we elucidated the mechanism of S7, which specially causes Aus-japonica/indica hybrid female sterility, through cytological and genetic analysis, map-based cloning, and transformation experiments. Abnormal positioning of polar nuclei and smaller embryo sac were observed in F1 compared with male and female parents. Female gametes carrying S7(cp) and S7(i) were aborted in S7(ai)/S7(cp) and S7(ai)/S7(i), respectively, whereas they were normal in both N22 and Dular possessing a neutral allele, S7(n) S7 was fine mapped to a 139-kb region in the centromere region on chromosome 7, where the recombination was remarkably suppressed due to aggregation of retrotransposons. Among 16 putative open reading frames (ORFs) localized in the mapping region, ORF3 encoding a tetratricopeptide repeat domain containing protein was highly expressed in the pistil. Transformation experiments demonstrated that ORF3 is the candidate gene: downregulated expression of ORF3 restored spikelet fertility and eliminated absolutely preferential transmission of S7(ai) in heterozygote S7(ai)/S7(cp); sterility occurred in the transformants Cpslo17-S7(ai) Our results may provide implications for overcoming hybrid embryo sac sterility in intersubspecific hybrid rice and utilization of hybrid heterosis for cultivated rice improvement. Copyright © 2016 by the Genetics Society of America.

NEW PRECISION ORBITS OF BRIGHT DOUBLE-LINED SPECTROSCOPIC BINARIES. IV. 66 ANDROMEDAE, HR 6979, AND HR 9059

International Nuclear Information System (INIS)

Fekel, Francis C.; Williamson, Michael H.; Tomkin, Jocelyn

2010-01-01

We have determined improved spectroscopic orbits for three double-lined binaries, 66 And (F4 V), HR 6979 (Am), and HR 9059 (F5 IV) using radial velocities from the 2.1 m telescope at McDonald Observatory, the coude feed telescope at Kitt Peak National Observatory, and 2 m telescope at Fairborn Observatory. The orbital periods range from 11.0 to 14.3 days, and all three systems have eccentric orbits. The new orbital dimensions (a 1 sin i and a 2 sin i) and minimum masses (m 1 sin 3 i and m 2 sin 3 i) have accuracies of 0.2% or better. All six components of the three binary systems are rotating more slowly than their predicted pseudosynchronous rotational velocities. Hipparcos photometry of HR 9059 shows that this system has partial eclipses. Its components are nearly identical in mass and are at the very end of their main-sequence lifetimes or perhaps have just begun to traverse the Hertsprung gap.

THE IMPACT OF HR MANAGERS’ ROLES ON IMPLEMENTING BEST HR PRACTICES AND ATTRACTING AND RETAINING BEST EMPLOYEES

Directory of Open Access Journals (Sweden)

Nicoleta Valentina FLOREA

2014-10-01

Full Text Available Today’s organizations are facing new challenges, which require them to make effective decisions in order to solve complex issues. These decisions are generally made at higher levels in the organization’s hierarchical structure, where managers maintain power and control to influence organizational goals, including the behaviors and the attitudes of their subordinates. In this article we will show the importance of having effective managers, especially in HR, who can positively influence attracting intellectual capital and acquire knowledge management, by increasing employees motivation, job satisfaction, performance, and organizational commitment, in order to achieve high levels of productivity and efficiency. Also, we will evaluate the HR managers’ roles in order to obtain performance by managing, controlling, evaluating, analyzing, auditing, forecasting, and integrating effectively knowledge management and intellectual capital in organizations. Our study is made in large organizations from Dambovita County, Romania, and it demonstrates that employees need excellent HR managers to obtain the best from them and to face a changing environment.

Domain-specific and domain-general constraints on word and sequence learning.

Science.gov (United States)

Archibald, Lisa M D; Joanisse, Marc F

2013-02-01

The relative influences of language-related and memory-related constraints on the learning of novel words and sequences were examined by comparing individual differences in performance of children with and without specific deficits in either language or working memory. Children recalled lists of words in a Hebbian learning protocol in which occasional lists repeated, yielding improved recall over the course of the task on the repeated lists. The task involved presentation of pictures of common nouns followed immediately by equivalent presentations of the spoken names. The same participants also completed a paired-associate learning task involving word-picture and nonword-picture pairs. Hebbian learning was observed for all groups. Domain-general working memory constrained immediate recall, whereas language abilities impacted recall in the auditory modality only. In addition, working memory constrained paired-associate learning generally, whereas language abilities disproportionately impacted novel word learning. Overall, all of the learning tasks were highly correlated with domain-general working memory. The learning of nonwords was additionally related to general intelligence, phonological short-term memory, language abilities, and implicit learning. The results suggest that distinct associations between language- and memory-related mechanisms support learning of familiar and unfamiliar phonological forms and sequences.

Evaluation of time domain and spectral domain optical coherence tomography in the measurement of diabetic macular edema.

Science.gov (United States)

Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2008-10-01

To evaluate macular thickness and volume measurements and their intrasession repeatability in two optical coherence tomography (OCT) systems: the Stratus OCT, a time domain system, and the Cirrus HD-OCT, a spectral domain system (both by Carl Zeiss Meditec, Inc., Dublin, CA), in the context of diabetic macular edema (DME). Thirty-three eyes of 33 diabetic patients with clinically significant macular edema (CSME) were scanned in a single session by a single operator on both OCT systems. Macular thickness measurements of nine standard macular subfields and total macular volume were obtained and analyzed. Bland-Altman plots were constructed to assess agreement in macular measurements. Intraclass correlation coefficients (ICCs), coefficients of repeatability (CR(W)), and coefficients of variation (CV(W)) were used to assess intrasession repeatability. Macular thickness in nine retinal subfields and macular volume were significantly higher in the Cirrus HD-OCT system compared with the Stratus OCT system. Subfield thickness and total volume measurements, respectively, were 30 to 55 microm and 3.2 mm(3) greater for the Cirrus HD-OCT system compared with the Stratus OCT system. Both Stratus OCT and Cirrus HD-OCT systems demonstrated high intrasession repeatability, with overlapping ranges for CR(W), CV(W), and ICC. Repeatability measures (CR(W) and CV(W)) differed significantly between systems in only one of nine subfields (outer temporal subfield). Absolute measures of macular thickness and volume in patients with DME differed significantly in magnitude between the Stratus OCT and Cirrus HD-OCT systems. However, both OCT systems demonstrated high intrasessional repeatability. Although the two systems may not be used interchangeably, they appear equally reliable in generating macular measurements for clinical practice and research.

Predicting detection performance with model observers: Fourier domain or spatial domain?

Science.gov (United States)

Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

2016-02-27

The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.

Structure of filamin A immunoglobulin-like repeat 10 from Homo sapiens

International Nuclear Information System (INIS)

Page, Richard C.; Clark, Jeffrey G.; Misra, Saurav

2011-01-01

The structure of immunoglobulin-like repeat 10 from human filamin A solved at 2.44 Å resolution suggests the potential effects of mutations correlated with otopalatodigital syndrome spectrum disorders. Filamin A (FlnA) plays a critical role in cytoskeletal organization, cell motility and cellular signaling. FlnA utilizes different binding sites on a series of 24 immunoglobulin-like domains (Ig repeats) to interact with diverse cytosolic proteins and with cytoplasmic portions of membrane proteins. Mutations in a specific domain, Ig10 (FlnA-Ig10), are correlated with two severe forms of the otopalatodigital syndrome spectrum disorders Melnick–Needles syndrome and frontometaphyseal dysplasia. The crystal structure of FlnA-Ig10 determined at 2.44 Å resolution provides insight into the perturbations caused by these mutations

Daphnia HR96 is a promiscuous xenobiotic and endobiotic nuclear receptor

International Nuclear Information System (INIS)

Karimullina, Elina; Li Yangchun; Ginjupalli, Gautam K.; Baldwin, William S.

2012-01-01

Daphnia pulex is the first crustacean to have its genome sequenced. The genome project provides new insight and data into how an aquatic crustacean may respond to environmental stressors, including toxicants. We cloned Daphnia pulex HR96 (DappuHR96), a nuclear receptor orthologous to the CAR/PXR/VDR group of nuclear receptors. In Drosophila melanogaster, (hormone receptor 96) HR96 responds to phenobarbital exposure and has been hypothesized as a toxicant receptor. Therefore, we set up a transactivation assay to test whether DappuHR96 is a promiscuous receptor activated by xenobiotics and endobiotics similar to the constitutive androstane receptor (CAR) and the pregnane X-receptor (PXR). Transactivation assays performed with a GAL4-HR96 chimera demonstrate that HR96 is a promiscuous toxicant receptor activated by a diverse set of chemicals such as pesticides, hormones, and fatty acids. Several environmental toxicants activate HR96 including estradiol, pyriproxyfen, chlorpyrifos, atrazine, and methane arsonate. We also observed repression of HR96 activity by chemicals such as triclosan, androstanol, and fluoxetine. Nearly 50% of the chemicals tested activated or inhibited HR96. Interestingly, unsaturated fatty acids were common activators or inhibitors of HR96 activity, indicating a link between diet and toxicant response. The omega-6 and omega-9 unsaturated fatty acids linoleic and oleic acid activated HR96, but the omega-3 unsaturated fatty acids alpha-linolenic acid and docosahexaenoic acid inhibited HR96, suggesting that these two distinct sets of lipids perform opposing roles in Daphnia physiology. This also provides a putative mechanism by which the ratio of dietary unsaturated fats may affect the ability of an organism to respond to a toxic insult. In summary, HR96 is a promiscuous nuclear receptor activated by numerous endo- and xenobiotics.

Daphnia HR96 is a promiscuous xenobiotic and endobiotic nuclear receptor

Energy Technology Data Exchange (ETDEWEB)

Karimullina, Elina [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Institute of Plant and Animal Ecology, Russian Academy of Sciences, Ural Branch, Yekaterinburg 620144 (Russian Federation); Li Yangchun; Ginjupalli, Gautam K. [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Baldwin, William S., E-mail: baldwin@clemson.edu [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Biological Sciences, Clemson University, Clemson, SC (United States)

2012-07-15

Daphnia pulex is the first crustacean to have its genome sequenced. The genome project provides new insight and data into how an aquatic crustacean may respond to environmental stressors, including toxicants. We cloned Daphnia pulex HR96 (DappuHR96), a nuclear receptor orthologous to the CAR/PXR/VDR group of nuclear receptors. In Drosophila melanogaster, (hormone receptor 96) HR96 responds to phenobarbital exposure and has been hypothesized as a toxicant receptor. Therefore, we set up a transactivation assay to test whether DappuHR96 is a promiscuous receptor activated by xenobiotics and endobiotics similar to the constitutive androstane receptor (CAR) and the pregnane X-receptor (PXR). Transactivation assays performed with a GAL4-HR96 chimera demonstrate that HR96 is a promiscuous toxicant receptor activated by a diverse set of chemicals such as pesticides, hormones, and fatty acids. Several environmental toxicants activate HR96 including estradiol, pyriproxyfen, chlorpyrifos, atrazine, and methane arsonate. We also observed repression of HR96 activity by chemicals such as triclosan, androstanol, and fluoxetine. Nearly 50% of the chemicals tested activated or inhibited HR96. Interestingly, unsaturated fatty acids were common activators or inhibitors of HR96 activity, indicating a link between diet and toxicant response. The omega-6 and omega-9 unsaturated fatty acids linoleic and oleic acid activated HR96, but the omega-3 unsaturated fatty acids alpha-linolenic acid and docosahexaenoic acid inhibited HR96, suggesting that these two distinct sets of lipids perform opposing roles in Daphnia physiology. This also provides a putative mechanism by which the ratio of dietary unsaturated fats may affect the ability of an organism to respond to a toxic insult. In summary, HR96 is a promiscuous nuclear receptor activated by numerous endo- and xenobiotics.

The Link between HR Attributions and Employees’ Turnover Intentions

Directory of Open Access Journals (Sweden)

Juliana Caesaria Tandung

2016-02-01

Full Text Available Human Resources Management (HRM is part of the organizational functions that contribute to the effectiveness of a firm’s performance, and brings an organization a competitive advantage through the implementation of its Human Resources (HR practices. HR practices adopted by management are perceived or attributed subjectively by individual employees, and can in turn affect the employees’ attitudes and behavior (e.g. Job satisfaction and turnover intention. The purpose of this study is to contribute to the process-based approach by investigating the effect of HR attributions on turnover intentions, with job satisfaction playing a mediating role. The analysis is on the individual level, with 454 respondents from various organizations within the Netherlands. The results show that HR attributions can affect the turnover intention, through the presence of job satisfaction. Thus, it can be said that it is important to always consider the employees’ attitudes and behavior when examining their perception of HR practices, and in predicting their intention to leave.

Enrico Chiaveri: The dialogue in the HR Strategy

CERN Multimedia

2009-01-01

Enrico Chiaveri has been Head of the Human Resources Department since 2005. A core part of his department’s mission with the new Management is to develop and implement a strategic HR approach for our forward-looking Organization. He explained key aspects of the HR strategy to the Bulletin. For the first time in CERN’s history, a head of the HR Department and his deputy - Anne-Sylvie Catherin - invited the staff to a general information meeting on 23 February 2009. The scope of the meeting was to present the status of a number of current initiatives that will improve and tailor CERN’s HR strategy to the needs of the Organization and its staff, and also open up dialogue. Presented for the first time in an integrated way, the initiatives include contract policy, MARS, a staff survey, CERN’s values, a performance model, recruitment & outreach, learning & development, internal mobility and the development of a code of condu...

The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division.

Science.gov (United States)

Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S

2017-07-15

Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.

Transgenic mice display hair loss and regrowth overexpressing mutant Hr gene.

Science.gov (United States)

Zhu, Kuicheng; Xu, Cunshuan; Zhang, Jintao; Chen, Yingying; Liu, Mengduan

2017-10-30

Mutations in the hairless (Hr) gene in both mice and humans have been implicated in the development of congenital atrichia, but the role of Hr in skin and hair follicle (HF) biology remains unknown. Here, we established transgenic mice (TG) overexpressing mutant Hr to investigate its specific role in the development of HF. Three transgenic lines were successfully constructed, and two of them (TG3 and TG8) displayed a pattern of hair loss and regrowth with alternation in the expression of HR protein. The mutant Hr gene inhibited the expression of the endogenous gene in transgenic individuals, which led to the development of alopecia. Interestingly, the hair regrew with the increase in the endogenous expression levels resulting from decreased mutant Hr expression. The findings of our study indicate that the changes in the expression of Hr result in hair loss or regrowth.

The role of sexual behavior and human papillomavirus persistence in predicting repeated infections with new human papillomavirus types.

Science.gov (United States)

Moscicki, Anna-Barbara; Ma, Yifei; Jonte, Janet; Miller-Benningfield, Susanna; Hanson, Evelyn; Jay, Julie; Godwin de Medina, Cheryl; Farhat, Sepideh; Clayton, Lisa; Shiboski, Stephen

2010-08-01

Although human papillomavirus (HPV) infections are common in young women, the rate of and risk for repeated new infections are not well documented. We examined the rate of and risks for new HPV detection in young women. We used data from an ongoing study of HPV, initiated in 1990. Sexually active women ages 12 to 22 years were eligible. Interviews on behaviors and HPV testing were done at 4-month intervals; sexually transmitted infection (STI) testing was annual or if symptomatic. Starting with first HPV detection, time to the next (second) visit (event) with detection of new HPV types, and then the second event to time to third event was calculated. Risks were determined using Cox proportional hazard model. Sixty-nine percent of 1,125 women had a second event, and of those with a second event, 63% had a third event by 3 years, respectively. Women with HPV persistence from initial visit to second event [hazard ratio (HR) = 4.51 (3.78-5.37)], an STI [HR = 1.47 (1.00-2.17)], bacterial vaginosis [HR = 1.60 (1.07-2.39)], and number of new sex partners [HR = 1.10 (1.05-1.15 per partner/mo)] were independent associations for HPV. Risks for third event were similar. This study documents the repeated nature of HPV infections in young women and their association with sexual risk behaviors. This finding underscores the lack of clinical utility of HPV testing in young women. Further studies are needed to examine host factors that lead to HPV acquisition and persistence. (c)2010 AACR.

A large complement of the predicted Arabidopsis ARM repeat proteins are members of the U-box E3 ubiquitin ligase family.

Science.gov (United States)

Mudgil, Yashwanti; Shiu, Shin-Han; Stone, Sophia L; Salt, Jennifer N; Goring, Daphne R

2004-01-01

The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis.

Big domains are novel Ca²+-binding modules: evidences from big domains of Leptospira immunoglobulin-like (Lig) proteins.

Science.gov (United States)

Raman, Rajeev; Rajanikanth, V; Palaniappan, Raghavan U M; Lin, Yi-Pin; He, Hongxuan; McDonough, Sean P; Sharma, Yogendra; Chang, Yung-Fu

2010-12-29

Many bacterial surface exposed proteins mediate the host-pathogen interaction more effectively in the presence of Ca²+. Leptospiral immunoglobulin-like (Lig) proteins, LigA and LigB, are surface exposed proteins containing Bacterial immunoglobulin like (Big) domains. The function of proteins which contain Big fold is not known. Based on the possible similarities of immunoglobulin and βγ-crystallin folds, we here explore the important question whether Ca²+ binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. We selected six individual Big domains for this study (three from the conserved part of LigA and LigB, denoted as Lig A3, Lig A4, and LigBCon5; two from the variable region of LigA, i.e., 9(th) (Lig A9) and 10(th) repeats (Lig A10); and one from the variable region of LigB, i.e., LigBCen2. We have also studied the conserved region covering the three and six repeats (LigBCon1-3 and LigCon). All these proteins bind the calcium-mimic dye Stains-all. All the selected four domains bind Ca²+ with dissociation constants of 2-4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm), probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. We demonstrate that the Lig are Ca²+-binding proteins, with Big domains harbouring the binding motif. We conclude that despite differences in sequence, a Big motif binds Ca²+. This work thus sets up a strong possibility for classifying the proteins containing Big domains as a novel family of Ca²+-binding proteins. Since Big domain is a part of many proteins in bacterial kingdom, we suggest a possible function these proteins via Ca²+ binding.

Professional Development of HR Practitioners--A Phenomenographic Study

Science.gov (United States)

Bailey, Moira

2015-01-01

Purpose: The purpose of this paper is an investigation into the experiences of professional development of human resource (HR) practitioners in the North of Scotland, and the use of non-formal learning in that development. Design/methodology/approach: In-depth semi-structured interviews from a purposively selected sample of HR practitioners were…

Thermal stability of chicken brain {alpha}-spectrin repeat 17: a spectroscopic study

Energy Technology Data Exchange (ETDEWEB)

Brenner, Annette K. [University of Bergen, Department of Chemistry (Norway); Kieffer, Bruno [Ecole Superieure de Biotechnologie de Strasbourg, IGBMC Biomolecular NMR Group, CNRS UMR 7104 (France); Trave, Gilles [Ecole Superieure de Biotechnologie de Strasbourg, Equipe Oncoproteines, IREBS, UMR 7242 (France); Froystein, Nils Age [University of Bergen, Department of Chemistry (Norway); Raae, Arnt J., E-mail: arnt.raae@mbi.uib.no [University of Bergen, Department of Molecular Biology (Norway)

2012-06-15

Spectrin is a rod-like multi-modular protein that is mainly composed of triple-helical repeats. These repeats show very similar 3D-structures but variable conformational and thermodynamical stabilities, which may be of great importance for the flexibility and dynamic behaviour of spectrin in the cell. For instance, repeat 17 (R17) of the chicken brain spectrin {alpha}-chain is four times less stable than neighbouring repeat 16 (R16) in terms of Increment G. The structure of spectrin repeats has mainly been investigated by X-ray crystallography, but the structures of a few repeats, e.g. R16, have also been determined by NMR spectroscopy. Here, we undertook a detailed characterization of the neighbouring R17 by NMR spectroscopy. We assigned most backbone resonances and observed NOE restraints, relaxation values and coupling constants that all indicated that the fold of R17 is highly similar to that of R16, in agreement with previous X-ray analysis of a tandem repeat of the two domains. However, {sup 15}N heteronuclear NMR spectra measured at different temperatures revealed particular features of the R17 domain that might contribute to its lower stability. Conformational exchange appeared to alter the linker connecting R17 to R16 as well as the BC-loop in close proximity. In addition, heat-induced splitting was observed for backbone resonances of a few spatially related residues including V99 of helix C, which in R16 is replaced by the larger hydrophobic tryptophan residue that is relatively conserved among other spectrin repeats. These data support the view that the substitution of tryptophan by valine at this position may contribute to the lower stability of R17.

BTB-BACK Domain Protein POB1 Suppresses Immune Cell Death by Targeting Ubiquitin E3 ligase PUB17 for Degradation.

Directory of Open Access Journals (Sweden)

Beatriz Orosa

2017-01-01

Full Text Available Hypersensitive response programmed cell death (HR-PCD is a critical feature in plant immunity required for pathogen restriction and prevention of disease development. The precise control of this process is paramount to cell survival and an effective immune response. The discovery of new components that function to suppress HR-PCD will be instrumental in understanding the regulation of this fundamental mechanism. Here we report the identification and characterisation of a BTB domain E3 ligase protein, POB1, that functions to suppress HR-PCD triggered by evolutionarily diverse pathogens. Nicotiana benthamiana and tobacco plants with reduced POB1 activity show accelerated HR-PCD whilst those with increased POB1 levels show attenuated HR-PCD. We demonstrate that POB1 dimerization and nuclear localization are vital for its function in HR-PCD suppression. Using protein-protein interaction assays, we identify the Plant U-Box E3 ligase PUB17, a well established positive regulator of plant innate immunity, as a target for POB1-mediated proteasomal degradation. Using confocal imaging and in planta immunoprecipitation assays we show that POB1 interacts with PUB17 in the nucleus and stimulates its degradation. Mutated versions of POB1 that show reduced interaction with PUB17 fail to suppress HR-PCD, indicating that POB1-mediated degradation of PUB17 U-box E3 ligase is an important step for negative regulation of specific immune pathways in plants. Our data reveals a new mechanism for BTB domain proteins in suppressing HR-PCD in plant innate immune responses.

Poly-dipeptides encoded by the C9orf72 repeats bind nucleoli, impede RNA biogenesis, and kill cells.

Science.gov (United States)

Kwon, Ilmin; Xiang, Siheng; Kato, Masato; Wu, Leeju; Theodoropoulos, Pano; Wang, Tao; Kim, Jiwoong; Yun, Jonghyun; Xie, Yang; McKnight, Steven L

2014-09-05

Many RNA regulatory proteins controlling pre-messenger RNA splicing contain serine:arginine (SR) repeats. Here, we found that these SR domains bound hydrogel droplets composed of fibrous polymers of the low-complexity domain of heterogeneous ribonucleoprotein A2 (hnRNPA2). Hydrogel binding was reversed upon phosphorylation of the SR domain by CDC2-like kinases 1 and 2 (CLK1/2). Mutated variants of the SR domains changing serine to glycine (SR-to-GR variants) also bound to hnRNPA2 hydrogels but were not affected by CLK1/2. When expressed in mammalian cells, these variants bound nucleoli. The translation products of the sense and antisense transcripts of the expansion repeats associated with the C9orf72 gene altered in neurodegenerative disease encode GRn and PRn repeat polypeptides. Both peptides bound to hnRNPA2 hydrogels independent of CLK1/2 activity. When applied to cultured cells, both peptides entered cells, migrated to the nucleus, bound nucleoli, and poisoned RNA biogenesis, which caused cell death. Copyright © 2014, American Association for the Advancement of Science.

RING finger and WD repeat domain 3 (RFWD3) associates with replication protein A (RPA) and facilitates RPA-mediated DNA damage response.

Science.gov (United States)

Liu, Shangfeng; Chu, Jessica; Yucer, Nur; Leng, Mei; Wang, Shih-Ya; Chen, Benjamin P C; Hittelman, Walter N; Wang, Yi

2011-06-24

DNA damage response is crucial for maintaining genomic integrity and preventing cancer by coordinating the activation of checkpoints and the repair of damaged DNA. Central to DNA damage response are the two checkpoint kinases ATM and ATR that phosphorylate a wide range of substrates. RING finger and WD repeat domain 3 (RFWD3) was initially identified as a substrate of ATM/ATR from a proteomic screen. Subsequent studies showed that RFWD3 is an E3 ubiquitin ligase that ubiquitinates p53 in vitro and positively regulates p53 levels in response to DNA damage. We report here that RFWD3 associates with replication protein A (RPA), a single-stranded DNA-binding protein that plays essential roles in DNA replication, recombination, and repair. Binding of RPA to single-stranded DNA (ssDNA), which is generated by DNA damage and repair, is essential for the recruitment of DNA repair factors to damaged sites and the activation of checkpoint signaling. We show that RFWD3 is physically associated with RPA and rapidly localizes to sites of DNA damage in a RPA-dependent manner. In vitro experiments suggest that the C terminus of RFWD3, which encompass the coiled-coil domain and the WD40 domain, is necessary for binding to RPA. Furthermore, DNA damage-induced phosphorylation of RPA and RFWD3 is dependent upon each other. Consequently, loss of RFWD3 results in the persistent foci of DNA damage marker γH2AX and the repair protein Rad51 in damaged cells. These findings suggest that RFWD3 is recruited to sites of DNA damage and facilitates RPA-mediated DNA damage signaling and repair.

Repeat-associated plasticity in the Helicobacter pylori RD gene family.

Science.gov (United States)

Shak, Joshua R; Dick, Jonathan J; Meinersmann, Richard J; Perez-Perez, Guillermo I; Blaser, Martin J

2009-11-01

The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3' region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5' region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host.

Characterization of a novel gene encoding ankyrin repeat domain from Cotesia vestalis polydnavirus (CvBV)

International Nuclear Information System (INIS)

Shi Min; Chen Yafeng; Huang Fang; Liu Pengcheng; Zhou Xueping; Chen Xuexin

2008-01-01

Cotesia vestalis (Haliday) is an endoparasitoid of Plutella xylostella (L.) larvae and injects a polydnavirus (CvBV) into its host during oviposition. In this report we describe the characterization of a gene (CvBV805) and its products. CvBV805 is located on the segment S8 of CvBV genome; it has a size of 909 bp and encodes a predicted protein of 125 amino acids. This protein contains an ankyrin repeat domain with a high degree of similarity with IκB-like genes. Gene transcripts were detected in extracts of the host as early as 2 h post-parasitization (p.p.) and continued to be detected through 24 h. Tissue-specific expression patterns showed that CvBV805 might be involved in early host immunosuppression. CvBV805 was detected in parasitized hosts at 12 h p.p. and in rBac-eGFP-CvBV805-infected Tn-5B1-4 cells at 72 h.p.i. by using western blots analysis. The size of the protein expressed in the host hemocytes and infected Tn-5B1-4 cells was 17 kDa and 56 kDa (including eGFP), respectively, which nearly corresponded with the predicted molecular weight (14.31 kDa) of CvBV805, suggesting that the protein did not undergo extensive post-translational modification. The protein was confirmed to be present within the nuclear region in hemocytes of the parasitized P. xylostella larvae at 48 h p.p. using confocal laser scanning microscopy

The Jasmonate-ZIM-domain proteins interact with the WD-Repeat/bHLH/MYB complexes to regulate Jasmonate-mediated anthocyanin accumulation and trichome initiation in Arabidopsis thaliana.

Science.gov (United States)

Qi, Tiancong; Song, Susheng; Ren, Qingcuo; Wu, Dewei; Huang, Huang; Chen, Yan; Fan, Meng; Peng, Wen; Ren, Chunmei; Xie, Daoxin

2011-05-01

Jasmonates (JAs) mediate plant responses to insect attack, wounding, pathogen infection, stress, and UV damage and regulate plant fertility, anthocyanin accumulation, trichome formation, and many other plant developmental processes. Arabidopsis thaliana Jasmonate ZIM-domain (JAZ) proteins, substrates of the CORONATINE INSENSITIVE1 (COI1)-based SCF(COI1) complex, negatively regulate these plant responses. Little is known about the molecular mechanism for JA regulation of anthocyanin accumulation and trichome initiation. In this study, we revealed that JAZ proteins interact with bHLH (Transparent Testa8, Glabra3 [GL3], and Enhancer of Glabra3 [EGL3]) and R2R3 MYB transcription factors (MYB75 and Glabra1), essential components of WD-repeat/bHLH/MYB transcriptional complexes, to repress JA-regulated anthocyanin accumulation and trichome initiation. Genetic and physiological evidence showed that JA regulates WD-repeat/bHLH/MYB complex-mediated anthocyanin accumulation and trichome initiation in a COI1-dependent manner. Overexpression of the MYB transcription factor MYB75 and bHLH factors (GL3 and EGL3) restored anthocyanin accumulation and trichome initiation in the coi1 mutant, respectively. We speculate that the JA-induced degradation of JAZ proteins abolishes the interactions of JAZ proteins with bHLH and MYB factors, allowing the transcriptional function of WD-repeat/bHLH/MYB complexes, which subsequently activate respective downstream signal cascades to modulate anthocyanin accumulation and trichome initiation.

News from HR: a word from Anne-Sylvie Catherin

CERN Multimedia

2016-01-01

Anne-Sylvie Catherin, head of HR Department, looks back over her years at CERN before taking up her new position at the European Central Bank.   At the end of July, I will be leaving CERN on a special leave of absence to take up a new position at the European Central Bank. This is a new chapter in my career, in a new context with its own challenges, and as I prepare for it, I would like to take a little time to look back over my years at CERN and share with you the enriching journey it has been, both for myself and for HR. It has always been my strong belief that any organisation’s greatest asset is its people. When an HR professional believes that, it’s only a short step to the conclusion that the best way to nurture those people is by adopting a professional approach to HR. In this respect, I arrived at a very fortuitous time. Enrico Chiaveri was head of HR and, although his background is in physics, we shared that same conviction. Enrico was the icebreaker in driving change, a...

Quantitative analysis and prediction of curvature in leucine-rich repeat proteins.

Science.gov (United States)

Hindle, K Lauren; Bella, Jordi; Lovell, Simon C

2009-11-01

Leucine-rich repeat (LRR) proteins form a large and diverse family. They have a wide range of functions most of which involve the formation of protein-protein interactions. All known LRR structures form curved solenoids, although there is large variation in their curvature. It is this curvature that determines the shape and dimensions of the inner space available for ligand binding. Unfortunately, large-scale parameters such as the overall curvature of a protein domain are extremely difficult to predict. Here, we present a quantitative analysis of determinants of curvature of this family. Individual repeats typically range in length between 20 and 30 residues and have a variety of secondary structures on their convex side. The observed curvature of the LRR domains correlates poorly with the lengths of their individual repeats. We have, therefore, developed a scoring function based on the secondary structure of the convex side of the protein that allows prediction of the overall curvature with a high degree of accuracy. We also demonstrate the effectiveness of this method in selecting a suitable template for comparative modeling. We have developed an automated, quantitative protocol that can be used to predict accurately the curvature of leucine-rich repeat proteins of unknown structure from sequence alone. This protocol is available as an online resource at http://www.bioinf.manchester.ac.uk/curlrr/.

Data-driven HR how to use analytics and metrics to drive performance

CERN Document Server

Marr, Bernard

2018-01-01

Traditionally seen as a purely people function unconcerned with numbers, HR is now uniquely placed to use company data to drive performance, both of the people in the organization and the organization as a whole. Data-driven HR is a practical guide which enables HR practitioners to leverage the value of the vast amount of data available at their fingertips. Covering how to identify the most useful sources of data, how to collect information in a transparent way that is in line with data protection requirements and how to turn this data into tangible insights, this book marks a turning point for the HR profession. Covering all the key elements of HR including recruitment, employee engagement, performance management, wellbeing and training, Data-driven HR examines the ways data can contribute to organizational success by, among other things, optimizing processes, driving performance and improving HR decision making. Packed with case studies and real-life examples, this is essential reading for all HR profession...

The helicase domain of Polθ counteracts RPA to promote alt-NHEJ.

Science.gov (United States)

Mateos-Gomez, Pedro A; Kent, Tatiana; Deng, Sarah K; McDevitt, Shane; Kashkina, Ekaterina; Hoang, Trung M; Pomerantz, Richard T; Sfeir, Agnel

2017-12-01

Mammalian polymerase theta (Polθ) is a multifunctional enzyme that promotes error-prone DNA repair by alternative nonhomologous end joining (alt-NHEJ). Here we present structure-function analyses that reveal that, in addition to the polymerase domain, Polθ-helicase activity plays a central role during double-strand break (DSB) repair. Our results show that the helicase domain promotes chromosomal translocations by alt-NHEJ in mouse embryonic stem cells and also suppresses CRISPR-Cas9- mediated gene targeting by homologous recombination (HR). In vitro assays demonstrate that Polθ-helicase activity facilitates the removal of RPA from resected DSBs to allow their annealing and subsequent joining by alt-NHEJ. Consistent with an antagonistic role for RPA during alt-NHEJ, inhibition of RPA1 enhances end joining and suppresses recombination. Taken together, our results reveal that the balance between HR and alt-NHEJ is controlled by opposing activities of Polθ and RPA, providing further insight into the regulation of repair-pathway choice in mammalian cells.

Structure and biochemical function of a prototypical Arabidopsis U-box domain

DEFF Research Database (Denmark)

Andersen, Pernille; Kragelund, Birthe B; Olsen, Addie N

2004-01-01

U-box proteins, as well as other proteins involved in regulated protein degradation, are apparently over-represented in Arabidopsis compared with other model eukaryotes. The Arabidopsis protein AtPUB14 contains a typical U-box domain followed by an Armadillo repeat region, a domain organization t...

A Large Complement of the Predicted Arabidopsis ARM Repeat Proteins Are Members of the U-Box E3 Ubiquitin Ligase Family1[w

Science.gov (United States)

Mudgil, Yashwanti; Shiu, Shin-Han; Stone, Sophia L.; Salt, Jennifer N.; Goring, Daphne R.

2004-01-01

The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis. PMID:14657406

Managing (Sales)People towards Performance: HR Strategy, Leadership & Teamwork

NARCIS (Netherlands)

H.M.S. Dietz (Bart)

2009-01-01

textabstractManaging people towards performance is one of the most critical priorities for managers in practice. This dissertation focuses on this important issue and explores how HR Strategy, Leaders, and Teams, impact performance. It addresses respectively how HR as a system of coherent

The Factors of Forming the National HR-Management Model

Directory of Open Access Journals (Sweden)

Elena P. Kostenko

2017-12-01

Full Text Available There are some factors considered in this article, which influence the forming of national HR-management model. The group-forming criterion is the nature of factors, that determine the system of HR-management as a system of corporate culture values, norms and rules of organizational behavior, ways of realization some important managing functions and dominating approaches to make decisions. This article shows that the plurality of combinations in different factors leads to forming the unique HR-management model. The geoclimatic factor influences the principles of the labor organization (orientation primarily on individual or collective forms of labor, attitude to the management experience of other countries, attitude to resources, etc., the distribution of labor resources, the level of labor mobility, and the psychosocial type of employee. Models of man's labor behavior are constituted In the process of historical development. Attention is focused on the formation of a national HR-model, such as the conducted socio-economic policy, the characteristics of the institutional environment, economic goals and priorities of the country's development, the level of development and the nature of the national productive forces and economic structures. Much attention was paid to the analysis of the historically formed value system and labor traditions, which influence the approaches to HR-management. As far as religion influences the model of person’s inclusion in labor, motives of labor behavior, management culture of a certain employee, preferred payment etc., we examined how the main traditional religions (Christianity, Islam, Judaism, Buddhism, Confucianism, Hinduism influence the HR-management system in different countries.

Big domains are novel Ca²+-binding modules: evidences from big domains of Leptospira immunoglobulin-like (Lig proteins.

Directory of Open Access Journals (Sweden)

Rajeev Raman

Full Text Available BACKGROUND: Many bacterial surface exposed proteins mediate the host-pathogen interaction more effectively in the presence of Ca²+. Leptospiral immunoglobulin-like (Lig proteins, LigA and LigB, are surface exposed proteins containing Bacterial immunoglobulin like (Big domains. The function of proteins which contain Big fold is not known. Based on the possible similarities of immunoglobulin and βγ-crystallin folds, we here explore the important question whether Ca²+ binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. PRINCIPAL FINDINGS: We selected six individual Big domains for this study (three from the conserved part of LigA and LigB, denoted as Lig A3, Lig A4, and LigBCon5; two from the variable region of LigA, i.e., 9(th (Lig A9 and 10(th repeats (Lig A10; and one from the variable region of LigB, i.e., LigBCen2. We have also studied the conserved region covering the three and six repeats (LigBCon1-3 and LigCon. All these proteins bind the calcium-mimic dye Stains-all. All the selected four domains bind Ca²+ with dissociation constants of 2-4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm, probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. CONCLUSIONS: We demonstrate that the Lig are Ca²+-binding proteins, with Big domains harbouring the binding motif. We conclude that despite differences in sequence, a Big motif binds Ca²+. This work thus sets up a strong possibility for classifying the proteins containing Big domains as a novel family of Ca²+-binding proteins. Since Big domain is a part of many proteins in bacterial kingdom, we suggest a possible function these proteins via Ca²+ binding.

Single molecule study of the intrinsically disordered FG-repeat nucleoporin 153.

Science.gov (United States)

Milles, Sigrid; Lemke, Edward A

2011-10-05

Nucleoporins (Nups), which are intrinsically disordered, form a selectivity filter inside the nuclear pore complex, taking a central role in the vital nucleocytoplasmic transport mechanism. These Nups display a complex and nonrandom amino-acid architecture of phenylalanine glycine (FG)-repeat clusters and intra-FG linkers. How such heterogeneous sequence composition relates to function and could give rise to a transport mechanism is still unclear. Here we describe a combined chemical biology and single-molecule fluorescence approach to study the large human Nup153 FG-domain. In order to obtain insights into the properties of this domain beyond the average behavior, we probed the end-to-end distance (R(E)) of several ∼50-residues long FG-repeat clusters in the context of the whole protein domain. Despite the sequence heterogeneity of these FG-clusters, we detected a reoccurring and consistent compaction from a relaxed coil behavior under denaturing conditions (R(E)/R(E,RC) = 0.99 ± 0.15 with R(E,RC) corresponding to ideal relaxed coil behavior) to a collapsed state under native conditions (R(E)/R(E,RC) = 0.79 ± 0.09). We then analyzed the properties of this protein on the supramolecular level, and determined that this human FG-domain was in fact able to form a hydrogel with physiological permeability barrier properties. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Domain movement within a gene: a novel evolutionary mechanism for protein diversification.

Directory of Open Access Journals (Sweden)

Yoshikazu Furuta

Full Text Available A protein function is carried out by a specific domain localized at a specific position. In the present study, we report that, within a gene, a specific amino acid sequence can move between a certain position and another position. This was discovered when the sequences of restriction-modification systems within the bacterial species Helicobacter pylori were compared. In the specificity subunit of Type I restriction-modification systems, DNA sequence recognition is mediated by target recognition domain 1 (TRD1 and TRD2. To our surprise, several sequences are shared by TRD1 and TRD2 of genes (alleles at the same locus (chromosomal location; these domains appear to have moved between the two positions. The gene/protein organization can be represented as x-(TRD1-y-x-(TRD2-y, where x and y represent repeat sequences. Movement probably occurs by recombination at these flanking DNA repeats. In accordance with this hypothesis, recombination at these repeats also appears to decrease two TRDs into one TRD or increase these two TRDs to three TRDs (TRD1-TRD2-TRD2 and to allow TRD movement between genes even at different loci. Similar movement of domains between TRD1 and TRD2 was observed for the specificity subunit of a Type IIG restriction enzyme. Similar movement of domain between TRD1 and TRD2 was observed for Type I restriction-modification enzyme specificity genes in two more eubacterial species, Streptococcus pyogenes and Mycoplasma agalactiae. Lateral domain movements within a protein, which we have designated DOMO (domain movement, represent novel routes for the diversification of proteins.

Solution properties of the archaeal CRISPR DNA repeat-binding homeodomain protein Cbp2

DEFF Research Database (Denmark)

Kenchappa, Chandra; Heiðarsson, Pétur Orri; Kragelund, Birthe

2013-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) form the basis of diverse adaptive immune systems directed primarily against invading genetic elements of archaea and bacteria. Cbp1 of the crenarchaeal thermoacidophilic order Sulfolobales, carrying three imperfect repeats, binds...... specifically to CRISPR DNA repeats and has been implicated in facilitating production of long transcripts from CRISPR loci. Here, a second related class of CRISPR DNA repeat-binding protein, denoted Cbp2, is characterized that contains two imperfect repeats and is found amongst members of the crenarchaeal...... in facilitating high affinity DNA binding of Cbp2 by tethering the two domains. Structural studies on mutant proteins provide support for Cys(7) and Cys(28) enhancing high thermal stability of Cbp2(Hb) through disulphide bridge formation. Consistent with their proposed CRISPR transcriptional regulatory role, Cbp2...

Conformational analysis of isolated domains of Helicobacter pylori CagA.

Directory of Open Access Journals (Sweden)

Amanda P Woon

Full Text Available The CagA protein of Helicobacter pylori is associated with increased virulence and gastric cancer risk. CagA is translocated into the host cell by a H. pylori type IV secretion system via mechanisms that are poorly understood. Translocated CagA interacts with numerous host factors, altering a variety of host signalling pathways. The recently determined crystal structure of C-terminally-truncated CagA indicated the presence of two domains: the smaller, flexible N-terminal domain and the larger, middle domain. In this study, we have investigated the conformation, oligomeric state and stability of the N-terminal, middle and glutamate-proline-isoleucine-tyrosine-alanine (EPIYA-repeats domains. All three domains are monomeric, suggesting that the multimerisation of CagA observed in infected cells is likely to be mediated not by CagA itself but by its interacting partners. The middle and the C-terminal domains, but not the N-terminal domain, are capable of refolding spontaneously upon heat denaturation, lending support to the hypothesis that unfolded CagA is threaded C-terminus first through the type IV secretion channel with its N-terminal domain, which likely requires interactions with other domains to refold, being threaded last. Our findings also revealed that the C-terminal EPIYA-repeats domain of CagA exists in an intrinsically disordered premolten globule state with regions in PPII conformation--a feature that is shared by many scaffold proteins that bind multiple protein components of signalling pathways. Taken together, these results provide a deeper understanding of the physicochemical properties of CagA that underpin its complex cellular and oncogenic functions.

The number of genes encoding repeat domain-containing proteins positively correlates with genome size in amoebal giant viruses

Science.gov (United States)

Shukla, Avi; Chatterjee, Anirvan

2018-01-01

Abstract Curiously, in viruses, the virion volume appears to be predominantly driven by genome length rather than the number of proteins it encodes or geometric constraints. With their large genome and giant particle size, amoebal viruses (AVs) are ideally suited to study the relationship between genome and virion size and explore the role of genome plasticity in their evolutionary success. Different genomic regions of AVs exhibit distinct genealogies. Although the vertically transferred core genes and their functions are universally conserved across the nucleocytoplasmic large DNA virus (NCLDV) families and are essential for their replication, the horizontally acquired genes are variable across families and are lineage-specific. When compared with other giant virus families, we observed a near–linear increase in the number of genes encoding repeat domain-containing proteins (RDCPs) with the increase in the genome size of AVs. From what is known about the functions of RDCPs in bacteria and eukaryotes and their prevalence in the AV genomes, we envisage important roles for RDCPs in the life cycle of AVs, their genome expansion, and plasticity. This observation also supports the evolution of AVs from a smaller viral ancestor by the acquisition of diverse gene families from the environment including RDCPs that might have helped in host adaption. PMID:29308275

Repeat-Associated Plasticity in the Helicobacter pylori RD Gene Family▿ †

Science.gov (United States)

Shak, Joshua R.; Dick, Jonathan J.; Meinersmann, Richard J.; Perez-Perez, Guillermo I.; Blaser, Martin J.

2009-01-01

The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3′ region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5′ region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host. PMID:19749042

Molecular Mechanics of the α-Actinin Rod Domain: Bending, Torsional, and Extensional Behavior

Science.gov (United States)

Golji, Javad; Collins, Robert; Mofrad, Mohammad R. K.

2009-01-01

α-Actinin is an actin crosslinking molecule that can serve as a scaffold and maintain dynamic actin filament networks. As a crosslinker in the stressed cytoskeleton, α-actinin can retain conformation, function, and strength. α-Actinin has an actin binding domain and a calmodulin homology domain separated by a long rod domain. Using molecular dynamics and normal mode analysis, we suggest that the α-actinin rod domain has flexible terminal regions which can twist and extend under mechanical stress, yet has a highly rigid interior region stabilized by aromatic packing within each spectrin repeat, by electrostatic interactions between the spectrin repeats, and by strong salt bridges between its two anti-parallel monomers. By exploring the natural vibrations of the α-actinin rod domain and by conducting bending molecular dynamics simulations we also predict that bending of the rod domain is possible with minimal force. We introduce computational methods for analyzing the torsional strain of molecules using rotating constraints. Molecular dynamics extension of the α-actinin rod is also performed, demonstrating transduction of the unfolding forces across salt bridges to the associated monomer of the α-actinin rod domain. PMID:19436721

Outsourcing HR Services: The Role of Human Resource Intermediaries

Science.gov (United States)

Kock, Henrik; Wallo, Andreas; Nilsson, Barbro; Hoglund, Cecilia

2012-01-01

Purpose: In this article, the area of interest is an emerging type of organisation called human resource intermediaries (HRIs), which focus on delivering human resource (HR) services to public sector organisations and private companies. The purpose of this article is, thus, to explore HRIs as deliverers of HR services. More specifically, the…

African American Accounting Majors and the 150-hr Requirement

Science.gov (United States)

Booker, Quinton; Hill, Cecil L.; Wright, Carl

2010-01-01

The study provides information on African American accounting majors' views regarding 150-hr issues. The authors collected data from 152 students at two schools. Students at one school supported the requirement while those at the other school did not. However, students believed that the 150-hr requirement enhances the quality of certified public…

Enabling quaternion derivatives: the generalized HR calculus

Science.gov (United States)

Xu, Dongpo; Jahanchahi, Cyrus; Took, Clive C.; Mandic, Danilo P.

2015-01-01

Quaternion derivatives exist only for a very restricted class of analytic (regular) functions; however, in many applications, functions of interest are real-valued and hence not analytic, a typical case being the standard real mean square error objective function. The recent HR calculus is a step forward and provides a way to calculate derivatives and gradients of both analytic and non-analytic functions of quaternion variables; however, the HR calculus can become cumbersome in complex optimization problems due to the lack of rigorous product and chain rules, a consequence of the non-commutativity of quaternion algebra. To address this issue, we introduce the generalized HR (GHR) derivatives which employ quaternion rotations in a general orthogonal system and provide the left- and right-hand versions of the quaternion derivative of general functions. The GHR calculus also solves the long-standing problems of product and chain rules, mean-value theorem and Taylor's theorem in the quaternion field. At the core of the proposed GHR calculus is quaternion rotation, which makes it possible to extend the principle to other functional calculi in non-commutative settings. Examples in statistical learning theory and adaptive signal processing support the analysis. PMID:26361555

Comparative study of a novel application of automated HR HPV assay and stability in a previously untested Preservative media

Directory of Open Access Journals (Sweden)

Mike E. Morel

2017-12-01

Full Text Available Background: The suitability and stability of cervical cells in Novaprep media (NHQ for certain HPV assays is unknown. Methods: We evaluated the accuracy of an automated HPV assay (Abbott RealTime HR HPV for cervical cells prepared in NHQ and NHQ with a pre-treatment to mimic a worst case clinical use, compared to the assay manufacturers media; repeatability and reproducibility of HPV results and the stability of detectable HPV in NHQ over time compared to CE marked liquid based cytology preservatives. Cell lines were used to simulate patient samples. Results: Cells stored in NHQ produced accurate, repeatable and reproducible results. Stability in NHQ was comparable to the best performing LBC, with at least 7 months’ stability at 18–25 °C, 2–8 °C, −20 °C and −80 °C; and at least 3 months’ stability at 40 °C. Similar results were obtained for pre-treated NHQ except only 3.5 months’ stability at 18–25 °C. Cell line samples in all media and concentrations tested were detected appropriately by the assay. Conclusions: Based on this first stage validation analytical study, cervical cells stored in NHQ are suitable for the Realtime HPV assay. There should be no reservations for inclusion of NHQ in any further validation and clinical performance evaluation of this assay. Keywords: HPV, Preservative, Sample stability, Automated HR HPV assay

History, rare, and multiple events of mechanical unfolding of repeat proteins

Science.gov (United States)

Sumbul, Fidan; Marchesi, Arin; Rico, Felix

2018-03-01

Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.

Preservice science teachers' experiences with repeated, guided inquiry

Science.gov (United States)

Slack, Amy B.

The purpose of this study was to examine preservice science teachers' experiences with repeated scientific inquiry (SI) activities. The National Science Education Standards (National Research Council, 1996) stress students should understand and possess the abilities to do SI. For students to meet these standards, science teachers must understand and be able to perform SI; however, previous research demonstrated that many teachers have naive understandings in this area. Teacher preparation programs provide an opportunity to facilitate the development of inquiry understandings and abilities. In this study, preservice science teachers had experiences with two inquiry activities that were repeated three times each. The research questions for this study were (a) How do preservice science teachers' describe their experiences with repeated, guided inquiry activities? (b) What are preservice science teachers' understandings and abilities of SI? This study was conducted at a large, urban university in the southeastern United States. The 5 participants had bachelor's degrees in science and were enrolled in a graduate science education methods course. The researcher was one of the course instructors but did not lead the activities. Case study methodology was used. Data was collected from a demographic survey, an open-ended questionnaire with follow-up interviews, the researcher's observations, participants' lab notes, personal interviews, and participants' journals. Data were coded and analyzed through chronological data matrices to identify patterns in participants' experiences. The five domains identified in this study were understandings of SI, abilities to conduct SI, personal feelings about the experience, science content knowledge, and classroom implications. Through analysis of themes identified within each domain, the four conclusions made about these preservice teachers' experiences with SI were that the experience increased their abilities to conduct inquiry

CROATIAN ADULT SPOKEN LANGUAGE CORPUS (HrAL

Directory of Open Access Journals (Sweden)

Jelena Kuvač Kraljević

2016-01-01

Full Text Available Interest in spoken-language corpora has increased over the past two decades leading to the development of new corpora and the discovery of new facets of spoken language. These types of corpora represent the most comprehensive data source about the language of ordinary speakers. Such corpora are based on spontaneous, unscripted speech defined by a variety of styles, registers and dialects. The aim of this paper is to present the Croatian Adult Spoken Language Corpus (HrAL, its structure and its possible applications in different linguistic subfields. HrAL was built by sampling spontaneous conversations among 617 speakers from all Croatian counties, and it comprises more than 250,000 tokens and more than 100,000 types. Data were collected during three time slots: from 2010 to 2012, from 2014 to 2015 and during 2016. HrAL is today available within TalkBank, a large database of spoken-language corpora covering different languages (https://talkbank.org, in the Conversational Analyses corpora within the subsection titled Conversational Banks. Data were transcribed, coded and segmented using the transcription format Codes for Human Analysis of Transcripts (CHAT and the Computerised Language Analysis (CLAN suite of programmes within the TalkBank toolkit. Speech streams were segmented into communication units (C-units based on syntactic criteria. Most transcripts were linked to their source audios. The TalkBank is public free, i.e. all data stored in it can be shared by the wider community in accordance with the basic rules of the TalkBank. HrAL provides information about spoken grammar and lexicon, discourse skills, error production and productivity in general. It may be useful for sociolinguistic research and studies of synchronic language changes in Croatian.

The phosphoCTD-interacting domain of Topoisomerase I

International Nuclear Information System (INIS)

Wu, Jianhong; Phatnani, Hemali P.; Hsieh, Tao-Shih; Greenleaf, Arno L.

2010-01-01

The N-terminal domain (NTD) of Drosophila melanogaster (Dm) Topoisomerase I has been shown to bind to RNA polymerase II, but the domain of RNAPII with which it interacts is not known. Using bacterially-expressed fusion proteins carrying all or half of the NTDs of Dm and human (Homo sapiens, Hs) Topo I, we demonstrate that the N-terminal half of each NTD binds directly to the hyperphosphorylated C-terminal repeat domain (phosphoCTD) of the largest RNAPII subunit, Rpb1. Thus, the amino terminal segment of metazoan Topo I (1-157 for Dm and 1-114 for Hs) contains a novel phosphoCTD-interacting domain that we designate the Topo I-Rpb1 interacting (TRI) domain. The long-known in vivo association of Topo I with active genes presumably can be attributed, wholly or in part, to the TRI domain-mediated binding of Topo I to the phosphoCTD of transcribing RNAPII.

The phosphoCTD-interacting domain of Topoisomerase I

Energy Technology Data Exchange (ETDEWEB)

Wu, Jianhong; Phatnani, Hemali P.; Hsieh, Tao-Shih [Department of Biochemistry, Duke University Medical Center, Durham, NC 27710 (United States); Greenleaf, Arno L., E-mail: arno.greenleaf@duke.edu [Department of Biochemistry, Duke University Medical Center, Durham, NC 27710 (United States)

2010-06-18

The N-terminal domain (NTD) of Drosophila melanogaster (Dm) Topoisomerase I has been shown to bind to RNA polymerase II, but the domain of RNAPII with which it interacts is not known. Using bacterially-expressed fusion proteins carrying all or half of the NTDs of Dm and human (Homo sapiens, Hs) Topo I, we demonstrate that the N-terminal half of each NTD binds directly to the hyperphosphorylated C-terminal repeat domain (phosphoCTD) of the largest RNAPII subunit, Rpb1. Thus, the amino terminal segment of metazoan Topo I (1-157 for Dm and 1-114 for Hs) contains a novel phosphoCTD-interacting domain that we designate the Topo I-Rpb1 interacting (TRI) domain. The long-known in vivo association of Topo I with active genes presumably can be attributed, wholly or in part, to the TRI domain-mediated binding of Topo I to the phosphoCTD of transcribing RNAPII.

Repeatability of metabolic responses to a nutrient deficiency in early and mid lactation and implications for robustness of dairy cows.

Science.gov (United States)

Gross, J J; Bruckmaier, R M

2015-12-01

Nutrient partitioning toward the mammary gland during insufficient energy and nutrient supply is a strategy to ensure survival of the offspring in mammalian species. This homeorhetic priority of the mammary gland is also present in the modern dairy cow, in particular in early lactation. However, despite similar metabolic loads, the adaptive response to a given metabolic load varies considerably among animals. The aim of this study was to investigate if individual cows respond in a consistent manner to a negative energy balance (NEB) in early and mid lactation. Twenty-five dairy cows experienced the usual NEB after parturition and were subjected to a second 3-wk NEB induced by feed restriction in mid lactation. Animals were retrospectively ranked according to their highest plasma nonesterified fatty acid (NEFA) concentration in wk 1 to 4 postpartum. The animals with the 33% highest and 33% lowest values were selected and classified either as the high response (HR) or low response (LR) group. Before parturition, no differences in the studied parameters, dry matter intake, energy balance, concentrations of glucose, NEFA, β-hydroxybutyrate, cholesterol, triglycerides, growth hormone, and insulin-like growth factor-1, were detected between LR and HR. After parturition, milk yield and energy-corrected milk yield was higher for HR compared with LR in wk 2 to 14 and wk 1 to 6, respectively. During feed restriction in wk 15 to 17 postpartum, no differences in energy-corrected milk between LR and HR were found. Energy balance was more negative in HR during the NEB in early lactation, but not different from LR during feed restriction in mid lactation. Although plasma concentrations of glucose, growth hormone, triglycerides, and cholesterol showed group differences in early lactation, but not during feed restriction, the plasma concentrations of NEFA, β-hydroxybutyrate, and insulin-like growth factor-1 in HR changed repeatedly to a greater extent during the NEB at the 2

Deletion of Repeats in the Alpha C Protein Enhances the Pathogenicity of Group B Streptococci in Immune Mice

OpenAIRE

Gravekamp, C.; Rosner, Bernard; Madoff, L. C.

1998-01-01

The alpha C protein is a protective surface-associated antigen of group B streptococci (GBS). The prototype alpha C protein of GBS (strain A909) contains nine identical tandem repeats, each comprising 82 amino acids, flanked by N- and C-terminal domains. Clinical isolates of GBS show variable numbers of repeats with a normal distribution and a median of 9 to 10 repeats. Here, we show that escape mutants of GBS expressing one-repeat alpha C protein were 100-fold more pathogenic than GBS expres...

Value creation through HR shared services: towards a conceptual framework

NARCIS (Netherlands)

Meijerink, Jeroen Gerard; Bondarouk, Tatiana; Looise, Jan C.

2013-01-01

Purpose – The purpose of this paper is to derive a measure for the performance of human resource shared service providers (HR SSPs) and then to develop a theoretical framework that conceptualises their performance. Design/methodology/approach – This conceptual paper starts from the HR shared

CERN HR receives award for on-line recruitment and communication

CERN Multimedia

Joannah Caborn Wengler

2012-01-01

In a survey of 21,000 European students, CERN ranked 15th, ahead of giants like Microsoft and Nestlé, for the quality of its on-line "talent communication", that is how it uses the Internet to attract job applicants. HR now boasts a new virtual award, certifying its on-line savvy.   The "virtual" award given to HR. How did you get your job at CERN? Via the CERN HR website, or Facebook, or Twitter? Or were you headhunted on LinkedIn? Particularly if you’re from the younger generation, chances are that you used some form of on-line recruitment. In this case you will have used one of the best recruitment tools in Europe, according to the 2012 OTaC (Online Talent Communication) study, carried out by a research institute named Potentialpark. It surveyed over 21,000 students, asking them to rate employers’ use of seven different channels of communication about jobs and careers, from HR websites and on-line application systems to the...

PLEIADES-HR IMAGE QUALITY COMMISSIONING

Directory of Open Access Journals (Sweden)

L. Lebègue

2012-07-01

Full Text Available PLEIADES is the highest resolution civilian earth observing system ever developed in Europe. This imagery program is conducted by the French National Space Agency, CNES. It operates since 2012 a first satellite PLEIADES-HR launched on 2011 December 17th, a second one should be launched by the end of the year. Each satellite is designed to provide optical 70 cm resolution coloured images to civilian and defence users. The Image Quality requirements were defined from users studies from the different spatial imaging applications, taking into account the trade-off between on-board technological complexity and ground processing capacity. The assessment of the image quality and the calibration operation have been performed by CNES Image Quality team during the 6 month commissioning phase that followed the satellite launch. These activities cover many topics gathered in two families : radiometric and geometric image quality. The new capabilities offered by PLEIADES-HR agility allowed to imagine new methods of image calibration and performance assessment. Starting from an overview of the satellite characteristics, this paper presents all the calibration operations that were conducted during the commissioning phase and also gives the main results for every image quality performance.

Characterisation and evaluation of antiviral recombinant peptides based on the heptad repeat regions of NDV and IBV fusion glycoproteins

International Nuclear Information System (INIS)

Wang Xiaojia; Li Chuangen; Chi Xiaojing; Wang Ming

2011-01-01

Mixed virus infections can cause livestock losses that are more devastating than those caused by single virus infections. Newcastle disease virus (NDV) and infectious bronchitis virus (IBV), serious threats to the poultry industry, can give rise to complex mixed infections that hinder diagnosis and prevention. In this study, we show that newly designed peptides, which are based on the heptad repeat (HR) region of the fusion glycoproteins from NDV and IBV, have more potent antiviral activity than the mother HR peptides. Plaque formation and chicken embryo infectivity assays confirmed these results. The novel peptides completely inhibited single virus infections and mixed infections caused by NDV and IBV. Furthermore, we assessed cell toxicity and possible targets for the peptides, thereby strengthening the notion that HR2 is an attractive site for therapeutic intervention. These results suggest the possibility of designing a relatively broad-spectrum class of antiviral peptides that can reduce the effects of mixed-infections.

Domain structures and magnetization reversal in Co/Pd and CoFeB/Pd multilayers

Energy Technology Data Exchange (ETDEWEB)

Sbiaa, R., E-mail: rachid@squ.edu.om [Department of Physics, Sultan Qaboos University, P.O. Box 36, PC 123 (Oman); Ranjbar, M. [Physics Department, University of Gothenburg, 412 96 Gothenburg (Sweden); Åkerman, J. [Physics Department, University of Gothenburg, 412 96 Gothenburg (Sweden); Materials Physics, School of ICT, Royal Institute of Technology (KTH), 164 40 Kista (Sweden)

2015-05-07

Domain structures and magnetization reversal of (Co/Pd) and (CoFeB/Pd) multilayers with 7 and 14 repeats were investigated. The Co-based multilayers show much larger coercivities, a better squareness, and a sharper magnetization switching than CoFeB-based multilayers. From magnetic force microscopy observations, both structures show strong reduction in domains size as the number of repeats increases but the magnetic domains for Co-based multilayers are more than one order of magnitude larger than for CoFeB-based multilayers. By imaging domains at different times, breaks in the (CoFeB/Pd) multilayer stripes were observed within only few hours, while no change could be seen for (Co/Pd) multilayers. Although CoFeB single layers are suitable for magnetoresistive devices due to their large spin polarization and low damping constants, their lamination with Pd suffers mainly from thermal instability.

Composite Spectra Paper 1: HR 6902

Indian Academy of Sciences (India)

tribpo

spectra; in many cases we have used the maximum width permitted by the optics of ... 10 mЕ, corresponding to 1 µm the plate, are the norm. ..... an inequality ..... on the spectra of HR 6902, we have thought it appropriate to weight the four ...

Why a well-designed HR shared service provider fails to create end-user value?

NARCIS (Netherlands)

Meijerink, Jeroen Gerard; Bondarouk, Tatiana; Looise, Jan C.

2011-01-01

Human resource shared services centres (HR SSCs) are foreseen as improving HR service delivery for their end-users: employees, line managers and decentralized HR professionals. Although the concept expects the benefits of HR SSCs to come from centralizing knowledge and decentralizing the control

Functional and topological characteristics of mammalian regulatory domains

Science.gov (United States)

Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

2014-01-01

Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

Crystal structure of the second fibronectin type III (FN3) domain from human collagen α1 type XX.

Science.gov (United States)

Zhao, Jingfeng; Ren, Jixia; Wang, Nan; Cheng, Zhong; Yang, Runmei; Lin, Gen; Guo, Yi; Cai, Dayong; Xie, Yong; Zhao, Xiaohong

2017-12-01

Collagen α1 type XX, which contains fibronectin type III (FN3) repeats involving six FN3 domains (referred to as the FN#1-FN#6 domains), is an unusual member of the fibril-associated collagens with interrupted triple helices (FACIT) subfamily of collagens. The results of standard protein BLAST suggest that the FN3 repeats might contribute to collagen α1 type XX acting as a cytokine receptor. To date, solution NMR structures of the FN#3, FN#4 and FN#6 domains have been determined. To obtain further structural evidence to understand the relationship between the structure and function of the FN3 repeats from collagen α1 type XX, the crystal structure of the FN#2 domain from human collagen α1 type XX (residues Pro386-Pro466; referred to as FN2-HCXX) was solved at 2.5 Å resolution. The crystal structure of FN2-HCXX shows an immunoglobulin-like fold containing a β-sandwich structure, which is formed by a three-stranded β-sheet (β1, β2 and β5) packed onto a four-stranded β-sheet (β3, β4, β6 and β7). Two consensus domains, tencon and fibcon, are structural analogues of FN2-HCXX. Fn8, an FN3 domain from human oncofoetal fibronectin, is the closest structural analogue of FN2-HCXX derived from a naturally occurring sequence. Based solely on the structural similarity of FN2-HCXX to other FN3 domains, the detailed functions of FN2-HCXX and the FN3 repeats in collagen α1 type XX cannot be identified.

Crystal structure of a PFU-PUL domain pair of Saccharomyces cerevisiae Doa1/Ufd3.

Science.gov (United States)

Nishimasu, Rieko; Komori, Hirofumi; Higuchi, Yoshiki; Nishimasu, Hiroshi; Hiroaki, Hidekazu

2010-10-21

Doa1/Ufd3 is involved in ubiquitin (Ub)-dependent cellular processes in Saccharomyces cerevisiae, and consists of WD40, PFU, and PUL domains. Previous studies showed that the PFU and PUL domains interact with Ub and Hse1, and Cdc48, respectively. However, their detailed functional interactions with Doa1 remained elusive. We report the crystal structure of the PFU-PUL domain pair of yeast Doa1 at 1.9 Å resolution. The conserved surface of the PFU domain may be involved in binding to Ub and Hse1. Unexpectedly, the PUL domain consists of an Armadillo (ARM)-like repeat structure. The positively charged concave surface of the PUL domain may bind to the negatively charged C-terminal region of Cdc48. A structural comparison of Doa1 with Ufd2 revealed that they share a similar ARM-like repeat, supporting a model in which Doa1 and Ufd2 compete for Cdc48 binding and may dictate the fate of ubiquitinated proteins in the proteasome pathway.

Validation of calcaneus trabecular microstructure measurements by HR-pQCT.

Science.gov (United States)

Metcalf, Louis M; Dall'Ara, Enrico; Paggiosi, Margaret A; Rochester, John R; Vilayphiou, Nicolas; Kemp, Graham J; McCloskey, Eugene V

2018-01-01

Assessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against 'gold-standard' micro-CT measurements. Ten human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82μm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Dissected portions of these bones were scanned using micro-computed tomography (micro-CT) at an isotropic 17.4μm voxel size. HR-pQCT images were rigidly registered to those obtained with micro-CT and divided into multiple 5mm sided cubes to evaluate and compare morphometric parameters between the modalities. Standard HR-pQCT measurements (derived bone volume fraction (BV/TV d ); trabecular number, Tb.N; derived trabecular thickness, Tb.Th d ; derived trabecular spacing, Tb.Sp d ) and corresponding micro-CT voxel-based measurements (BV/TV, Tb.N, Tb.Th, Tb.Sp) were compared. A total of 108 regions of interest were analysed across the 10 specimens. At all integration times HR-pQCT BV/TV d was strongly correlated with micro-CT BV/TV (r 2 =0.95-0.98, RMSE=1%), but BV/TV d was systematically lower than that measured by micro-CT (mean bias=5%). In contrast, HR-pQCT systematically overestimated Tb.N at all integration times; of the in situ scans, 200ms yielded the lowest mean bias and the strongest correlation with micro-CT (r 2 =0.61, RMSE=0.15mm -1 ). Regional analysis revealed greater accuracy for Tb.N in the superior regions of the calcaneus at all integration times in situ (mean bias=0.44-0.85mm -1 ; r 2 =0.70-0.88, pmicrostructure, particularly in the superior region of the calcaneus, can be assessed by HR-pQCT. The highest integration time

A TALE-inspired computational screen for proteins that contain approximate tandem repeats.

Science.gov (United States)

Perycz, Malgorzata; Krwawicz, Joanna; Bochtler, Matthias

2017-01-01

TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen.

The Jasmonate-ZIM-Domain Proteins Interact with the WD-Repeat/bHLH/MYB Complexes to Regulate Jasmonate-Mediated Anthocyanin Accumulation and Trichome Initiation in Arabidopsis thaliana[C][W

Science.gov (United States)

Qi, Tiancong; Song, Susheng; Ren, Qingcuo; Wu, Dewei; Huang, Huang; Chen, Yan; Fan, Meng; Peng, Wen; Ren, Chunmei; Xie, Daoxin

2011-01-01

Jasmonates (JAs) mediate plant responses to insect attack, wounding, pathogen infection, stress, and UV damage and regulate plant fertility, anthocyanin accumulation, trichome formation, and many other plant developmental processes. Arabidopsis thaliana Jasmonate ZIM-domain (JAZ) proteins, substrates of the CORONATINE INSENSITIVE1 (COI1)–based SCFCOI1 complex, negatively regulate these plant responses. Little is known about the molecular mechanism for JA regulation of anthocyanin accumulation and trichome initiation. In this study, we revealed that JAZ proteins interact with bHLH (Transparent Testa8, Glabra3 [GL3], and Enhancer of Glabra3 [EGL3]) and R2R3 MYB transcription factors (MYB75 and Glabra1), essential components of WD-repeat/bHLH/MYB transcriptional complexes, to repress JA-regulated anthocyanin accumulation and trichome initiation. Genetic and physiological evidence showed that JA regulates WD-repeat/bHLH/MYB complex-mediated anthocyanin accumulation and trichome initiation in a COI1-dependent manner. Overexpression of the MYB transcription factor MYB75 and bHLH factors (GL3 and EGL3) restored anthocyanin accumulation and trichome initiation in the coi1 mutant, respectively. We speculate that the JA-induced degradation of JAZ proteins abolishes the interactions of JAZ proteins with bHLH and MYB factors, allowing the transcriptional function of WD-repeat/bHLH/MYB complexes, which subsequently activate respective downstream signal cascades to modulate anthocyanin accumulation and trichome initiation. PMID:21551388

Journeys on the H-R diagram

International Nuclear Information System (INIS)

Kaler, J.B.

1988-01-01

The evolution of various types of stars along the H-R diagram is discussed. Star birth and youth is addressed, and the events that occur due to core contraction, shell burning, and double-shell burning are described. The evolutionary courses of planetary nebulae, white dwarfs, and supernovas are examined

Wives Domain-Specific "Marriage Work" with Friends and Spouses: Links to Marital Quality

Science.gov (United States)

Proulx, Christine M.; Helms, Heather M.; Payne, C. Chris

2004-01-01

This study examined the friendship experiences of 52 wives and mothers, with particular attention given to wives' marriage work (discussions about concerns and problems in the marriage) in 10 domains with friends and spouses. A series of within-subjects repeated measures analyses of variance (ANOVAs) indicated that in all but two domains, wives…

Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei

International Nuclear Information System (INIS)

Sabourin, P.J.; Sun, J.D.; MacGregor, J.T.; Wehr, C.M.; Birnbaum, L.S.; Lucier, G.; Henderson, R.F.

1990-01-01

Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1 mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were exposed to 600 ppm, 14C-labeled benzene for 6 hr. Individual benzene metabolites in urine collected for 24 hr after the exposure were analyzed. There was a significant decrease in the respiratory rate of mice (but not rats) pretreated with benzene which resulted in lower levels of urinary [14C]benzene metabolites. The analyses indicated that the only effects of benzene pretreatment on the metabolite profile in rat or mouse urine were a slight shift from glucuronidation to sulfation in mice and a shift from sulfation to glucuronidation in rats. Benzene pretreatment also had no effect, in either species, on formation of [14C]benzene-derived hemoglobin adducts. Mice and rats had similar levels of hemoglobin adduct binding, despite the higher metabolism of benzene by mice. This indicates that hemoglobin adduct formation occurs with higher efficiency in rats. After 1 week of exposure to 600 ppm benzene, the frequency of micronucleated, polychromatic erythrocytes (PCEs) in mice was significantly increased

Comments on H.R. 2480

International Nuclear Information System (INIS)

Rezendes, V.S.

1990-10-01

GAO testified on H.R. 2480, the Uranium Enrichment Reorganization Act, which would restructure DOE's uranium enrichment program as a government corporation. Specifically, this legislation would allow the corporation to set prices to maximize long-term returns; establish a fund to meet future decontamination, decommissioning, and remedial action costs associated with past uranium enrichment activities. and require the government to pay its share of the costs to clean up mining waste generated under past government contracts. GAO believes that H.R. 2480 takes needed steps toward establishing clear objectives for the enrichment program and would allow the new corporation to better operate as a business entity. The bill would also resolve several long-term issues that seriously challenge the program's future, including the need to pay billions of dollars in environmental and decommissioning costs at a time when competition is expected to increase. However, GAO believes that the bill could be strengthened by including a specific cost recovery provision. Because DOE projects that the corporation's future earnings could be substantial, GAO suggests that Congress require the repayment of $3 billion, rather than rely solely on unspecified dividends and/or uncertain future stock sales that may not materialize unless problems related to licensing uncertainties, increased competition, and billions of dollars in liabilities are adequately resolved

Structure and evolution of N-domains in AAA metalloproteases.

Science.gov (United States)

Scharfenberg, Franka; Serek-Heuberger, Justyna; Coles, Murray; Hartmann, Marcus D; Habeck, Michael; Martin, Jörg; Lupas, Andrei N; Alva, Vikram

2015-02-27

Metalloproteases of the AAA (ATPases associated with various cellular activities) family play a crucial role in protein quality control within the cytoplasmic membrane of bacteria and the inner membrane of eukaryotic organelles. These membrane-anchored hexameric enzymes are composed of an N-terminal domain with one or two transmembrane helices, a central AAA ATPase module, and a C-terminal Zn(2+)-dependent protease. While the latter two domains have been well studied, so far, little is known about the N-terminal regions. Here, in an extensive bioinformatic and structural analysis, we identified three major, non-homologous groups of N-domains in AAA metalloproteases. By far, the largest one is the FtsH-like group of bacteria and eukaryotic organelles. The other two groups are specific to Yme1: one found in plants, fungi, and basal metazoans and the other one found exclusively in animals. Using NMR and crystallography, we determined the subunit structure and hexameric assembly of Escherichia coli FtsH-N, exhibiting an unusual α+β fold, and the conserved part of fungal Yme1-N from Saccharomyces cerevisiae, revealing a tetratricopeptide repeat fold. Our bioinformatic analysis showed that, uniquely among these proteins, the N-domain of Yme1 from the cnidarian Hydra vulgaris contains both the tetratricopeptide repeat region seen in basal metazoans and a region of homology to the N-domains of animals. Thus, it is a modern-day representative of an intermediate in the evolution of animal Yme1 from basal eukaryotic precursors. Copyright © 2015. Published by Elsevier Ltd.

Acute effects of repeated bouts of aerobic exercise on arterial stiffness after glucose ingestion.

Science.gov (United States)

Kobayashi, Ryota; Hashimoto, Yuto; Hatakeyama, Hiroyuki; Okamoto, Takanobu

2018-03-22

The aim of this study was to investigate the acute repeated bouts of aerobic exercise decrease leg arterial stiffness. However, the influence of repeated bouts of aerobic exercise on arterial stiffness after glucose ingestion is unknown. The present study investigates the acute effects of repeated bouts of aerobic exercise on arterial stiffness after the 75-g oral glucose tolerance test (OGTT). Ten healthy young men (age, 23.2 ± 0.9 years) performed repeated bouts of aerobic exercise trial (RE, 65% peak oxygen uptake; two 15 min bouts of cycling performed 20 min apart) and control trial (CON, seated and resting in a quiet room) at 80 min before the 75-g OGTT on separate days in a randomized, controlled crossover fashion. Carotid-femoral (aortic) and femoral-ankle (leg) pulse wave velocity, carotid augmentation index, brachial and ankle blood pressure, heart rate and blood glucose and insulin levels were measured before (baseline) and 30, 60 and 120 min after the 75-g OGTT. Leg pulse wave velocity, ankle systolic blood pressure and blood glucose levels increased from baseline after the 75-g OGTT in the CON trial, but not in the RE trial. The present findings indicate that acute repeated bouts of aerobic exercise before glucose ingestion suppress increases in leg arterial stiffness following glucose ingestion. RE trial repeated bouts of aerobic exercise trial; CON trial control trial; BG blood glucose; VO 2peak peak oxygen uptake; PWV Pulse wave velocity; AIx carotid augmentation index; BP blood pressure; HR heart rate; CVs coefficients of variation; RPE Ratings of perceived exertion; SE standard error.

Synergistic enhancement of cellulase pairs linked by consensus ankyrin repeats: Determination of the roles of spacing, orientation, and enzyme identity.

Science.gov (United States)

Cunha, Eva S; Hatem, Christine L; Barrick, Doug

2016-08-01

Biomass deconstruction to small simple sugars is a potential approach to biofuels production; however, the highly recalcitrant nature of biomass limits the economic viability of this approach. Thus, research on efficient biomass degradation is necessary to achieve large-scale production of biofuels. Enhancement of cellulolytic activity by increasing synergism between cellulase enzymes holds promise in achieving high-yield biofuels production. Here we have inserted cellulase pairs from extremophiles into hyperstable α-helical consensus ankyrin repeat domain scaffolds. Such chimeric constructs allowed us to optimize arrays of enzyme pairs against a variety of cellulolytic substrates. We found that endocellulolytic domains CelA (CA) and Cel12A (C12A) act synergistically in the context of ankyrin repeats, with both three and four repeat spacing. The extent of synergy differs for different substrates. Also, having C12A N-terminal to CA provides greater synergy than the reverse construct, especially against filter paper. In contrast, we do not see synergy for these enzymes in tandem with CelK (CK) catalytic domain, a larger exocellulase, demonstrating the importance of enzyme identity in synergistic enhancement. Furthermore, we found endocellulases CelD and CA with three repeat spacing to act synergistically against filter paper. Importantly, connecting CA and C12A with a disordered linker of similar contour length shows no synergistic enhancement, indicating that synergism results from connecting these domains with folded ankyrin repeats. These results show that ankyrin arrays can be used to vary spacing and orientation between enzymes, helping to design and optimize artificial cellulosomes, providing a novel architecture for synergistic enhancement of enzymatic cellulose degradation. Proteins 2016; 84:1043-1054. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Control of coercive field in lithium niobate crystals with repeated polarization reversal

International Nuclear Information System (INIS)

Ro, Jung Hoon; Jeong, Doun; Park, Taeyong; Kim, Chulhan; Kwon, Soon-Bok; Cha, Myoungsik; Choi, Byeong Cheol; Yu, Nanei; Kurimura, Sunao; Jeon, Gyerok

2005-01-01

In this study, the amount of decrease in coercive field of congruent lithium niobate during repeated poling and back-poling was measured. The polarization is reversed in 300 ms and then back-poled during the rest period. The coercive field can be decreased around 1 kV/mm with a repeated poling interval of 5 s. As the interval prolonged, the poling field decrease became smaller, and a stretched exponential function is suggested for the experimental fitting resulting in a set of meaningful parameters. These values are essential for the design of high quality domain engineering

The polymorphic integumentary mucin B.1 from Xenopus laevis contains the short consensus repeat.

Science.gov (United States)

Probst, J C; Hauser, F; Joba, W; Hoffmann, W

1992-03-25

The frog integumentary mucin B.1 (FIM-B.1), discovered by molecular cloning, contains a cysteine-rich C-terminal domain which is homologous with von Willebrand factor. With the help of the polymerase chain reaction, we now characterize a contiguous region 5' to the von Willebrand factor domain containing the short consensus repeat typical of many proteins from the complement system. Multiple transcripts have been cloned, which originate from a single animal and differ by a variable number of tandem repeats (rep-33 sequences). These different transcripts probably originate solely from two genes and are generated presumably by alternative splicing of an huge array of functional cassettes. This model is supported by analysis of genomic FIM-B.1 sequences from Xenopus laevis. Here, rep-33 sequences are arranged in an interrupted array of individual units. Additionally, results of Southern analysis revealed genetic polymorphism between different animals which is predicted to be within the tandem repeats. A first investigation of the predicted mucins with the help of a specific antibody against a synthetic peptide determined the molecular mass of FIM-B.1 to greater than 200 kDa. Here again, genetic polymorphism between different animals is detected.

Esprit HR mattress cover in pressure ulcer prevention.

Science.gov (United States)

Khoulowa, J

Modern mattresses provide soft dense foam, which permits the redistribution of pressure on the patient over a wider area - away from bony prominences where pressure ulcers usually occur. The material used in producing multistretch covers for the new mattresses had a tendency to delaminate as a result of a combination of heat, moisture and inappropriate cleansing techniques causing the water barriers to fall. In partnership with York Health NHS Trust and the material manufacturer, STM Healthcare produced a mattress cover (Esprit HR) which was able to withstand higher pressure from heat and moisture and greatly extended the life expectancy of the Esprit HR mattress.

The RTR Complex Partner RMI2 and the DNA Helicase RTEL1 Are Both Independently Involved in Preserving the Stability of 45S rDNA Repeats in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Sarah Röhrig

2016-10-01

Full Text Available The stability of repetitive sequences in complex eukaryotic genomes is safeguarded by factors suppressing homologues recombination. Prominent in this is the role of the RTR complex. In plants, it consists of the RecQ helicase RECQ4A, the topoisomerase TOP3α and RMI1. Like mammals, but not yeast, plants harbor an additional complex partner, RMI2. Here, we demonstrate that, in Arabidopsis thaliana, RMI2 is involved in the repair of aberrant replication intermediates in root meristems as well as in intrastrand crosslink repair. In both instances, RMI2 is involved independently of the DNA helicase RTEL1. Surprisingly, simultaneous loss of RMI2 and RTEL1 leads to loss of male fertility. As both the RTR complex and RTEL1 are involved in suppression of homologous recombination (HR, we tested the efficiency of HR in the double mutant rmi2-2 rtel1-1 and found a synergistic enhancement (80-fold. Searching for natural target sequences we found that RTEL1 is required for stabilizing 45S rDNA repeats. In the double mutant with rmi2-2 the number of 45S rDNA repeats is further decreased sustaining independent roles of both factors in this process. Thus, loss of suppression of HR does not only lead to a destabilization of rDNA repeats but might be especially deleterious for tissues undergoing multiple cell divisions such as the male germline.

The RTR Complex Partner RMI2 and the DNA Helicase RTEL1 Are Both Independently Involved in Preserving the Stability of 45S rDNA Repeats in Arabidopsis thaliana.

Science.gov (United States)

Röhrig, Sarah; Schröpfer, Susan; Knoll, Alexander; Puchta, Holger

2016-10-01

The stability of repetitive sequences in complex eukaryotic genomes is safeguarded by factors suppressing homologues recombination. Prominent in this is the role of the RTR complex. In plants, it consists of the RecQ helicase RECQ4A, the topoisomerase TOP3α and RMI1. Like mammals, but not yeast, plants harbor an additional complex partner, RMI2. Here, we demonstrate that, in Arabidopsis thaliana, RMI2 is involved in the repair of aberrant replication intermediates in root meristems as well as in intrastrand crosslink repair. In both instances, RMI2 is involved independently of the DNA helicase RTEL1. Surprisingly, simultaneous loss of RMI2 and RTEL1 leads to loss of male fertility. As both the RTR complex and RTEL1 are involved in suppression of homologous recombination (HR), we tested the efficiency of HR in the double mutant rmi2-2 rtel1-1 and found a synergistic enhancement (80-fold). Searching for natural target sequences we found that RTEL1 is required for stabilizing 45S rDNA repeats. In the double mutant with rmi2-2 the number of 45S rDNA repeats is further decreased sustaining independent roles of both factors in this process. Thus, loss of suppression of HR does not only lead to a destabilization of rDNA repeats but might be especially deleterious for tissues undergoing multiple cell divisions such as the male germline.

PLEIADES-HR INNOVATIVE TECHNIQUES FOR RADIOMETRIC IMAGE QUALITY COMMISSIONING

Directory of Open Access Journals (Sweden)

G. Blanchet

2012-07-01

Full Text Available The first Pleiades-HR satellite, part of a constellation of two, has been launched on December 17, 2011. This satellite produces high resolution optical images. In order to achieve good image quality, Pleiades-HR should first undergo an important 6 month commissioning phase period. This phase consists in calibrating and assessing the radiometric and geometric image quality to offer the best images to end users. This new satellite has benefited from technology improvements in various fields which make it stand out from other Earth observation satellites. In particular, its best-in-class agility performance enables new calibration and assessment techniques. This paper is dedicated to presenting these innovative techniques that have been tested for the first time for the Pleiades- HR radiometric commissioning. Radiometric activities concern compression, absolute calibration, detector normalization, and refocusing operations, MTF (Modulation Transfer Function assessment, signal-to-noise ratio (SNR estimation, and tuning of the ground processing parameters. The radiometric performances of each activity are summarized in this paper.

A nonlinear filtering algorithm for denoising HR(S)TEM micrographs

International Nuclear Information System (INIS)

Du, Hongchu

2015-01-01

Noise reduction of micrographs is often an essential task in high resolution (scanning) transmission electron microscopy (HR(S)TEM) either for a higher visual quality or for a more accurate quantification. Since HR(S)TEM studies are often aimed at resolving periodic atomistic columns and their non-periodic deviation at defects, it is important to develop a noise reduction algorithm that can simultaneously handle both periodic and non-periodic features properly. In this work, a nonlinear filtering algorithm is developed based on widely used techniques of low-pass filter and Wiener filter, which can efficiently reduce noise without noticeable artifacts even in HR(S)TEM micrographs with contrast of variation of background and defects. The developed nonlinear filtering algorithm is particularly suitable for quantitative electron microscopy, and is also of great interest for beam sensitive samples, in situ analyses, and atomic resolution EFTEM. - Highlights: • A nonlinear filtering algorithm for denoising HR(S)TEM images is developed. • It can simultaneously handle both periodic and non-periodic features properly. • It is particularly suitable for quantitative electron microscopy. • It is of great interest for beam sensitive samples, in situ analyses, and atomic resolution EFTEM

Bringing human resources to the table: utilization of an HR balanced scorecard at Mayo Clinic.

Science.gov (United States)

Fottler, Myron D; Erickson, Eric; Rivers, Patrick A

2006-01-01

Rather than viewing HR as a critical driver of organizational strategy and outcomes, most health care organizations see HR as a drain on the organization's bottom line. Only by aligning HR with the organizational strategy will HR leaders truly get a seat at the leadership table. HR professionals can overcome impediments and gain a seat at the table by learning the language of business and the ways in which organizational leaders use data to drive their decisions. This article shows how Mayo Clinic uses the popular Balanced Scorecard approach to align its measures of HR performance to the organization's strategic plan.

Comparison between Pentacam HR and Orbscan II after hyperopic photorefractive keratectomy

Directory of Open Access Journals (Sweden)

Mahmoud Jabbarvand

2017-01-01

Conclusion: Pentacam HR and Orbscan II after PRK for hyperopia show reasonable agreement for determining A-BFS, P-BFS, A-TG3, and CCT, but not for A-CE, P-CE, A-TG5, or ACD. CCT measurements with Pentacam HR have reasonable agreement with US pachymetry.

The TIR domain of TIR-NB-LRR resistance proteins is a signaling domain involved in cell death induction.

Science.gov (United States)

Swiderski, Michal R; Birker, Doris; Jones, Jonathan D G

2009-02-01

In plants, the TIR (toll interleukin 1 receptor) domain is found almost exclusively in nucleotide-binding (NB) leucine-rich repeat resistance proteins and their truncated homologs, and has been proposed to play a signaling role during resistance responses mediated by TIR containing R proteins. Transient expression in Nicotiana benthamiana leaves of "TIR + 80", the RPS4 truncation without the NB-ARC domain, leads to EDS1-, SGT1-, and HSP90-dependent cell death. Transgenic Arabidopsis plants expressing the RPS4 TIR+80 from either dexamethasone or estradiol-inducible promoters display inducer-dependent cell death. Cell death is also elicited by transient expression of similarly truncated constructs from two other R proteins, RPP1A and At4g19530, but is not elicited by similar constructs representing RPP2A and RPP2B proteins. Site-directed mutagenesis of the RPS4 TIR domain identified many loss-of-function mutations but also revealed several gain-of function substitutions. Lack of cell death induction by the E160A substitution suggests that amino acids outside of the TIR domain contribute to cell death signaling in addition to the TIR domain itself. This is consistent with previous observations that the TIR domain itself is insufficient to induce cell death upon transient expression.

Deletion of intragenic tandem repeats in unit C of FLO1 of Saccharomyces cerevisiae increases the conformational stability of flocculin under acidic and alkaline conditions.

Directory of Open Access Journals (Sweden)

Ee Li

Full Text Available Flocculation is an attractive property for Saccaromyces cerevisiae, which plays important roles in fermentation industry and environmental remediation. The process of flocculation is mediated by a family of cell surface flocculins. As one member of flocculins, Flo1 is characterized by four families of repeats (designated as repeat units A, B, C and D in the central domain. It is generally accepted that variation of repeat unit A in length in Flo1 influences the degree of flocculation or specificity for sugar recognization. However, no reports were observed for other repeat units. Here, we compared the flocculation ability and its sensitivity to environmental factors between yeast strain YSF1 carrying the intact FLO1 gene and yeast strains carrying the derived forms of FLO1 with partial or complete deletion of repeats in unit C. No obvious differences in flocculation ability and specificity of carbohydrate recognition were observed among these yeast strains, which indicates the truncated flocculins can stride across the cell wall and cluster the N-terminal domain on the surface of yeast cells as the intact Flo1 thereby improving intercellular binding. However, yeast strains with the truncated flocculins required more mannose to inhibit completely the flocculation, displayed broad tolerance of flocculation to pH fluctuation, and the fewer the repeats in unit C, the stronger adaptability of flocculation to pH change, which was not relevant to the position of deletion. This suggests that more stable active conformation is obtained for flocculin by deletion the repeat unit C in the central domain of Flo1, which was validated further by the higher hydrophobicity on the surface of cells of YSF1c with complete deletion of unit C under neutral and alkaline conditions and the stabilization of GFP conformation by fusion with flocculin with complete deletion of unit C in the central domain.

Distribution of ABO and Rh-Hr blood group antigens, alleles and ...

African Journals Online (AJOL)

ABO and Rh-Hr blood group antigens represent a genetically stably determined trait with many-sided biological and clinical significance. The indigenous Ajarian population (105 subjects) was investigated for ABO Rh-Hr red cell blood group antigens. Using immunoserologic methods, seven blood group antigens (A, B, C, c, ...

Dominant integration locus drives continuous diversification of plant immune receptors with exogenous domain fusions.

Science.gov (United States)

Bailey, Paul C; Schudoma, Christian; Jackson, William; Baggs, Erin; Dagdas, Gulay; Haerty, Wilfried; Moscou, Matthew; Krasileva, Ksenia V

2018-02-19

The plant immune system is innate and encoded in the germline. Using it efficiently, plants are capable of recognizing a diverse range of rapidly evolving pathogens. A recently described phenomenon shows that plant immune receptors are able to recognize pathogen effectors through the acquisition of exogenous protein domains from other plant genes. We show that plant immune receptors with integrated domains are distributed unevenly across their phylogeny in grasses. Using phylogenetic analysis, we uncover a major integration clade, whose members underwent repeated independent integration events producing diverse fusions. This clade is ancestral in grasses with members often found on syntenic chromosomes. Analyses of these fusion events reveals that homologous receptors can be fused to diverse domains. Furthermore, we discover a 43 amino acid long motif associated with this dominant integration clade which is located immediately upstream of the fusion site. Sequence analysis reveals that DNA transposition and/or ectopic recombination are the most likely mechanisms of formation for nucleotide binding leucine rich repeat proteins with integrated domains. The identification of this subclass of plant immune receptors that is naturally adapted to new domain integration will inform biotechnological approaches for generating synthetic receptors with novel pathogen "baits."

LBT observations of the HR8799 planetary system

Science.gov (United States)

Mesa, D.; Arcidiacono, C.; Claudi, R. U.; Desidera, S.; Esposito, S.; Gratton, R.; Masciadri, E.

2013-09-01

We present here observations of the HR8799 planetary system performed in H and Ks band exploiting the AO system at the Large Binocular Telescope and the PISCES camera. Thanks to the excellent performence of the instrument we were able to detect for the first time the inner known planet of the system (HR8799) in the H band. Precise photometric and astrometric measures have been taken for all the four planets. Further, exploiting ours and previous astrometric results, we were able to put some limits on the planetary orbits of the four planets. The analysis of the dinamical stability of the system seems to show lower planetary masses than the ones adopted until now.

WD-repeat instability and diversification of the Podospora anserina hnwd non-self recognition gene family.

Science.gov (United States)

Chevanne, Damien; Saupe, Sven J; Clavé, Corinne; Paoletti, Mathieu

2010-05-06

Genes involved in non-self recognition and host defence are typically capable of rapid diversification and exploit specialized genetic mechanism to that end. Fungi display a non-self recognition phenomenon termed heterokaryon incompatibility that operates when cells of unlike genotype fuse and leads to the cell death of the fusion cell. In the fungus Podospora anserina, three genes controlling this allorecognition process het-d, het-e and het-r are paralogs belonging to the same hnwd gene family. HNWD proteins are STAND proteins (signal transduction NTPase with multiple domains) that display a WD-repeat domain controlling recognition specificity. Based on genomic sequence analysis of different P. anserina isolates, it was established that repeat regions of all members of the gene family are extremely polymorphic and undergoing concerted evolution arguing for frequent recombination within and between family members. Herein, we directly analyzed the genetic instability and diversification of this allorecognition gene family. We have constituted a collection of 143 spontaneous mutants of the het-R (HNWD2) and het-E (hnwd5) genes with altered recognition specificities. The vast majority of the mutants present rearrangements in the repeat arrays with deletions, duplications and other modifications as well as creation of novel repeat unit variants. We investigate the extreme genetic instability of these genes and provide a direct illustration of the diversification strategy of this eukaryotic allorecognition gene family.

Mexican Cervical Cancer Screening Study II: 6-month and 2-year follow-up of HR-HPV women treated with cryotherapy in a low-resource setting.

Science.gov (United States)

Starks, David; Arriba, Lucybeth Nieves; Enerson, Christine L; Brainard, Jennifer; Nagore, Norma; Chiesa-Vottero, Andres; Uribe, Jesús Villagran; Belinson, Jerome

2014-10-01

To determine the efficacy and tolerance of cryotherapy in a visual inspection with acetic acid (VIA) triage protocol after primary human papillomavirus (HPV) screening in a low-resource setting. This continuous series conducted over 2 years enrolled nonpregnant, high-risk HPV (HR-HPV)-positive women between the ages of 30 and 50 years, who resided in the state of Michoacán, Mexico, and had a history of no Pap smear screening or knowledge of Pap smear results within the last 3 years. These women were initially enrolled in the Mexican Cervical Cancer Screening Study II (MECCS II) trial and were treated with cryotherapy after VIA triage. They subsequently followed up at 6 months and 2 years for repeat VIA, colposcopy, and biopsy. A total of 291 women were treated with cryotherapy, of whom 226 (78%) followed up at 6 months. Of these 226 women, 153 (68%) were HR-HPV-negative; there were no findings of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. The remaining 73 women (32%) were HR-HPV-positive; of these women, 2 had CIN2 and 3 had CIN3. Only 137 women followed up at 2 years. Of these 137 women, 116 were HR-HPV-negative and 21 were HR-HPV-positive. Of the 21 women positive for HR-HPV, 9 had negative biopsy results, 11 had CIN1, and 1 had no biopsy. The clearance rate of HR-HPV was 83% (95% confidence interval: 0.78-0.87). There were no biopsy findings of CIN2 or worse at 2 years. Before cryotherapy, of the 226 women, 15 (6.6%) were positive for endocervical curettage (ECC) and 5 (2.2%) were referred for surgical management. Of these 15 ECC-positive women, 10 (67%) followed up at 6 months and it was shown that no patient was ECC positive at that time point. Moreover, of the 15 ECC-positive women, 11 (73%) followed up at 2 years and it was shown that no patient was ECC positive at that time point. In our study, VIA had a false-positive rate of 5%. Cryotherapy was an effective, acceptable, and well-tolerated means of treating cervical dysplasia in a low

Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain.

Science.gov (United States)

Moparthi, Lavanya; Survery, Sabeen; Kreir, Mohamed; Simonsen, Charlotte; Kjellbom, Per; Högestätt, Edward D; Johanson, Urban; Zygmunt, Peter M

2014-11-25

We have purified and reconstituted human transient receptor potential (TRP) subtype A1 (hTRPA1) into lipid bilayers and recorded single-channel currents to understand its inherent thermo- and chemosensory properties as well as the role of the ankyrin repeat domain (ARD) of the N terminus in channel behavior. We report that hTRPA1 with and without its N-terminal ARD (Δ1-688 hTRPA1) is intrinsically cold-sensitive, and thus, cold-sensing properties of hTRPA1 reside outside the N-terminal ARD. We show activation of hTRPA1 by the thiol oxidant 2-((biotinoyl)amino)ethyl methanethiosulfonate (MTSEA-biotin) and that electrophilic compounds activate hTRPA1 in the presence and absence of the N-terminal ARD. The nonelectrophilic compounds menthol and the cannabinoid Δ(9)-tetrahydrocannabiorcol (C16) directly activate hTRPA1 at different sites independent of the N-terminal ARD. The TRPA1 antagonist HC030031 inhibited cold and chemical activation of hTRPA1 and Δ1-688 hTRPA1, supporting a direct interaction with hTRPA1 outside the N-terminal ARD. These findings show that hTRPA1 is an intrinsically cold- and chemosensitive ion channel. Thus, second messengers, including Ca(2+), or accessory proteins are not needed for hTRPA1 responses to cold or chemical activators. We suggest that conformational changes outside the N-terminal ARD by cold, electrophiles, and nonelectrophiles are important in hTRPA1 channel gating and that targeting chemical interaction sites outside the N-terminal ARD provides possibilities to fine tune TRPA1-based drug therapies (e.g., for treatment of pain associated with cold hypersensitivity and cardiovascular disease).

Solution structure of leptospiral LigA4 Big domain

Energy Technology Data Exchange (ETDEWEB)

Mei, Song; Zhang, Jiahai [Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhang, Xuecheng [School of Life Sciences, Anhui University, Hefei, Anhui 230039 (China); Tu, Xiaoming, E-mail: xmtu@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China)

2015-11-13

Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Big domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca{sup 2+} binding property of LigA4 Big domain. - Highlights: • Determining the solution structure of a bacterial immunoglobulin-like domain from a surface protein of Leptospira. • The solution structure shows some structural characteristics significantly different from the classic Ig-like domains. • A potential Ca{sup 2+}-binding site was identified by strains-all and NMR chemical shift perturbation.

Solution structure of leptospiral LigA4 Big domain

International Nuclear Information System (INIS)

Mei, Song; Zhang, Jiahai; Zhang, Xuecheng; Tu, Xiaoming

2015-01-01

Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Big domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca"2"+ binding property of LigA4 Big domain. - Highlights: • Determining the solution structure of a bacterial immunoglobulin-like domain from a surface protein of Leptospira. • The solution structure shows some structural characteristics significantly different from the classic Ig-like domains. • A potential Ca"2"+-binding site was identified by strains-all and NMR chemical shift perturbation.

Molecular dynamics of Middle East Respiratory Syndrome Coronavirus (MERS CoV) fusion heptad repeat trimers

KAUST Repository

Kandeel, Mahmoud; Al-Taher, Abdulla; Li, Huifang; Schwingenschlö gl, Udo; Alnazawi, Mohamed

2018-01-01

Structural studies related to Middle East Respiratory Syndrome Coronavirus (MERS CoV) infection process are so limited. In this study, molecular dynamics (MD) simulation was carried out to unravel changes in the MERS CoV heptad repeat domains (HRs

Size matters: Associations between the androgen receptor CAG repeat length and the intrafollicular hormone milieu

DEFF Research Database (Denmark)

Borgbo, T; Macek, M; Chrudimska, J

2015-01-01

Granulosa cell (GC) expressed androgen receptors (AR) and intrafollicular androgens are central to fertility. The transactivating domain of the AR contains a polymorphic CAG repeat sequence, which is linked to the transcriptional activity of AR and may influence the GC function. This study aims...... to evaluate the effects of the AR CAG repeat length on the intrafollicular hormone profiles, and the gene expression profiles of GC from human small antral follicles. In total, 190 small antral follicles (3-11 mm in diameter) were collected from 58 women undergoing ovarian cryopreservation for fertility...... expression compared to medium CAG repeat lengths (P = 0.03). In conclusion, long CAG repeat lengths in the AR were associated to significant attenuated levels of androgens and an increased conversion of testosterone into oestradiol, in human small antral follicles....

阴道滴虫与宫颈HR-HPV感染及宫颈癌发生的相关性%Association about Trichomonas, HR-HPV Infection and Cervical Carcinoma

Institute of Scientific and Technical Information of China (English)

李旻; 郭会芹; 陈凤; 曹箭; 李中林; 张询; 潘秦镜

2007-01-01

目的 探讨阴道滴虫是否能增加高危人乳头瘤病毒(HR-HPV)感染和宫颈癌发生的危险.方法 对受检者进行液基细胞学检查和HR-HPV DNA检测,并在细胞学诊断中记录是否存在滴虫.对所有细胞学诊断非典型鳞状细胞(ASC)及以上病变、HR-HPV DNA阳性病例和部分细胞学阴性及HR-HPV DNA阴性病例进行阴道镜检查及活检.分别比较滴虫在HR-HPV DNA阳性组和阴性组、细胞学及组织学各级诊断中的存在率.结果 在13 024例受检者中有1 687例(12.95%)涂片中有滴虫.滴虫存在率在HR-HPV DNA阳性组与阴性组中无显著统计学差异(P＞0.05),在细胞学阴性病例组显著高于鳞状上皮内病变组(P＜0.05),在组织学阴性病例组显著高于在≥CIN2病例组(P＜0.05).结论 滴虫的存在不增加HR-HPV感染率,也不增加宫颈癌发生的危险.

HR practices for enhancing sustainable employability : implementation, use, and outcomes

OpenAIRE

Ybema, Jan Fekke; van Vuuren, Tinka; van Dam, Karen

2017-01-01

With the aging of the workforce, organizations need to maintain or improve the sustainable employability of their workforce throughout their working life. This raises the question which HR practices increase workers’ sustainable employability at work. The aim of this study is to investigate the extent to which organizations implement HR practices for enhancing sustainable employability in terms of workers’ health, motivation, and skills and knowledge from the employer’s perspective. In total,...

The composite nature of the peculiar star HR 6560 (HD 159870)

Science.gov (United States)

Wegner, Gary; Cowley, Charles R.

1992-01-01

Ground-based high-dispersion photographic spectra and ultraviolet spectra obtained with the IUE satellite are described and employed to determine the nature of the peculiar star HR 6560 (HD 159870). Previously this object had been described as both a composite system and as a strong Fm star. The UBVRI, Stromgren, and ultraviolet colors of HR 6560 are compared with objects classified composite from the Bright Star Catalogue and normal dwarfs and giants. The colors of HR 6560 are not unusual for a composite and are consistent with a late-A dwarf, combined with a late-G or early-K giant. The ultraviolet satellite clearly shows the presence of an A component, but its precise spectral type is difficult to assign. The IUE and TD-1 data suggest that the ultraviolet is dominated by light from an A5 V secondary and the visual from a GO III primary. This does not agree well with the most plausible model that fits the visual photometry. The peculiar nature of HR 6560's spectrum is most likely due to its composite nature.

Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

Directory of Open Access Journals (Sweden)

Hua Wan

2016-01-01

Full Text Available TAL effectors (TALEs contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE.

Interactions between the S-domain receptor kinases and AtPUB-ARM E3 ubiquitin ligases suggest a conserved signaling pathway in Arabidopsis.

Science.gov (United States)

Samuel, Marcus A; Mudgil, Yashwanti; Salt, Jennifer N; Delmas, Frédéric; Ramachandran, Shaliny; Chilelli, Andrea; Goring, Daphne R

2008-08-01

The Arabidopsis (Arabidopsis thaliana) genome encompasses multiple receptor kinase families with highly variable extracellular domains. Despite their large numbers, the various ligands and the downstream interacting partners for these kinases have been deciphered only for a few members. One such member, the S-receptor kinase, is known to mediate the self-incompatibility (SI) response in Brassica. S-receptor kinase has been shown to interact and phosphorylate a U-box/ARM-repeat-containing E3 ligase, ARC1, which, in turn, acts as a positive regulator of the SI response. In an effort to identify conserved signaling pathways in Arabidopsis, we performed yeast two-hybrid analyses of various S-domain receptor kinase family members with representative Arabidopsis plant U-box/ARM-repeat (AtPUB-ARM) E3 ligases. The kinase domains from S-domain receptor kinases were found to interact with ARM-repeat domains from AtPUB-ARM proteins. These kinase domains, along with M-locus protein kinase, a positive regulator of SI response, were also able to phosphorylate the ARM-repeat domains in in vitro phosphorylation assays. Subcellular localization patterns were investigated using transient expression assays in tobacco (Nicotiana tabacum) BY-2 cells and changes were detected in the presence of interacting kinases. Finally, potential links to the involvement of these interacting modules to the hormone abscisic acid (ABA) were investigated. Interestingly, AtPUB9 displayed redistribution to the plasma membrane of BY-2 cells when either treated with ABA or coexpressed with the active kinase domain of ARK1. As well, T-DNA insertion mutants for ARK1 and AtPUB9 lines were altered in their ABA sensitivity during germination and acted at or upstream of ABI3, indicating potential involvement of these proteins in ABA responses.

Crystal Structure of the HEAT Domain from the Pre-mRNA Processing Factor Symplekin

Energy Technology Data Exchange (ETDEWEB)

Kennedy, Sarah A.; Frazier, Monica L.; Steiniger, Mindy; Mast, Ann M.; Marzluff, William F.; Redinbo, Matthew R.; (UNC)

2010-09-30

The majority of eukaryotic pre-mRNAs are processed by 3'-end cleavage and polyadenylation, although in metazoa the replication-dependent histone mRNAs are processed by 3'-end cleavage but not polyadenylation. The macromolecular complex responsible for processing both canonical and histone pre-mRNAs contains the {approx} 1160-residue protein Symplekin. Secondary-structural prediction algorithms identified putative HEAT domains in the 300 N-terminal residues of all Symplekins of known sequence. The structure and dynamics of this domain were investigated to begin elucidating the role Symplekin plays in mRNA maturation. The crystal structure of the Drosophila melanogaster Symplekin HEAT domain was determined to 2.4 {angstrom} resolution with single-wavelength anomalous dispersion phasing methods. The structure exhibits five canonical HEAT repeats along with an extended 31-amino-acid loop (loop 8) between the fourth and fifth repeat that is conserved within closely related Symplekin sequences. Molecular dynamics simulations of this domain show that the presence of loop 8 dampens correlated and anticorrelated motion in the HEAT domain, therefore providing a neutral surface for potential protein-protein interactions. HEAT domains are often employed for such macromolecular contacts. The Symplekin HEAT region not only structurally aligns with several established scaffolding proteins, but also has been reported to contact proteins essential for regulating 3'-end processing. Together, these data support the conclusion that the Symplekin HEAT domain serves as a scaffold for protein-protein interactions essential to the mRNA maturation process.

[Family of ribosomal proteins S1 contains unique conservative domain].

Science.gov (United States)

Deriusheva, E I; Machulin, A V; Selivanova, O M; Serdiuk, I N

2010-01-01

Different representatives of bacteria have different number of amino acid residues in the ribosomal proteins S1. This number varies from 111 (Spiroplasma kunkelii) to 863 a.a. (Treponema pallidum). Traditionally and for lack of this protein three-dimensional structure, its architecture is represented as repeating S1 domains. Number of these domains depends on the protein's length. Domain's quantity and its boundaries data are contained in the specialized databases, such as SMART, Pfam and PROSITE. However, for the same object these data may be very different. For search of domain's quantity and its boundaries, new approach, based on the analysis of dicted secondary structure (PsiPred), was used. This approach allowed us to reveal structural domains in amino acid sequences of S1 proteins and at that number varied from one to six. Alignment of S1 proteins, containing different domain's number, with the S1 RNAbinding domain of Escherichia coli PNPase elicited a fact that in family of ribosomal proteins SI one domain has maximal homology with S1 domain from PNPase. This conservative domain migrates along polypeptide chain and locates in proteins, containing different domain's number, according to specified pattern. In this domain as well in the S1 domain from PNPase, residues Phe-19, Phe-22, His-34, Asp-64 and Arg-68 are clustered on the surface and formed RNA binding site.

t2prhd: a tool to study the patterns of repeat evolution

Directory of Open Access Journals (Sweden)

Pénzes Zsolt

2008-01-01

Full Text Available Abstract Background The models developed to characterize the evolution of multigene families (such as the birth-and-death and the concerted models have also been applied on the level of sequence repeats inside a gene/protein. Phylogenetic reconstruction is the method of choice to study the evolution of gene families and also sequence repeats in the light of these models. The characterization of the gene family evolution in view of the evolutionary models is done by the evaluation of the clustering of the sequences with the originating loci in mind. As the locus represents positional information, it is straightforward that in the case of the repeats the exact position in the sequence should be used, as the simple numbering according to repeat order can be misleading. Results We have developed a novel rapid visual approach to study repeat evolution, that takes into account the exact repeat position in a sequence. The "pairwise repeat homology diagram" visualizes sequence repeats detected by a profile HMM in a pair of sequences and highlights their homology relations inferred by a phylogenetic tree. The method is implemented in a Perl script (t2prhd available for downloading at http://t2prhd.sourceforge.net and is also accessible as an online tool at http://t2prhd.brc.hu. The power of the method is demonstrated on the EGF-like and fibronectin-III-like (Fn-III domain repeats of three selected mammalian Tenascin sequences. Conclusion Although pairwise repeat homology diagrams do not carry all the information provided by the phylogenetic tree, they allow a rapid and intuitive assessment of repeat evolution. We believe, that t2prhd is a helpful tool with which to study the pattern of repeat evolution. This method can be particularly useful in cases of large datasets (such as large gene families, as the command line interface makes it possible to automate the generation of pairwise repeat homology diagrams with the aid of scripts.

Classification of Ap-stars HR 830 and ZI CVn

International Nuclear Information System (INIS)

Zverko, J.

1984-01-01

Two ambiguously classified Ap-stars, HR 830 and 21 CVn, are studied. The observational data are compared with the data for normal stars αDel and αLyr. Star HR 830 is classified as Ap of type Si based on the enhanced absorption in the Si lines and photometric variability in UBV. 21 CVn is classified as Ap Si based on weaker absorption of helium, the variability of helium lines, photometric periodic variability and the properties of the UV spectrum. It is concluded that the photometric periodic variability is a good indicator of Ap-properties of rapidly rotating A and late B stars. (author)

Safety of DOE nuclear facilities. Hearings before the Subcommittee on Energy and Power of the Committee on Energy and Commerce, House of Representatives, One Hundredth Congress, First Session, H.R. 783, H.R. 2047 and H.R. 3123, November 5 and 19, 1987

International Nuclear Information System (INIS)

Anon.

1988-01-01

H.R. 783 is a bill to require the Secretary of Energy to ensure the compliance of certain operations of the Department of Energy (DOE) with Federal environmental standards and for other purposes. H.R. 2047 is a bill to establish a Defense Nuclear Facilities Safety Agency in order to provide for increased standards of safety with respect to radioactive emissions resulting from activities carried out at nuclear facilities of DOE. H.R. 3123 is a bill to create an independent oversight board to ensure the safety of United States Government nuclear facilities, to apply the provisions of OSHA to certain DOE nuclear facilities, to clarify the jurisdiction and powers of Government agencies dealing with nuclear wastes, to ensure independent research on the effects of radiation on human beings, and for other purposes

Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing.

Science.gov (United States)

Sanner, Karin; Wikström, Ingrid; Gustavsson, Inger; Wilander, Erik; Lindberg, Julia Hedlund; Gyllensten, Ulf; Olovsson, Matts

2015-12-01

Self-sampling for HPV as part of primary screening is a well-tolerated method for women not attending organized Pap smear screening and could increase coverage of cervical cancer screening. To investigate if the prevalence of HR-HPV varies from day to day in infected women and if one single sample is reliable for detecting an ongoing infection. This is a prospective cohort study on 12 premenopausal and 13 postmenopausal women performing daily self-sampling for HR-HPV testing. They were all HR-HPV-positive 1-3 months ago. Postmenopausal women were sampled for 28 days and premenopausal women sampled during bleeding-free days in one menstrual cycle. A possible difference in viral load between the estrogen-dominated proliferative phase and the progesterone-dominated secretory phase was analyzed. Consistent results throughout the sampling period were observed for 19 women, with either a daily presence of HPV (14 women) or no HPV at all during the sampling period (5 women). Of 607 samples from 25 women, 596 were consistently positive or negative for HPV during the sampling period and 11 were inconsistent (2%). There was no difference in HPV copy number between the estrogen dominated proliferative or progesterone dominated secretory menstrual cycle phases. The major finding was a high degree of consistency concerning HR-HPV positivity and negativity of HR-HPV in vaginal fluid during a sustained period of daily self-sampling. It does not appear to matter whether the sample is collected in the proliferative or secretory phase. Copyright © 2015 Elsevier B.V. All rights reserved.

Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response.

Science.gov (United States)

Reinhardt, H Christian; Yaffe, Michael B

2013-09-01

Coordinated progression through the cell cycle is a complex challenge for eukaryotic cells. Following genotoxic stress, diverse molecular signals must be integrated to establish checkpoints specific for each cell cycle stage, allowing time for various types of DNA repair. Phospho-Ser/Thr-binding domains have emerged as crucial regulators of cell cycle progression and DNA damage signalling. Such domains include 14-3-3 proteins, WW domains, Polo-box domains (in PLK1), WD40 repeats (including those in the E3 ligase SCF(βTrCP)), BRCT domains (including those in BRCA1) and FHA domains (such as in CHK2 and MDC1). Progress has been made in our understanding of the motif (or motifs) that these phospho-Ser/Thr-binding domains connect with on their targets and how these interactions influence the cell cycle and DNA damage response.

Induction of transcription from the long terminal repeat of Moloney murine sarcoma provirus by UV-irradiation, x-irradiation, and phorbol ester

International Nuclear Information System (INIS)

Lin, C.S.; Goldthwait, D.A.; Samols, D.

1990-01-01

The long terminal repeat (LTR) of Moloney murine sarcoma virus (Mo-MuSV) was used as a model system to study the stress response of mammalian cells to physical carcinogens. The chloramphenicol acetyltransferase (CAT) gene was inserted between two Mo-MuSV LTRs, and the LTR-CAT-LTR construct was used for virus production and was integrated into the genome of NIH 3T3 cells in the proviral form. This construct was used to assure that the integrated CAT gene was driven by the promoter of the LTR. Expression of the CAT gene was stimulated 4-fold by UV irradiation, and the peak of activity was observed at 18 hr. In contrast, stimulation of the CAT expression after x-irradiation was 2-fold and occurred at 6 hr. Phorbol myristate acetate also stimulated CAT activity 4-fold with a peak at 6 hr. Down-regulation of protein kinase C blocked totally the response to x-irradiation but only partially the response to UV. The protein kinase inhibitor H7 blocked the response to treatment by UV, x-ray, and phorbol ester

Qualitative risk assessment for the 100-HR-3 groundwater operable unit

Energy Technology Data Exchange (ETDEWEB)

Vukelich, S.E. [Golder Associates, Inc., Richland, WA (United States)

1994-09-22

This report provides the qualitative risk assessment for the 100-HR-3 operable unit on the Hanford Reservation. 100-HR-3 is a ground water unit. The purpose of the QRA at the 100-HR-3 operable unit is to focus on a predefined set of human and environmental exposure scenarios in order to provides sufficient information that will assist the Tri-Party signatories (Washington State Department of Ecology, EPA and US DOE) in making defensible decisions on the necessity of Interim Remedial Measures. Frequent- and occasional-use exposure scenarios are evaluated in the human health risk assessment to provide bounding estimates of risk. The ecological risk assessment consists of an evaluation of the risks to riparian and aquatic receptors which live in or near the Columbia River.

Qualitative risk assessment for the 100-HR-3 groundwater operable unit

International Nuclear Information System (INIS)

Vukelich, S.E.

1994-01-01

This report provides the qualitative risk assessment for the 100-HR-3 operable unit on the Hanford Reservation. 100-HR-3 is a ground water unit. The purpose of the QRA at the 100-HR-3 operable unit is to focus on a predefined set of human and environmental exposure scenarios in order to provides sufficient information that will assist the Tri-Party signatories (Washington State Department of Ecology, EPA and US DOE) in making defensible decisions on the necessity of Interim Remedial Measures. Frequent- and occasional-use exposure scenarios are evaluated in the human health risk assessment to provide bounding estimates of risk. The ecological risk assessment consists of an evaluation of the risks to riparian and aquatic receptors which live in or near the Columbia River

Expression, crystallization and preliminary crystallographic data analysis of filamin A repeats 14–16

International Nuclear Information System (INIS)

Aguda, Adeleke Halilu; Sakwe, Amos Malle; Rask, Lars; Robinson, Robert Charles

2007-01-01

The crystallization and crystallographic data analysis of filamin repeats 14–16 are reported. Human filamin A is a 280 kDa protein involved in actin-filament cross-linking. It is structurally divided into an actin-binding headpiece (ABD) and a rod domain containing 24 immunoglobulin-like (Ig) repeats. A fragment of human filamin A (Ig repeats 14–16) was cloned and expressed in Escherichia coli and the purified protein was crystallized in 1.6 M ammonium sulfate, 2% PEG 1000 and 100 mM HEPES pH 7.5. The crystals diffracted to 1.95 Å and belong to space group P2 1 2 1 2 1 , with unit-cell parameters a = 50.63, b = 52.10, c = 98.46 Å, α = β = γ = 90°

PASTA repeats of the protein kinase StkP interconnect cell constriction and separation of Streptococcus pneumoniae.

Science.gov (United States)

Zucchini, Laure; Mercy, Chryslène; Garcia, Pierre Simon; Cluzel, Caroline; Gueguen-Chaignon, Virginie; Galisson, Frédéric; Freton, Céline; Guiral, Sébastien; Brochier-Armanet, Céline; Gouet, Patrice; Grangeasse, Christophe

2018-02-01

Eukaryotic-like serine/threonine kinases (eSTKs) with extracellular PASTA repeats are key membrane regulators of bacterial cell division. How PASTA repeats govern eSTK activation and function remains elusive. Using evolution- and structural-guided approaches combined with cell imaging, we disentangle the role of each PASTA repeat of the eSTK StkP from Streptococcus pneumoniae. While the three membrane-proximal PASTA repeats behave as interchangeable modules required for the activation of StkP independently of cell wall binding, they also control the septal cell wall thickness. In contrast, the fourth and membrane-distal PASTA repeat directs StkP localization at the division septum and encompasses a specific motif that is critical for final cell separation through interaction with the cell wall hydrolase LytB. We propose a model in which the extracellular four-PASTA domain of StkP plays a dual function in interconnecting the phosphorylation of StkP endogenous targets along with septal cell wall remodelling to allow cell division of the pneumococcus.

International HR Strategy of Brazilian Technology Multinationals

Directory of Open Access Journals (Sweden)

Patricia Morilha Muritiba

2010-10-01

Full Text Available Four cases of Brazilian Multinationals from the information technology [IT] sector were compared in their international Human Resources strategy. The analysis is focused on the development and application of two research models. One analyzes the level of subsidiary autonomy in terms of strategic HR decisions, including difficult decisions regarding coordination in multinationals, following the theoretical approach of the autonomy of subsidiaries (Kidger, 2002; Nohria & Ghoshal, 1997. The other is related to the level of internationalization of HR strategies, defined as the capacity to take advantage of globalization, providing the best resources for the company regardless of where they are located (Sparrow, 2007. Both models were applied in a multiple case study method (Eisenhardt, 1989. Data were collected through semi-structured interviews and company reports, and analyzed through content analysis. The results show: (a a more centralizing characteristic of the multinational companies examined, despite the limitations of this choice as shown by the literature; and (b that Brazilian IT multinationals tend to rely more on their national competencies when managing human resources instead of going global to aggregate differentiated competencies.

Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

KAUST Repository

Viterbo, David; Michoud, Gregoire; Mosbach, Valentine; Dujon, Bernard; Richard, Guy-Franck

2016-01-01

Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

KAUST Repository

Viterbo, David

2016-03-16

Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

Differential binding of RhoA, RhoB, and RhoC to protein kinase C-related kinase (PRK) isoforms PRK1, PRK2, and PRK3: PRKs have the highest affinity for RhoB.

Science.gov (United States)

Hutchinson, Catherine L; Lowe, Peter N; McLaughlin, Stephen H; Mott, Helen R; Owen, Darerca

2013-11-12

Protein kinase C-related kinases (PRKs) are members of the protein kinase C superfamily of serine-threonine kinases and can be activated by binding to members of the Rho family of GTPases via a Rho-binding motif known as an HR1 domain. Three tandem HR1 domains reside at the N-terminus of the PRKs. We have assessed the ability of the HR1a and HR1b domains from the three PRK isoforms (PRK1, PRK2, and PRK3) to interact with the three Rho isoforms (RhoA, RhoB, and RhoC). The affinities of RhoA and RhoC for a construct encompassing both PRK1 HR1 domains were similar to those for the HR1a domain alone, suggesting that these interactions are mediated solely by the HR1a domain. The affinities of RhoB for both the PRK1 HR1a domain and the HR1ab didomain were higher than those of RhoA or RhoC. RhoB also bound more tightly to the didomain than to the HR1a domain alone, implicating the HR1b domain in the interaction. As compared with PRK1 HR1 domains, PRK2 and PRK3 domains bind less well to all Rho isoforms. Uniquely, however, the PRK3 domains display a specificity for RhoB that requires both the C-terminus of RhoB and the PRK3 HR1b domain. The thermal stability of the HR1a and HR1b domains was also investigated. The PRK2 HR1a domain was found to be the most thermally stable, while PRK2 HR1b, PRK3 HR1a, and PRK3 HR1b domains all exhibited lower melting temperatures, similar to that of the PRK1 HR1a domain. The lower thermal stability of the PRK2 and PRK3 HR1b domains may impart greater flexibility, driving their ability to interact with Rho isoforms.

THE IMPACT OF HR MANAGERS’ ROLES ON IMPLEMENTING BEST HR PRACTICES AND ATTRACTING AND RETAINING BEST EMPLOYEES

OpenAIRE

Nicoleta Valentina FLOREA

2014-01-01

Today’s organizations are facing new challenges, which require them to make effective decisions in order to solve complex issues. These decisions are generally made at higher levels in the organization’s hierarchical structure, where managers maintain power and control to influence organizational goals, including the behaviors and the attitudes of their subordinates. In this article we will show the importance of having effective managers, especially in HR, who can positively influence attrac...

Exploring the central characteristics of HR shared services: evidence from a critical case study in the Netherlands

NARCIS (Netherlands)

Meijerink, Jeroen Gerard; Bondarouk, Tatiana

2012-01-01

Human resource shared service centers (HR SSCs) are foreseen as improving HR service delivery for their end-users: employees, line managers and decentralized HR professionals. Although the concept expects the benefits of HR SSCs to come from centralizing knowledge and decentralizing the control

Incidence of repeat testing and diagnoses of Chlamydia trachomatis and Neisseria gonorrhoea in swingers, homosexual and heterosexual men and women at two large Dutch STI clinics, 2006-2013.

Science.gov (United States)

Dukers-Muijrers, Nicole H T M; van Rooijen, Martijn S; Hogewoning, Arjan; van Liere, Genevieve A F S; Steenbakkers, Mieke; Hoebe, Christian J P A

2017-09-01

Swingers, that is, heterosexuals who as a couple have sex with others, including group sex and bisexual behaviour, are an older-aged risk group for STIs. Here, we report on their repeat testing (reattendance) and STI yield compared with other heterosexuals and men who have sex with men (MSM, homosexual men) at two Dutch STI clinics. Swingers are routinely (since 2006, South Limburg, registration-completeness: 99%) or partially (since 2010, Amsterdam, registration-completeness: 20%) included in the clinic patient registries. Data (retrospective cohort) are analysed to assess incidence (per 100 person-years (PY)) of reattendance and STI ( Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG)) and associated factors calculating HRs. In South Limburg 7714 and in Amsterdam 2070 swinger consultations were identified. Since 2010, swingers' incidence of reattendance was 48-57/100 PY. Incidence was lower in MSM (30-39/100 PY, HR 0.56; 95% CI 0.51 to 0.61, South Limburg; HR 0.88; 95% CI 0.80 to 0.96, Amsterdam), heterosexual men (8-14/100 PY, HR 0.16; 95% CI 0.15 to 0.17, South Limburg; HR 0.33; 95% CI 0.30 to 0.36, Amsterdam) and women (13-20/100 PY, HR 0.56; 95% CI 0.51 to 0.61, South Limburg; HR 0.46; 95% CI 0.42 to 0.51, Amsterdam). Swingers' STI incidence at reattendance was 11-12/100 PY. Incidence was similar in heterosexual men (14-15/100 PY; HR 1.19; 95% CI 0.90 to 1.57, South Limburg; HR 1.20; 95% CI 0.91 to 1.59, Amsterdam) and women (12-14/100 PY; HR 1.14; 95% CI 0.88 to 1.49, South Limburg; HR 0.98; 95% CI 0.74 to 1.29, Amsterdam) and higher in MSM (18-22/100 PY; HR 1.59; 95% CI 1.19 to 2.12, South Limburg; HR 1.80; 95% CI 1.36 to 2.37, Amsterdam). Risk factors for STI incidence were partner-notified (contact-tracing), symptoms and previous STI. Swingers' positivity at any clinic attendance was 3-4% for NG (ie, higher than other heterosexuals) and 6-8% for CT (ie, lower than heterosexuals overall but higher than older heterosexuals

The 1.75 Å resolution structure of fission protein Fis1 from Saccharomyces cerevisiae reveals elusive interactions of the autoinhibitory domain

International Nuclear Information System (INIS)

Tooley, James E.; Khangulov, Victor; Lees, Jonathan P. B.; Schlessman, Jamie L.; Bewley, Maria C.; Heroux, Annie; Bosch, Jürgen; Hill, R. Blake

2011-01-01

A 1.75 Å resolution crystal structure of the Fis1 cytoplasmic domain from Saccharomyces cerevisiae is reported which adopts a tetratricopeptide-repeat fold. Fis1 mediates mitochondrial and peroxisomal fission. It is tail-anchored to these organelles by a transmembrane domain, exposing a soluble cytoplasmic domain. Previous studies suggested that Fis1 is autoinhibited by its N-terminal region. Here, a 1.75 Å resolution crystal structure of the Fis1 cytoplasmic domain from Saccharomyces cerevisiae is reported which adopts a tetratricopeptide-repeat fold. It is observed that this fold creates a concave surface important for fission, but is sterically occluded by its N-terminal region. Thus, this structure provides a physical basis for autoinhibition and allows a detailed examination of the interactions that stabilize the inhibited state of this molecule

Solution structure of telomere binding domain of AtTRB2 derived from Arabidopsis thaliana

International Nuclear Information System (INIS)

Yun, Ji-Hye; Lee, Won Kyung; Kim, Heeyoun; Kim, Eunhee; Cheong, Chaejoon; Cho, Myeon Haeng; Lee, Weontae

2014-01-01

Highlights: • We have determined solution structure of Myb domain of AtTRB2. • The Myb domain of AtTRB2 is located in the N-terminal region. • The Myb domain of AtTRB2 binds to plant telomeric DNA without fourth helix. • Helix 2 and 3 of the Myb domain of AtTRB2 are involved in DNA recognition. • AtTRB2 is a novel protein distinguished from other known plant TBP. - Abstract: Telomere homeostasis is regulated by telomere-associated proteins, and the Myb domain is well conserved for telomere binding. AtTRB2 is a member of the SMH (Single-Myb-Histone)-like family in Arabidopsis thaliana, having an N-terminal Myb domain, which is responsible for DNA binding. The Myb domain of AtTRB2 contains three α-helices and loops for DNA binding, which is unusual given that other plant telomere-binding proteins have an additional fourth helix that is essential for DNA binding. To understand the structural role for telomeric DNA binding of AtTRB2, we determined the solution structure of the Myb domain of AtTRB2 (AtTRB2 1–64 ) using nuclear magnetic resonance (NMR) spectroscopy. In addition, the inter-molecular interaction between AtTRB2 1–64 and telomeric DNA has been characterized by the electrophoretic mobility shift assay (EMSA) and NMR titration analyses for both plant (TTTAGGG)n and human (TTAGGG)n telomere sequences. Data revealed that Trp28, Arg29, and Val47 residues located in Helix 2 and Helix 3 are crucial for DNA binding, which are well conserved among other plant telomere binding proteins. We concluded that although AtTRB2 is devoid of the additional fourth helix in the Myb-extension domain, it is able to bind to plant telomeric repeat sequences as well as human telomeric repeat sequences

Identification of TTAGGG-binding proteins in Neurospora crassa, a fungus with vertebrate-like telomere repeats.

Science.gov (United States)

Casas-Vila, Núria; Scheibe, Marion; Freiwald, Anja; Kappei, Dennis; Butter, Falk

2015-11-17

To date, telomere research in fungi has mainly focused on Saccharomyces cerevisiae and Schizosaccharomyces pombe, despite the fact that both yeasts have degenerated telomeric repeats in contrast to the canonical TTAGGG motif found in vertebrates and also several other fungi. Using label-free quantitative proteomics, we here investigate the telosome of Neurospora crassa, a fungus with canonical telomeric repeats. We show that at least six of the candidates detected in our screen are direct TTAGGG-repeat binding proteins. While three of the direct interactors (NCU03416 [ncTbf1], NCU01991 [ncTbf2] and NCU02182 [ncTay1]) feature the known myb/homeobox DNA interaction domain also found in the vertebrate telomeric factors, we additionally show that a zinc-finger protein (NCU07846) and two proteins without any annotated DNA-binding domain (NCU02644 and NCU05718) are also direct double-strand TTAGGG binders. We further find two single-strand binders (NCU02404 [ncGbp2] and NCU07735 [ncTcg1]). By quantitative label-free interactomics we identify TTAGGG-binding proteins in Neurospora crassa, suggesting candidates for telomeric factors that are supported by phylogenomic comparison with yeast species. Intriguingly, homologs in yeast species with degenerated telomeric repeats are also TTAGGG-binding proteins, e.g. in S. cerevisiae Tbf1 recognizes the TTAGGG motif found in its subtelomeres. However, there is also a subset of proteins that is not conserved. While a rudimentary core TTAGGG-recognition machinery may be conserved across yeast species, our data suggests Neurospora as an emerging model organism with unique features.

Dissection and Manipulation of LRR Domains in Plant Disease Resistance Gene Products.

Energy Technology Data Exchange (ETDEWEB)

Bent, Andrew [Univ. of Wisconsin, Madison, WI (United States)

2012-11-28

Leucine-rich repeat (LRR) protein domains offer a readily diversifiable platform - literally, an extended protein surface - for specific binding of very diverse ligands. The project addressed the following overlapping research questions: How do leucine-rich repeat proteins recognize their cognate ligands? What are the intra- and inter-molecular transitions that occur that cause transmembrane LRR proteins to switch between off and on states? How do plants use LRR receptor proteins to activate disease resistance? Can we synthetically evolve new LRR proteins that have acquired new ligand specificities?

A role for the malignant brain tumour (MBT domain protein LIN-61 in DNA double-strand break repair by homologous recombination.

Directory of Open Access Journals (Sweden)

Nicholas M Johnson

Full Text Available Malignant brain tumour (MBT domain proteins are transcriptional repressors that function within Polycomb complexes. Some MBT genes are tumour suppressors, but how they prevent tumourigenesis is unknown. The Caenorhabditis elegans MBT protein LIN-61 is a member of the synMuvB chromatin-remodelling proteins that control vulval development. Here we report a new role for LIN-61: it protects the genome by promoting homologous recombination (HR for the repair of DNA double-strand breaks (DSBs. lin-61 mutants manifest numerous problems associated with defective HR in germ and somatic cells but remain proficient in meiotic recombination. They are hypersensitive to ionizing radiation and interstrand crosslinks but not UV light. Using a novel reporter system that monitors repair of a defined DSB in C. elegans somatic cells, we show that LIN-61 contributes to HR. The involvement of this MBT protein in HR raises the possibility that MBT-deficient tumours may also have defective DSB repair.

Regulation of the transient receptor potential channel TRPA1 by its N-terminal ankyrin repeat domain

Czech Academy of Sciences Publication Activity Database

Zayats, Vasilina; Samad, Abdul; Minofar, Babak; Roelofs, K. E.; Stockner, T.; Ettrich, Rüdiger

2012-01-01

Roč. 19, č. 11 (2012), s. 4689-4700 ISSN 1610-2940 R&D Projects: GA ČR GAP207/10/1934 Institutional research plan: CEZ:AV0Z60870520 Keywords : ankyrin repeat * EF-hand * familial episodic pain syndrom * TRPA1 Subject RIV: CE - Biochemistry Impact factor: 1.984, year: 2012

A Role For HR In Corporate Ethics? South African Practitioners’ Perspectives

OpenAIRE

L. J. van Vuuren; R. J. Eiselen

2006-01-01

Since few South African organisations have as yet appointed ethics officers, there is often a lack of clarity on who should take responsibility for coordinating organisations’ ethics management efforts. The purpose of this paper was to assess HR (the Human Resource function and its practitioners) as a possible contender to assume responsibility for ethics management in SA organisations. To this end a mail survey was conducted among registered HR practitioners (N=410). Two factors related to 1...

Limited field investigation report for the 100-HR-3 operable unit

International Nuclear Information System (INIS)

1994-09-01

This limited field investigation (LFI) was conducted to assess the applicability of interim remedial measures (IRM) for reducing human health and environmental risks within the 100-HR-3 Groundwater Operable Unit. The 100-HR-3 Operable Unit is comprised of three subareas; the 100 D Area, the 100 H Area and those portions of the 600 Area between the two reactor areas. The operable unit is one of seven operable units associated with the 100 D and H Areas. Operable units 100-DR-1, 100-DR-2, 100-DR-3, 100-HR-1, 100-HR-2 and 100-IU-4 address contaminant sources while 100-HR-3 addresses contamination present in the underlying groundwater. The primary method of field investigation used during this LFI was the installation and sampling of monitoring wells. Samples were collected from the groundwater and soils, and submitted for laboratory analysis. Boreholes were surveyed for radiological contamination using downhole geophysical techniques to further delineate the locations and levels of contaminants. All samples were screened to ascertain the presence of volatile organic compounds and radionuclides. Analytical data were subjected to validation; all round one, two and three and a minimum of 10% of round four data associated with the LFI were validated. A screening method was used to identify contaminants of potential concern (COPC). This screening method eliminated from further consideration, constituents that were below background. Constituents which are considered non-toxic to humans were eliminated from the human health evaluation. Data consistency and blank contamination were also evaluated in the screening process. These COPC were then evaluated further in the qualitative risk assessment (QRA). A human health QRA was performed using conservative (maximum equilibrated contaminant levels from the LFI) analyses

Leucine-rich repeat kinase-1 regulates osteoclast function by modulating RAC1/Cdc42 Small GTPase phosphorylation and activation.

Science.gov (United States)

Zeng, Canjun; Goodluck, Helen; Qin, Xuezhong; Liu, Bo; Mohan, Subburaman; Xing, Weirong

2016-10-01

Leucine-rich repeat kinase-1 (Lrrk1) consists of ankyrin repeats (ANK), leucine-rich repeats (LRR), a GTPase-like domain of Roc (ROC), a COR domain, a serine/threonine kinase domain (KD), and WD40 repeats (WD40). Previous studies have revealed that knockout (KO) of Lrrk1 in mice causes severe osteopetrosis, and a human mutation of Lrrk1 leads to osteosclerotic metaphysial dysplasia. The molecular mechanism by which Lrrk1 regulates osteoclast function is unknown. In this study, we generated a series of Lrrk1 mutants and evaluated their ability to rescue defective bone resorption in Lrrk1-deficient osteoclasts by use of pit formation assays. Overexpression of Lrrk1 or LRR-truncated Lrrk1, but not ANK-truncated Lrrk1, WD40-truncated Lrrk1, Lrrk1-KD, or K651A mutant Lrrk1, rescued bone resorption function of Lrrk1 KO osteoclasts. We next examined whether RAC1/Cdc42 small GTPases are direct substrates of Lrrk1 in osteoclasts. Western blot and pull-down assays revealed that Lrrk1 deficiency in osteoclasts resulted in reduced phosphorylation and activation of RAC1/Cdc42. In vitro kinase assays confirmed that recombinant Lrrk1 phosphorylated RAC1-GST protein, and immunoprecipitation showed that the interaction of Lrrk1 with RAC1 occurred within 10 min after RANKL treatment. Overexpression of constitutively active Q61L RAC1 partially rescued the resorptive function of Lrrk1-deficient osteoclasts. Furthermore, lack of Lrrk1 in osteoclasts led to reduced autophosphorylation of p21 protein-activated kinase-1 at Ser 144 , catalyzed by RAC1/Cdc42 binding and activation. Our data indicate that Lrrk1 regulates osteoclast function by directly modulating phosphorylation and activation of small GTPase RAC1/Cdc42 and that its function depends on ANK, ROC, WD40, and kinase domains. Copyright © 2016 the American Physiological Society.

Comparative evaluation of heart rate-based monitors: Apple Watch vs Fitbit Charge HR.

Science.gov (United States)

Bai, Yang; Hibbing, Paul; Mantis, Constantine; Welk, Gregory J

2018-08-01

The purpose of this investigation was to examine the validity of energy expenditure (EE), steps, and heart rate measured with the Apple Watch 1 and Fitbit Charge HR. Thirty-nine healthy adults wore the two monitors while completing a semi-structured activity protocol consisting of 20 minutes of sedentary activity, 25 minutes of aerobic exercise, and 25 minutes of light intensity physical activity. Criterion measures were obtained from an Oxycon Mobile for EE, a pedometer for steps, and a Polar heart rate strap worn on the chest for heart rate. For estimating whole-trial EE, the mean absolute percent error (MAPE) from Fitbit Charge HR (32.9%) was more than twice that of Apple Watch 1 (15.2%). This trend was consistent for the individual conditions. Both monitors accurately assessed steps during aerobic activity (MAPE Apple : 6.2%; MAPE Fitbit : 9.4%) but overestimated steps in light physical activity. For heart rate, Fitbit Charge HR produced its smallest MAPE in sedentary behaviors (7.2%), followed by aerobic exercise (8.4%), and light activity (10.1%). The Apple Watch 1 had stronger validity than the Fitbit Charge HR for assessing overall EE and steps during aerobic exercise. The Fitbit Charge HR provided heart rate estimates that were statistically equivalent to Polar monitor.

Interactions between the S-Domain Receptor Kinases and AtPUB-ARM E3 Ubiquitin Ligases Suggest a Conserved Signaling Pathway in Arabidopsis1[W][OA

Science.gov (United States)

Samuel, Marcus A.; Mudgil, Yashwanti; Salt, Jennifer N.; Delmas, Frédéric; Ramachandran, Shaliny; Chilelli, Andrea; Goring, Daphne R.

2008-01-01

The Arabidopsis (Arabidopsis thaliana) genome encompasses multiple receptor kinase families with highly variable extracellular domains. Despite their large numbers, the various ligands and the downstream interacting partners for these kinases have been deciphered only for a few members. One such member, the S-receptor kinase, is known to mediate the self-incompatibility (SI) response in Brassica. S-receptor kinase has been shown to interact and phosphorylate a U-box/ARM-repeat-containing E3 ligase, ARC1, which, in turn, acts as a positive regulator of the SI response. In an effort to identify conserved signaling pathways in Arabidopsis, we performed yeast two-hybrid analyses of various S-domain receptor kinase family members with representative Arabidopsis plant U-box/ARM-repeat (AtPUB-ARM) E3 ligases. The kinase domains from S-domain receptor kinases were found to interact with ARM-repeat domains from AtPUB-ARM proteins. These kinase domains, along with M-locus protein kinase, a positive regulator of SI response, were also able to phosphorylate the ARM-repeat domains in in vitro phosphorylation assays. Subcellular localization patterns were investigated using transient expression assays in tobacco (Nicotiana tabacum) BY-2 cells and changes were detected in the presence of interacting kinases. Finally, potential links to the involvement of these interacting modules to the hormone abscisic acid (ABA) were investigated. Interestingly, AtPUB9 displayed redistribution to the plasma membrane of BY-2 cells when either treated with ABA or coexpressed with the active kinase domain of ARK1. As well, T-DNA insertion mutants for ARK1 and AtPUB9 lines were altered in their ABA sensitivity during germination and acted at or upstream of ABI3, indicating potential involvement of these proteins in ABA responses. PMID:18552232

Can HR practices retain flexworkers with their agency?

NARCIS (Netherlands)

Kroon, B.; Freese, C.

2013-01-01

Purpose Workers have different motives to be employed at specialist contract work agencies, such as career development aspirations, or a desire for freedom and independence. The purpose of this paper is to study how these different motives relate to the appreciation of HR practices applied by

Structural characterization of Mumps virus fusion protein core

International Nuclear Information System (INIS)

Liu Yueyong; Xu Yanhui; Lou Zhiyong; Zhu Jieqing; Hu Xuebo; Gao, George F.; Qiu Bingsheng; Rao Zihe; Tien, Po

2006-01-01

The fusion proteins of enveloped viruses mediating the fusion between the viral and cellular membranes comprise two discontinuous heptad repeat (HR) domains located at the ectodomain of the enveloped glycoproteins. The crystal structure of the fusion protein core of Mumps virus (MuV) was determined at 2.2 A resolution. The complex is a six-helix bundle in which three HR1 peptides form a central highly hydrophobic coiled-coil and three HR2 peptides pack against the hydrophobic grooves on the surface of central coiled-coil in an oblique antiparallel manner. Fusion core of MuV, like those of simian virus 5 and human respiratory syncytium virus, forms typical 3-4-4-4-3 spacing. The similar charecterization in HR1 regions, as well as the existence of O-X-O motif in extended regions of HR2 helix, suggests a basic rule for the formation of the fusion core of viral fusion proteins

The latest on the recent HR staff survey

CERN Multimedia

2009-01-01

The data collected in the framework of the staff survey sent out by the Human Resources (HR) Department in March this year are currently being analysed. The first results concern the response rate and the breakdown of participants. 1328 staff members replied to the questionnaire, representing a response rate of close to 60%. Marie-Luce Falipou, who is in charge of the project within the HR Department, is evidently satisfied with the result: "The high response rate shows that the staff appreciated HR’s efforts to sound out their opinions and felt concerned by the subjects covered in the questionnaire". All the data are now being processed by the team led by Philippe Sarnin, Director of the Social Psychology Department at the University of Lyon2. "The number of responses submitted during the 15 days the form was available on line was very satisfactory. This is a vital factor in ensuring that we are able to build up an accurate pictu...

The effects of multi-domain versus single-domain cognitive training in non-demented older people: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Cheng Yan

2012-03-01

Full Text Available Abstract Background Whether healthy older people can benefit from cognitive training (CogTr remains controversial. This study explored the benefits of CogTr in community dwelling, healthy, older adults and compared the effects of single-domain with multi-domain CogTr interventions. Methods A randomized, controlled, 3-month trial of CogTr with double-blind assessments at baseline and immediate, 6-month and 12-month follow-up after training completion was conducted. A total of 270 healthy Chinese older people, 65 to 75 years old, were recruited from the Ganquan-area community in Shanghai. Participants were randomly assigned to three groups: multi-domain CogTr, single-domain CogTr, and a wait-list control group. Twenty-four sessions of CogTr were administrated to the intervention groups over a three-month period. Six months later, three booster training sessions were offered to 60% of the initial training participants. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Form A, the Color Word Stroop test (CWST, the Visual Reasoning test and the Trail Making test (TMT were used to assess cognitive function. Results Multi-domain CogTr produced statistically significant training effects on RBANS, visual reasoning, and immediate and delayed memory, while single-domain CogTr showed training effects on RBANS, visual reasoning, word interference, and visuospatial/constructional score (all P Conclusions Cognitive training can improve memory, visual reasoning, visuospatial construction, attention and neuropsychological status in community-living older people and can help maintain their functioning over time. Multi-domain CogTr enhanced memory proficiency, while single-domain CogTr augmented visuospatial/constructional and attention abilities. Multi-domain CogTr had more advantages in training effect maintenance. Clinical Trial Registration Chinese Clinical Trial Registry. Registration number: ChiCTR-TRC-09000732.

A Role For HR In Corporate Ethics? South African Practitioners’ Perspectives

Directory of Open Access Journals (Sweden)

L. J. van Vuuren

2006-11-01

Full Text Available Since few South African organisations have as yet appointed ethics officers, there is often a lack of clarity on who should take responsibility for coordinating organisations’ ethics management efforts. The purpose of this paper was to assess HR (the Human Resource function and its practitioners as a possible contender to assume responsibility for ethics management in SA organisations. To this end a mail survey was conducted among registered HR practitioners (N=410. Two factors related to 1 the extent of HR’s ethics management competence and 2 HR’s responsibility for ethics management, were identified. The results showed that HR practitioners on average believe that they indeed have an ethics management competence and that they should be involved in ethics management. However, practitioners with a great deal of exposure to organisations that manage ethics believe to a lesser extent that they should be involved in ethics management. The implications of the findings are discussed.

Structural Basis for Endosomal Targeting by the Bro1 Domain

Science.gov (United States)

Kim, Jaewon; Sitaraman, Sujatha; Hierro, Aitor; Beach, Bridgette M.; Odorizzi, Greg; Hurley, James H.

2010-01-01

Summary Proteins delivered to the lysosome or the yeast vacuole via late endosomes are sorted by the ESCRT complexes and by associated proteins, including Alix and its yeast homolog Bro1. Alix, Bro1, and several other late endosomal proteins share a conserved 160 residue Bro1 domain whose boundaries, structure, and function have not been characterized. The crystal structure of the Bro1 domain of Bro1 reveals a folded core of 367 residues. The extended Bro1 domain is necessary and sufficient for binding to the ESCRT-III subunit Snf7 and for the recruitment of Bro1 to late endosomes. The structure resembles a boomerang with its concave face filled in and contains a triple tetratricopeptide repeat domain as a substructure. Snf7 binds to a conserved hydrophobic patch on Bro1 that is required for protein complex formation and for the protein-sorting function of Bro1. These results define a conserved mechanism whereby Bro1 domain-containing proteins are targeted to endosomes by Snf7 and its orthologs. PMID:15935782

Clinical evaluation of wide-latitude HR-C film for chest radiography

International Nuclear Information System (INIS)

Kim, Young Sung; Hwang, Nam Sun; Yeo, Young Bok; Lee, In Ja; Huh, Joon

1990-01-01

In application of wide latitude HR-C film to chest x-ray examination, former x-ray diagnosis area is larger and diagnostic information has great deal of promotion. HR-C film is compare to former x-ray film is larger latitude and density level is small, reading is very easily. Especially, high estimate that is in characteristic curve linearity of toe part is good, contrast of low density made good shape and not good describe to overlap is diagnostic information increase mediastinum portion etc

Characterization and expression of the maize β-carbonic anhydrase gene repeat regions.

Science.gov (United States)

Tems, Ursula; Burnell, James N

2010-12-01

In maize, carbonic anhydrase (CA; EC 4.2.1.1) catalyzes the first reaction of the C(4) photosynthetic pathway; it catalyzes the hydration of CO(2) to bicarbonate and provides an inorganic carbon source for the primary carboxylation reaction catalyzed by phosphoenolpyruvate (PEP) carboxylase. The β-CA isozymes from maize, as well as other agronomically important NADP-malic enzyme (NADP-ME) type C(4) crops, have remained relatively uncharacterized but differ significantly from the β-CAs of other C(4) monocot species primarily due to transcript length and the presence of repeat sequences. This research confirmed earlier findings of repeat sequences in maize CA transcripts, and demonstrated that the gene encoding these transcripts is also composed of repeat sequences. One of the maize CA genes was sequenced and found to encode two domains, with distinct groups of exons corresponding to the repeat regions of the transcript. We have also shown that expression of a single repeat region of the CA transcript produced active enzyme that associated as a dimer and was composed primarily of α-helices, consistent with that observed for other plant CAs. As the presence of repeat regions in the CA gene is unique to NADP-ME type C(4) monocot species, the implications of these findings in the context of the evolution of the location and function of this C(4) pathway enzyme are strongly suggestive of CA gene duplication resulting in an evolutionary advantage and a higher photosynthetic efficiency. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Employee Work-Life Balance as an HR Imperative | Igbinomwanhia ...

African Journals Online (AJOL)

Employee Work-Life Balance as an HR Imperative. ... With the growing diversity of family structures represented in today‟s workforce, ... of managing an employee's work-life balance have increased markedly over the past 20 years.

Role of endocortical contouring methods on precision of HR-pQCT-derived cortical micro-architecture in postmenopausal women and young adults.

Science.gov (United States)

Kawalilak, C E; Johnston, J D; Cooper, D M L; Olszynski, W P; Kontulainen, S A

2016-02-01

Precision errors of cortical bone micro-architecture from high-resolution peripheral quantitative computed tomography (pQCT) ranged from 1 to 16 % and did not differ between automatic or manually modified endocortical contour methods in postmenopausal women or young adults. In postmenopausal women, manually modified contours led to generally higher cortical bone properties when compared to the automated method. First, the objective of the study was to define in vivo precision errors (coefficient of variation root mean square (CV%RMS)) and least significant change (LSC) for cortical bone micro-architecture using two endocortical contouring methods: automatic (AUTO) and manually modified (MOD) in two groups (postmenopausal women and young adults) from high-resolution pQCT (HR-pQCT) scans. Second, it was to compare precision errors and bone outcomes obtained with both methods within and between groups. Using HR-pQCT, we scanned twice the distal radius and tibia of 34 postmenopausal women (mean age ± SD 74 ± 7 years) and 30 young adults (27 ± 9 years). Cortical micro-architecture was determined using AUTO and MOD contour methods. CV%RMS and LSC were calculated. Repeated measures and multivariate ANOVA were used to compare mean CV% and bone outcomes between the methods within and between the groups. Significance was accepted at P young adults, postmenopausal women had better precision for radial cortical porosity (precision difference 9.3 %) and pore volume (7.5 %) with MOD. Young adults had better precision for cortical thickness (0.8 %, MOD) and tibial cortical density (0.2 %, AUTO). In postmenopausal women, MOD resulted in 0.2-54 % higher values for most cortical outcomes, as well as 6-8 % lower radial and tibial cortical BMD and 2 % lower tibial cortical thickness. Results suggest that AUTO and MOD endocortical contour methods provide comparable repeatability. In postmenopausal women, manual modification of endocortical contours led to

Learning Culture, Line Manager and HR Professional Practice

Science.gov (United States)

Harrison, Patricia

2011-01-01

Purpose: This paper aims to focus on the role of line management and learning culture in the development of professional practice for the human resource (HR) practitioner. Design/methodology/approach: Three-year longitudinal, matched-pair study involving five participants and their line managers. Findings: Two of the five participants experienced…

Engineered bacterial hydrophobic oligopeptide repeats in a synthetic yeast prion, [REP-PSI+

Directory of Open Access Journals (Sweden)

Fátima eGasset-Rosa

2015-04-01

Full Text Available The yeast translation termination factor Sup35p, by aggregating as the [PSI+] prion, enables ribosomes to read-through stop codons, thus expanding the diversity of the Saccharomyces cerevisiae proteome. Yeast prions are functional amyloids that replicate by templating their conformation on native protein molecules, then assembling as large aggregates and fibers. Prions propagate epigenetically from mother to daughter cells by fragmentation of such assemblies. In the N-terminal prion-forming domain, Sup35p has glutamine/asparagine-rich oligopeptide repeats (OPRs, which enable propagation through chaperone-elicited shearing. We have engineered chimeras by replacing the polar OPRs in Sup35p by up to five repeats of a hydrophobic amyloidogenic sequence from the synthetic bacterial prionoid RepA-WH1. The resulting hybrid, [REP-PSI+], i was functional in a stop codon read-through assay in S. cerevisiae; ii generates weak phenotypic variants upon both its expression or transformation into [psi-] cells; iii these variants correlated with high molecular weight aggregates resistant to SDS during electrophoresis; and iv according to fluorescence microscopy, the fusion of the prion domains from the engineered chimeras to the reporter protein mCherry generated perivacuolar aggregate foci in yeast cells. All these are signatures of bona fide yeast prions. As assessed through biophysical approaches, the chimeras assembled as oligomers rather than as the fibers characteristic of [PSI+]. These results suggest that it is the balance between polar and hydrophobic residues in OPRs what determines prion conformational dynamics. In addition, our findings illustrate the feasibility of enabling new propagation traits in yeast prions by engineering OPRs with heterologous amyloidogenic sequence repeats.

Interaction of Prevotella intermedia strain 17 leucine-rich repeat domain protein AdpF with eukaryotic cells promotes bacterial internalization.

Science.gov (United States)

Sengupta, Dipanwita; Kang, Dae-Joong; Anaya-Bergman, Cecilia; Wyant, Tiana; Ghosh, Arnab K; Miyazaki, Hiroshi; Lewis, Janina P

2014-06-01

Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells.

Discussion on the fusing methods for HR and CCD images of CBERS

International Nuclear Information System (INIS)

Gao Zhangsheng; Zhao Yingjun

2010-01-01

CBERS-02B multi-spectral CCD data are different from HR panchromatic data in resolution, which causes difficulty in image fusion. With the method of Pansharping, HPF, Brovey transform, IHS transform, principal component transform, Gram Schmidt (GS) transform and wavelet transform, the authors have tested the fusion methods for CCD data and HR data of CBERS, and the fusion results are discussed and evaluated qualitatively and quantitatively. (authors)

Is the standard dose rate for de-contamination, 0.23 mc-Sv/hr, truly 1 mSv/year?

International Nuclear Information System (INIS)

Furuta, Sadaaki

2014-01-01

Examined is the validity of the standard dose rates in the title, which have been additionally defined by Ministry of the Environment (ME) to the measures of Fukushima Nuclear Power Plant Accident. The standard 0.23 mc-Sv/hr is the sum of natural ambient dose rate 0.04 mc-Sv/hr in average of Japan as measured with NaI scintillation surveymeter, plus additional accidental exposure dose 1 mSv/y, which is defined equivalent to 0.19 mc-Sv/hr. Here, the equation of addition 0.04+0.19 mc-Sv/hr is not exactly correct because the unit of each dose value has different means as follows. The natural dose is derived from the value 5.8 mc-R/hr (0.038 mc-Sv/hr, effective dose) of the average national natural dose data (2011) of Ministry of Education, Culture, Sports, Science and Technology. However, if the measurement is done with the surveymeter which practically gives 1 cm dose equivalent, the rate is calculated to be 0.06 mc-Sv/hr. When the Fukushima prefectural natural dose rate 6.4 mc-R/hr is employed, the calculation gives 0.07 mc-Sv/hr. ME defines the additional doses to be 0.19 mc-Sv/hr and 1 mSv/y, which are derived from the calculation: (0.19 mc-Sv/hr x 8 hr outdoor + 0.19 mc-Sv/hr x 0.4 indoor, shielded) x 365 d/y= 1 mSv/y. The dose is assumed to be measurable with the surveymeter (1 cm dose equivalent) and thereby calculation, if the source is mainly "1"3"4Cs and "1"3"7Cs, gives the effective dose of 0.32 mc-Sv/hr to be managed by the meter. As this, the effective dose unit and 1 cm equivalent dose unit are used for calculation of the administrative standard dose rate of 1 mSv/y, which should be recognized by both radiological experts and administration for the explanation to general public. (T.T.)

Change of offices for HR Department - disrupted service during the last week of February 2013

CERN Multimedia

2013-01-01

HR Department would like to inform that, due to office renovation work, a number of HR Services currently located on the ground, first and second floors of Building 5 will move to temporary offices as from late February.   The removals will take place from Friday 22 until Tuesday 26 February 2013 inclusive and during this period, telephone and e-mail contact may be disrupted. The following services will be relocated to: Building 510  – ground floor (until mid-June) Head of Department and Deputy Office of the Head of HR Department Group Leaders and Partners Diversity Office HR Legal Section Building 652 – Prefab/Algeco (until September) Human Resources Advisors and assistants Staff Recruitment Service Fellows & Apprentices Service Students & Associates Service Temporary office numbers will be available in the CERN phonebook. Any emergencies during the removals may be addressed to Lynda.Leroux@cern.ch Thank you in advance for your understanding. HR Head O...

PENGEMBANGAN PERSAMAAN VO2 MAX DAN EVALUASI HR MAX (STUDI AWAL PADA PEKERJA PRIA

Directory of Open Access Journals (Sweden)

Purnawan Adi Wicaksono

2012-10-01

Full Text Available Kapasitas fisik maksimum seseorang direpresentasikan dengan nilai konsumsi oksigen maksimum (VO2 Max dan denyut nadi maksimum (HR Max yang memberikan suatu informasi batasan kemampuan fisik maksimum seseorang dalam melakukan pekerjaan. Penelitian kali ini mempunyai tujuan untuk mencari nilai VO2 Max pekerja pria Indonesia untuk nantinya akan dikembangkan suatu persamaan prediksi VO2 Max yang didekati dengan hubungan linier antara denyut nadi (Heart Rate seperti yang dilakukan Astrand (2003, tinggi badan (Chatterjee et al, 2006, berat badan (Akalan et al, 2008, usia (Magrani et al, 2009 dan mengevaluasi persamaan HR Max manakah yang dapat diaplikasikan untuk mendekati nilai denyut nadi maksimum pekerja Indonesia. Responden dalam penelitian kali ini adalah 12  pekerja industri pria yang diambil dari beberapa industri di Depok dan sekitarnya. Kriteria responden yang berpartisipasi dalam penelitian kali ini adalah: berusia 20-40 tahun, bukan perokok baik aktif maupun pasif, sehat , tidak mengkonsumsi makanan, kafein, alkohol minimal 2 jam sebelum eksperimen (Balderrama et. al, 2007.Eksperimen yang dilakukan menggunakan metode maximal test dengan protokol treadmill. Adapun peralatan yang digunakan adalah seperangkat alat pengukur kondisi fisiologi Fitmate MED (COSMED srl-Italy terdiri dari Heart Rate Transmitter, Heart Rate Receiver, V mask (Hans Rudolph Inc,dan treadmill SportArt@60.  Eksperimen dilakukan menjadi dua bagian, yaitu istirahat dan tahap bekerja.Aktivitas istirahat terdiri dari tidur selama 20 menit, duduk selama 20 menit dan berdiri selama 10 menit. Eksperimen tahap kedua yaitu tahap kerja yang terdiri dari latihan selama 5 menit. Responden dipersilakan beristirahat selama 15 menit, setelah itu responden melaksanakan maximal test detik hingga responden merasa tidak sanggup lagi melanjutkan eksperimen. Hasil penelitian model prediksi VO2 max untuk pekerja industri pria mempunyai nilai 2,78 ± 0,5 liter/menit dan dengan regresi linier

Elimination of C3 as the Bond-Neff depression opacity source in Hr 774

International Nuclear Information System (INIS)

Baird, S.R.

1982-01-01

The pseudocontinuum of C 3 has been proposed by Fix as the source of the Bond-Neff depression in HR 774. In such a case the strongest rotational lines of the 4050 A vibrational band of C 3 should be clearly evident at high dispersion. A 2.2 A mm -1 plate of HR 774 is examined in the 4050--4060 A region where the strongest lines should form. The absence of C 3 rotational lines indicates that C 3 cannot be the major contributor to the Bond-Neff depression in HR 774

Comparative study of a novel application of automated HR HPV assay and stability in a previously untested Preservative media.

Science.gov (United States)

Morel, Mike E; McBride, Simon E; Gomez, Maria P

2017-12-01

The suitability and stability of cervical cells in Novaprep media (NHQ) for certain HPV assays is unknown. We evaluated the accuracy of an automated HPV assay (Abbott RealTime HR HPV) for cervical cells prepared in NHQ and NHQ with a pre-treatment to mimic a worst case clinical use, compared to the assay manufacturers media; repeatability and reproducibility of HPV results and the stability of detectable HPV in NHQ over time compared to CE marked liquid based cytology preservatives. Cell lines were used to simulate patient samples. Cells stored in NHQ produced accurate, repeatable and reproducible results. Stability in NHQ was comparable to the best performing LBC, with at least 7 months' stability at 18-25°C, 2-8°C, -20°C and -80°C; and at least 3 months' stability at 40°C. Similar results were obtained for pre-treated NHQ except only 3.5 months' stability at 18-25°C. Cell line samples in all media and concentrations tested were detected appropriately by the assay. Based on this first stage validation analytical study, cervical cells stored in NHQ are suitable for the Realtime HPV assay. There should be no reservations for inclusion of NHQ in any further validation and clinical performance evaluation of this assay. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Risk management is every managers’ responsibility: Are HR practitioners ready for the challenge

Directory of Open Access Journals (Sweden)

Pascal Siphelele Zulu

2014-07-01

Full Text Available Risk and Enterprise Risk Management has become a strategic imperative in most organisations and government departments over the years. Most company boards and government entities in South Africa have adopted various corporate governance frameworks as a mechanism to direct and control the operations of their organisations. As a result, risk management and enterprise risk management has become every manager’s responsibility. The key question that the study investigates is whether HR managers are aware of this strategic imperative and ready to be risk champions in their environment. Data was collected from forty eight (48 HR Managers and Practitioners from private companies and sixty eight (68 HR Managers and Practitioners from government departments and government companies in Durban, Kwazulu-Natal and Cape Town, Western Cape using both personal interviews and questionnaires which were distributed to one hundred and fifty (150 employees, of which one hundred and sixteen (116 questionnaires were completed (return rate 77.3%. The results of this paper indicate that, in general and across all sectors, HR practitioners’ levels of understanding of corporate governance and risk management is limited

The Tomato Nucleotide-binding Leucine-rich Repeat Immune Receptor I-2 Couples DNA-binding to Nucleotide-binding Domain Nucleotide Exchange*

Science.gov (United States)

Fenyk, Stepan; Dixon, Christopher H.; Gittens, William H.; Townsend, Philip D.; Sharples, Gary J.; Pålsson, Lars-Olof; Takken, Frank L. W.; Cann, Martin J.

2016-01-01

Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable plants to recognize and respond to pathogen attack. Previously, we demonstrated that the Rx1 NLR of potato is able to bind and bend DNA in vitro. DNA binding in situ requires its genuine activation following pathogen perception. However, it is unknown whether other NLR proteins are also able to bind DNA. Nor is it known how DNA binding relates to the ATPase activity intrinsic to NLR switch function required to immune activation. Here we investigate these issues using a recombinant protein corresponding to the N-terminal coiled-coil and nucleotide-binding domain regions of the I-2 NLR of tomato. Wild type I-2 protein bound nucleic acids with a preference of ssDNA ≈ dsDNA > ssRNA, which is distinct from Rx1. I-2 induced bending and melting of DNA. Notably, ATP enhanced DNA binding relative to ADP in the wild type protein, the null P-loop mutant K207R, and the autoactive mutant S233F. DNA binding was found to activate the intrinsic ATPase activity of I-2. Because DNA binding by I-2 was decreased in the presence of ADP when compared with ATP, a cyclic mechanism emerges; activated ATP-associated I-2 binds to DNA, which enhances ATP hydrolysis, releasing ADP-bound I-2 from the DNA. Thus DNA binding is a general property of at least a subset of NLR proteins, and NLR activation is directly linked to its activity at DNA. PMID:26601946

The Tomato Nucleotide-binding Leucine-rich Repeat Immune Receptor I-2 Couples DNA-binding to Nucleotide-binding Domain Nucleotide Exchange.

Science.gov (United States)

Fenyk, Stepan; Dixon, Christopher H; Gittens, William H; Townsend, Philip D; Sharples, Gary J; Pålsson, Lars-Olof; Takken, Frank L W; Cann, Martin J

2016-01-15

Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable plants to recognize and respond to pathogen attack. Previously, we demonstrated that the Rx1 NLR of potato is able to bind and bend DNA in vitro. DNA binding in situ requires its genuine activation following pathogen perception. However, it is unknown whether other NLR proteins are also able to bind DNA. Nor is it known how DNA binding relates to the ATPase activity intrinsic to NLR switch function required to immune activation. Here we investigate these issues using a recombinant protein corresponding to the N-terminal coiled-coil and nucleotide-binding domain regions of the I-2 NLR of tomato. Wild type I-2 protein bound nucleic acids with a preference of ssDNA ≈ dsDNA > ssRNA, which is distinct from Rx1. I-2 induced bending and melting of DNA. Notably, ATP enhanced DNA binding relative to ADP in the wild type protein, the null P-loop mutant K207R, and the autoactive mutant S233F. DNA binding was found to activate the intrinsic ATPase activity of I-2. Because DNA binding by I-2 was decreased in the presence of ADP when compared with ATP, a cyclic mechanism emerges; activated ATP-associated I-2 binds to DNA, which enhances ATP hydrolysis, releasing ADP-bound I-2 from the DNA. Thus DNA binding is a general property of at least a subset of NLR proteins, and NLR activation is directly linked to its activity at DNA. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Réunion publique HR

CERN Multimedia

CERN. Geneva

2010-01-01

Chers Collègues,Je me permets de vous rappeler qu'une réunion publique organisée par le Département HR se tiendra aujourd'hui:Vendredi 30 avril 2010 à 9h30 dans l'Amphithéâtre principal (café offert dès 9h00).Durant cette réunion, des informations générales seront données sur:le CERN Admin e-guide, qui est un nouveau guide des procédures administratives du CERN ayant pour but de faciliter la recherche d'informations pratiques et d'offrir un format de lecture convivial;le régime d'Assurance Maladie de l'Organisation (présentation effectuée par Philippe Charpentier, Président du CHIS Board) et;la Caisse de Pensions (présentation effectuée par Théodore Economou, Administrateur de la Caisse de Pensions du CERN).Une transmission simultanée de cette réunion sera assur...

Solution structure of telomere binding domain of AtTRB2 derived from Arabidopsis thaliana

Energy Technology Data Exchange (ETDEWEB)

Yun, Ji-Hye [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Won Kyung [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Heeyoun [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Eunhee; Cheong, Chaejoon [Magnetic Resonance Team, Korea Basic Science Institute (KBSI), Ochang, Chungbuk 363-883 (Korea, Republic of); Cho, Myeon Haeng [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Weontae, E-mail: wlee@spin.yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2014-09-26

Highlights: • We have determined solution structure of Myb domain of AtTRB2. • The Myb domain of AtTRB2 is located in the N-terminal region. • The Myb domain of AtTRB2 binds to plant telomeric DNA without fourth helix. • Helix 2 and 3 of the Myb domain of AtTRB2 are involved in DNA recognition. • AtTRB2 is a novel protein distinguished from other known plant TBP. - Abstract: Telomere homeostasis is regulated by telomere-associated proteins, and the Myb domain is well conserved for telomere binding. AtTRB2 is a member of the SMH (Single-Myb-Histone)-like family in Arabidopsis thaliana, having an N-terminal Myb domain, which is responsible for DNA binding. The Myb domain of AtTRB2 contains three α-helices and loops for DNA binding, which is unusual given that other plant telomere-binding proteins have an additional fourth helix that is essential for DNA binding. To understand the structural role for telomeric DNA binding of AtTRB2, we determined the solution structure of the Myb domain of AtTRB2 (AtTRB2{sub 1–64}) using nuclear magnetic resonance (NMR) spectroscopy. In addition, the inter-molecular interaction between AtTRB2{sub 1–64} and telomeric DNA has been characterized by the electrophoretic mobility shift assay (EMSA) and NMR titration analyses for both plant (TTTAGGG)n and human (TTAGGG)n telomere sequences. Data revealed that Trp28, Arg29, and Val47 residues located in Helix 2 and Helix 3 are crucial for DNA binding, which are well conserved among other plant telomere binding proteins. We concluded that although AtTRB2 is devoid of the additional fourth helix in the Myb-extension domain, it is able to bind to plant telomeric repeat sequences as well as human telomeric repeat sequences.

Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor

International Nuclear Information System (INIS)

Fan Shuli; Goto, Kiminobu; Chen Guangchun; Morinaga, Hidetaka; Nomura, Masatoshi; Okabe, Taijiro; Nawata, Hajime; Yanase, Toshihiko

2006-01-01

Previously, we identified a transcriptional coactivator for the activation function-1 (AF-1) domain of the human androgen receptor (AR) and designated it androgen receptor N-terminal domain transactivating protein-1 (ANT-1). This coactivator, which contains multiple tetratricopeptide repeat (TPR) motifs from amino acid (aa) 294, is identical to a component of U5 small nuclear ribonucleoprotein particles and binds specifically to the AR or glucocorticoid receptor. Here, we identified four distinct functional domains. The AR-AF-1-binding domain, which bound to either aa 180-360 or 360-532 in AR-AF-1, clearly overlapped with TAU-1 and TAU-5. This domain and the subnuclear speckle formation domain in ANT-1 were assigned within the TPR motifs, while the transactivating and nuclear localization signal domains resided within the N-terminal sequence. The existence of these functional domains may further support the idea that ANT-1 can function as an AR-AF-1-specific coactivator while mediating a transcription-splicing coupling

Synthetic H-R diagrams as an observational test of stellar evolution theory

International Nuclear Information System (INIS)

Mathews, G.J.; Becker, S.A.; Brunish, W.M.

1983-07-01

Synthetic H-R diagrams are constructed from a grid of stellar models. These are compared directly with observations of young clusters in the LMC and SMC as a test of the models and as a means to determine the age, age dispersion, and composition of the clusters. Significant discrepancies between the observed and model H-R diagrams indicate the possible influences of convective overshoot, large AGB mass-loss rates, and the best value for the mixing length parameter

Exploring high-resolution magic angle spinning (HR-MAS) NMR spectroscopy for metabonomic analysis of apples.

Science.gov (United States)

Vermathen, Martina; Marzorati, Mattia; Vermathen, Peter

2012-01-01

Classical liquid-state high-resolution (HR) NMR spectroscopy has proved a powerful tool in the metabonomic analysis of liquid food samples like fruit juices. In this paper the application of (1)H high-resolution magic angle spinning (HR-MAS) NMR spectroscopy to apple tissue is presented probing its potential for metabonomic studies. The (1)H HR-MAS NMR spectra are discussed in terms of the chemical composition of apple tissue and compared to liquid-state NMR spectra of apple juice. Differences indicate that specific metabolic changes are induced by juice preparation. The feasibility of HR-MAS NMR-based multivariate analysis is demonstrated by a study distinguishing three different apple cultivars by principal component analysis (PCA). Preliminary results are shown from subsequent studies comparing three different cultivation methods by means of PCA and partial least squares discriminant analysis (PLS-DA) of the HR-MAS NMR data. The compounds responsible for discriminating organically grown apples are discussed. Finally, an outlook of our ongoing work is given including a longitudinal study on apples.

Towards Precision Engineering of Canonical Polyketide Synthase Domains: Recent Advances and Future Prospects

Directory of Open Access Journals (Sweden)

Carmen L. Bayly

2017-02-01

Full Text Available Modular polyketide synthases (mPKSs build functionalized polymeric chains, some of which have become blockbuster therapeutics. Organized into repeating clusters (modules of independently-folding domains, these assembly-line-like megasynthases can be engineered by introducing non-native components. However, poor introduction points and incompatible domain combinations can cause both unintended products and dramatically reduced activity. This limits the engineering and combinatorial potential of mPKSs, precluding access to further potential therapeutics. Different regions on a given mPKS domain determine how it interacts both with its substrate and with other domains. Within the assembly line, these interactions are crucial to the proper ordering of reactions and efficient polyketide construction. Achieving control over these domain functions, through precision engineering at key regions, would greatly expand our catalogue of accessible polyketide products. Canonical mPKS domains, given that they are among the most well-characterized, are excellent candidates for such fine-tuning. The current minireview summarizes recent advances in the mechanistic understanding and subsequent precision engineering of canonical mPKS domains, focusing largely on developments in the past year.

Arabidopsis leucine-rich repeat extensin (LRX) proteins modify cell wall composition and influence plant growth.

Science.gov (United States)

Draeger, Christian; Ndinyanka Fabrice, Tohnyui; Gineau, Emilie; Mouille, Grégory; Kuhn, Benjamin M; Moller, Isabel; Abdou, Marie-Therese; Frey, Beat; Pauly, Markus; Bacic, Antony; Ringli, Christoph

2015-06-24

Leucine-rich repeat extensins (LRXs) are extracellular proteins consisting of an N-terminal leucine-rich repeat (LRR) domain and a C-terminal extensin domain containing the typical features of this class of structural hydroxyproline-rich glycoproteins (HRGPs). The LRR domain is likely to bind an interaction partner, whereas the extensin domain has an anchoring function to insolubilize the protein in the cell wall. Based on the analysis of the root hair-expressed LRX1 and LRX2 of Arabidopsis thaliana, LRX proteins are important for cell wall development. The importance of LRX proteins in non-root hair cells and on the structural changes induced by mutations in LRX genes remains elusive. The LRX gene family of Arabidopsis consists of eleven members, of which LRX3, LRX4, and LRX5 are expressed in aerial organs, such as leaves and stem. The importance of these LRX genes for plant development and particularly cell wall formation was investigated. Synergistic effects of mutations with gradually more severe growth retardation phenotypes in double and triple mutants suggest a similar function of the three genes. Analysis of cell wall composition revealed a number of changes to cell wall polysaccharides in the mutants. LRX3, LRX4, and LRX5, and most likely LRX proteins in general, are important for cell wall development. Due to the complexity of changes in cell wall structures in the lrx mutants, the exact function of LRX proteins remains to be determined. The increasingly strong growth-defect phenotypes in double and triple mutants suggests that the LRX proteins have similar functions and that they are important for proper plant development.

In-sourcing HR: shared service centres in the Netherlands

NARCIS (Netherlands)

Farndale, Elaine; Paauwe, Jaap; Hoeksema, Ludwig

2009-01-01

Due to the impact of now widely-available technologies, new logics behind the organisation of the HR function through the in- and outsourcing of HRM activities have been emerging, particularly addressing issues of integration, cost-efficiency and competitive advantage. In particular, increasing

Stimulating teachers’ team performance through team-oriented HR practices

NARCIS (Netherlands)

Bouwmans, Machiel; Runhaar, Piety; Wesselink, Renate; Mulder, Martin

2017-01-01

Teams of teachers are increasingly held accountable for the quality of education and educational reforms in vocational education and training institutions. However, historically teachers have not been required to engage in deep-level collaboration, thus team-oriented HR practices are being used

HR strategy – necessity or fad for business sustainability?

Directory of Open Access Journals (Sweden)

Ghinea Valentina Mihaela

2016-07-01

Full Text Available The present paper pleads for the awareness of HR strategy importance, in terms of proper design and implementation, as they definitely could impede or sustain the development of an organization. By making use of G.VALI, the model of organizational culture dynamics, we look for revealing the impact that (non-existence of HR strategy, its alignment and coherence could have on the organization success. As proven by human experience, all types of strategies could work and be effective in certain conditions. Even more, no one can say that one strategy is better than other. However, in the same way, there is no guarantee of some strategies success. In this light, the difference lays in the handy and clever interlock of the country specific advantages and firm (-tobe specific advantages. For achieving this specific aim, vertical (alignment and horizontal (coherence integration of each functional strategy must be ensured.

HR 8844: A New Transition Object between the Am Stars and the HgMn Stars?

Science.gov (United States)

Monier, R.; Gebran, M.; Royer, F.; Kilicoglu, T.; Frémat, Y.

2018-02-01

While monitoring a sample of apparently slowly rotating superficially normal early-A stars, we have discovered that HR 8844 (A0 V) is actually a new chemically peculiar star. We first compared the high-resolution spectrum of HR 8844 with that of four slow rotators near A0V (ν Cap, ν Cnc, Sirius A, and HD 72660) to highlight similarities and differences. The lines of Ti II, Cr II, Sr II, and Ba II are conspicuous features in the high-resolution high signal-to-noise SOPHIE spectra of HR 8844 and much stronger than in the spectra of the normal star ν Cap. The Hg II line at 3983.93 Å is also present in a 3.5% blend. Selected unblended lines of 31 chemical elements from He up to Hg have been synthesized using model atmospheres computed with ATLAS9 and the spectrum synthesis code SYNSPEC48 including hyperfine structure of various isotopes when relevant. These synthetic spectra have been adjusted to the mean SOPHIE spectrum of HR 8844, and high-resolution spectra of the comparison stars. Chi-squares were minimized to derive abundances or upper limits to the abundances of these elements for HR 8844 and the comparison stars. HR 8844 is found to have underabundances of He, C, O, Mg, Ca, and Sc, mild enhancements of Ti, V, Cr, Mn, and distinct enhancements of the heavy elements Sr, Y, Zr, Ba, La, Pr, Sm, Eu, and Hg, the overabundances increasing steadily with atomic number. This chemical pattern suggests that HR 8844 may actually be a new transition object between the coolest HgMn stars and the Am stars.

The Effect of Caffeine on Repeat-High-Intensity-Effort Performance in Rugby League Players.

Science.gov (United States)

Wellington, Brandon M; Leveritt, Michael D; Kelly, Vincent G

2017-02-01

Repeat-high-intensity efforts (RHIEs) have recently been shown to occur at critical periods of rugby league matches. To examine the effect that caffeine has on RHIE performance in rugby league players. Using a double-blind, placebo-controlled, crossover design, 11 semiprofessional rugby league players (age 19.0 ± 0.5 y, body mass 87.4 ± 12.9 kg, height 178.9 ± 2.6 cm) completed 2 experimental trials that involved completing an RHIE test after either caffeine (300 mg caffeine) or placebo (vitamin H) ingestion. Each trial consisted of 3 sets of 20-m sprints interspersed with bouts of tackling. During the RHIE test, 20-m-sprint time, heart rate (HR), rating of perceived exertion (RPE), and blood lactate were measured. Total time to complete the nine 20-m sprints during the caffeine condition was 1.0% faster (28.46 ± 1.4 s) than during the placebo condition (28.77 ± 1.7 s) (ES = 0.18, 90%CI -0.7 to 0.1 s). This resulted in a very likely chance of caffeine being of benefit to RHIE performance (99% likely to be beneficial). These improvements were more pronounced in the early stages of the test, with a 1.3%, 1.0%, and 0.9% improvement in sprint performance during sets 1, 2, and 3 respectively. There was no significant difference in RPE across the 3 sets (P = .47, 0.48, 1.00) or mean HR (P = .36), maximal HR (P = .74), or blood lactate (P = .50) between treatment conditions. Preexercise ingestion of 300 mg caffeine produced practically meaningful improvements in RHIE performance in rugby league players.

The impact of repeated mismatches in kidney transplantations performed after nonrenal solid organ transplantation.

Science.gov (United States)

Côté, J M; Zhang, X; Dahhou, M; Sapir-Pichhadze, R; Foster, B; Cardinal, H

2018-01-01

The aim of this study was to determine whether kidney transplantations performed after previous nonrenal solid organ transplants are associated with worse graft survival when there are repeated HLA mismatches (RMM) with the previous donor(s). We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients. Our cohort comprised 6624 kidney transplantations performed between January 1, 1990 and January 1, 2015. All patients had previously received 1 or more nonrenal solid organ transplants. RMM were observed in 35.3% of kidney transplantations and 3012 grafts were lost over a median follow-up of 5.4 years. In multivariate Cox regression analyses, we found no association between overall graft survival and either RMM in class 1 (hazard ratio [HR]: 0.97, 95% confidence interval [CI] 0.89-1.07) or class 2 (HR: 0.95, 95% CI 0.85-1.06). Results were similar for the associations between RMM, death-censored graft survival, and patient survival. Our results suggest that the presence of RMM with previous donor(s) does not have an important impact on allograft survival in kidney transplant recipients who have previously received a nonrenal solid organ transplant. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Repeating and non-repeating fast radio bursts from binary neutron star mergers

Science.gov (United States)

Yamasaki, Shotaro; Totani, Tomonori; Kiuchi, Kenta

2018-04-01

Most fast radio bursts (FRB) do not show evidence of repetition, and such non-repeating FRBs may be produced at the time of a merger of binary neutron stars (BNS), provided that the BNS merger rate is close to the high end of the currently possible range. However, the merger environment is polluted by dynamical ejecta, which may prohibit the radio signal from propagating. We examine this by using a general-relativistic simulation of a BNS merger, and show that the ejecta appears about 1 ms after the rotation speed of the merged star becomes the maximum. Therefore there is a time window in which an FRB signal can reach outside, and the short duration of non-repeating FRBs can be explained by screening after ejecta formation. A fraction of BNS mergers may leave a rapidly rotating and stable neutron star, and such objects may be the origin of repeating FRBs like FRB 121102. We show that a merger remnant would appear as a repeating FRB on a time scale of ˜1-10 yr, and expected properties are consistent with the observations of FRB 121102. We construct an FRB rate evolution model that includes these two populations of repeating and non-repeating FRBs from BNS mergers, and show that the detection rate of repeating FRBs relative to non-repeating ones rapidly increases with improving search sensitivity. This may explain why only the repeating FRB 121102 was discovered by the most sensitive FRB search with Arecibo. Several predictions are made, including the appearance of a repeating FRB 1-10 yr after a BNS merger that is localized by gravitational waves and subsequent electromagnetic radiation.

Human Resource Predictive Analytics HRPA For HR Management In Organizations

Directory of Open Access Journals (Sweden)

Sujeet N. Mishra

2015-08-01

Full Text Available Human resource predictive analytics is an evolving application field of analytics for HRM purposes. The purpose of HRM is measuring employee performance and engagement studying workforce collaboration patterns analyzing employee churn and turnover and modelling employee lifetime value. The motive of applying HRPA is to optimize performances and produce better return on investment for organizations through decision making based on data collection HR metrics and predictive models. The paper is divided into three sections to understand the emergence of HR predictive analytics for HRM. Firstly the paper introduces the concept of HRPA. Secondly the paper discusses three aspects of HRPA a Need b Approach amp Application c Impact. Lastly the paper leads to the conclusion on HRPA.

The human 64-kDa polyadenylylation factor contains a ribonucleoprotein-type RNA binding domain and unusual auxiliary motifs

International Nuclear Information System (INIS)

Takagaki, Yoshio; Manley, J.L.; MacDonald, C.C.; Shenk, T.

1992-01-01

Cleavage stimulation factor is one of the multiple factors required for 3'-end cleavage of mammalian pre-mRNAs. The authors have shown previously that this factor is composed of three subunits with estimated molecular masses of 77, 64, and 50 kDa and that the 64-kDa subunit can be UV-cross linked to RNA in a polyadenylylation signal (AAUAAA)-dependent manner. They have now isolated cDNAs encoding the 64-kDa subunit of human cleavage stimulation factor. The 64-kDa subunit contains a ribonucleoprotein-type RNA binding domain in the N-terminal region and a repeat structure in the C-terminal region in which a pentapeptide sequence (consensus MEARA/G) is repeated 12 times and the formation of a long α-helix stabilized by salt bridges is predicted. An ∼270-amino acid segment surrounding this repeat structure is highly enriched in proline and glycine residues (∼20% for each). When cloned 64-kDa subunit was expressed in Escherichia coli, an N-terminal fragment containing the RNA binding domain bound to RNAs in a polyadenylylation-signal-independent manner, suggesting that the RNA binding domain is directly involved in the binding of the 64-kDa subunit to pre-mRNAs

THE CHANGING ROLE OF HR: VALUES AND CONTRIBUTION

DEFF Research Database (Denmark)

Andersen, Torben; Krogager, Per

2011-01-01

This paper illustrates, through a case-study of one of the old life sciences and diagnostics companies in Denmark, Radiometer Medical Plc. (now part of the Danaher Corporation), how the HR-department starts to work in a much more systematic way with effectiveness and efficiency, in the attempt...... with a stronger emphasis on core values and rationalizing the function itself....

The candidate phylum Poribacteria by single-cell genomics: new insights into phylogeny, cell-compartmentation, eukaryote-like repeat proteins, and other genomic features.

Directory of Open Access Journals (Sweden)

Janine Kamke

Full Text Available The candidate phylum Poribacteria is one of the most dominant and widespread members of the microbial communities residing within marine sponges. Cell compartmentalization had been postulated along with their discovery about a decade ago and their phylogenetic association to the Planctomycetes, Verrucomicrobia, Chlamydiae superphylum was proposed soon thereafter. In the present study we revised these features based on genomic data obtained from six poribacterial single cells. We propose that Poribacteria form a distinct monophyletic phylum contiguous to the PVC superphylum together with other candidate phyla. Our genomic analyses supported the possibility of cell compartmentalization in form of bacterial microcompartments. Further analyses of eukaryote-like protein domains stressed the importance of such proteins with features including tetratricopeptide repeats, leucin rich repeats as well as low density lipoproteins receptor repeats, the latter of which are reported here for the first time from a sponge symbiont. Finally, examining the most abundant protein domain family on poribacterial genomes revealed diverse phyH family proteins, some of which may be related to dissolved organic posphorus uptake.

From Admin to Strategy: The Changing Face of the HR Function. IES Report 332.

Science.gov (United States)

Tamkin, Penny; And Others

Evidence from academic research and management experts in the United Kingdom and elsewhere confirms that the recent focus in work organizations on cost reductions through downsizing has changed the roles and structures of many human resources (HR) units. HR units have had to prove their contribution to the organization's bottom line, raise their…

Documentation and localization of force-mediated filamin A domain perturbations in moving cells

Science.gov (United States)

Nakamura, Fumihiko; Song, Mia; Hartwig, John H.; Stossel, Thomas P.

2014-08-01

Endogenously and externally generated mechanical forces influence diverse cellular activities, a phenomenon defined as mechanotransduction. Deformation of protein domains by application of stress, previously documented to alter macromolecular interactions in vitro, could mediate these effects. We engineered a photon-emitting system responsive to unfolding of two repeat domains of the actin filament (F-actin) crosslinker protein filamin A (FLNA) that binds multiple partners involved in cell signalling reactions and validated the system using F-actin networks subjected to myosin-based contraction. Expressed in cultured cells, the sensor-containing FLNA construct reproducibly reported FLNA domain unfolding strikingly localized to dynamic, actively protruding, leading cell edges. The unfolding signal depends upon coherence of F-actin-FLNA networks and is enhanced by stimulating cell contractility. The results establish protein domain distortion as a bona fide mechanism for mechanotransduction in vivo.

Acute effects of Cu on oxygen consumption and 96 hr-LC 50 values ...

African Journals Online (AJOL)

The median lethal copper (Cu) concentration (96 hr-LC50) values for acute Cu toxicity for Tilapia sparrmanii (live mass: 30 ± 8g) in Mooi River hard water of dolomitic origin at 20° C, pH 7.9, was 68.1 µmol l–1. At this 96 hr-LC50 value the specific oxygen consumption rate (∉ O2) decreased by 44.2 (± 2.1) % from a ...

Sequence analyses reveal that a TPR-DP module, surrounded by recombinable flanking introns, could be at the origin of eukaryotic Hop and Hip TPR-DP domains and prokaryotic GerD proteins.

Science.gov (United States)

Hernández Torres, Jorge; Papandreou, Nikolaos; Chomilier, Jacques

2009-05-01

The co-chaperone Hop [heat shock protein (HSP) organising protein] is known to bind both Hsp70 and Hsp90. Hop comprises three repeats of a tetratricopeptide repeat (TPR) domain, each consisting of three TPR motifs. The first and last TPR domains are followed by a domain containing several dipeptide (DP) repeats called the DP domain. These analyses suggest that the hop genes result from successive recombination events of an ancestral TPR-DP module. From a hydrophobic cluster analysis of homologous Hop protein sequences derived from gene families, we can postulate that shifts in the open reading frames are at the origin of the present sequences. Moreover, these shifts can be related to the presence or absence of biological function. We propose to extend the family of Hop co-chaperons into the kingdom of bacteria, as several structurally related genes have been identified by hydrophobic cluster analysis. We also provide evidence of common structural characteristics between hop and hip genes, suggesting a shared precursor of ancestral TPR-DP domains.

Deep thermal infrared imaging of HR 8799 bcde: new atmospheric constraints and limits on a fifth planet

Energy Technology Data Exchange (ETDEWEB)

Currie, Thayne; Cloutier, Ryan; Jayawardhana, Ray [Department of Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, ON M5S 3H4 (Canada); Burrows, Adam [Department of Astrophysical Science, Princeton University, 4 Ivy Lane, Princeton, NJ 08544 (United States); Girard, Julien H. [European Southern Observatory, Alonso de Córdova 3107, Vitacura, Casilla 19001, Santiago (Chile); Fukagawa, Misato [Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 (Japan); Sorahana, Satoko [Department of Astronomy, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kuchner, Marc [Exoplanets and Stellar Astrophysics Laboratory, NASA Goddard Space Flight Center, Code 667, Greenbelt, MD 20771 (United States); Kenyon, Scott J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Madhusudhan, Nikku [Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA (United Kingdom); Itoh, Yoichi [Nishi-Harima Astronomical Observatory, Center for Astronomy, University of Hyago, 407-2 Nishigaichi, Sayo, Hyogo 679-5313 (Japan); Matsumura, Soko [School of Engineering, Physics, and Mathematics, University of Dundee, Dundee DD1 4HN (United Kingdom); Pyo, Tae-Soo [National Astronomical Observatory of Japan, 650 N. Aohoku Place, Hilo, HI 96720 (United States)

2014-11-10

We present new L' (3.8 μm) and Brα (4.05 μm) data and reprocessed archival L' data for the young, planet-hosting star HR 8799 obtained with Keck/NIRC2, VLT/NaCo, and Subaru/IRCS. We detect all four HR 8799 planets in each data set at a moderate to high signal-to-noise ratio (S/N ≳ 6-15). We fail to identify a fifth planet, 'HR 8799 f', at r < 15 AU at a 5σ confidence level: one suggestive, marginally significant residual at 0.''2 is most likely a point-spread function artifact. Assuming companion ages of 30 Myr and the Baraffe planet cooling models, we rule out an HR 8799 f with a mass of 5 M{sub J} (7 M{sub J} ), 7 M{sub J} (10 M{sub J} ), or 12 M{sub J} (13 M{sub J} ) at r {sub proj} ∼ 12 AU, 9 AU, and 5 AU, respectively. All four HR 8799 planets have red early T dwarf-like L' – [4.05] colors, suggesting that their spectral energy distributions peak in between the L' and M' broadband filters. We find no statistically significant difference in HR 8799 cde's color. Atmosphere models assuming thick, patchy clouds appear to better match HR 8799 bcde's photometry than models assuming a uniform cloud layer. While non-equilibrium carbon chemistry is required to explain HR 8799 b and c's photometry/spectra, evidence for it from HR 8799 d and e's photometry is weaker. Future, deep-IR spectroscopy/spectrophotometry with the Gemini Planet Imager, SCExAO/CHARIS, and other facilities may clarify whether the planets are chemically similar or heterogeneous.

Deep thermal infrared imaging of HR 8799 bcde: new atmospheric constraints and limits on a fifth planet

International Nuclear Information System (INIS)

Currie, Thayne; Cloutier, Ryan; Jayawardhana, Ray; Burrows, Adam; Girard, Julien H.; Fukagawa, Misato; Sorahana, Satoko; Kuchner, Marc; Kenyon, Scott J.; Madhusudhan, Nikku; Itoh, Yoichi; Matsumura, Soko; Pyo, Tae-Soo

2014-01-01

We present new L' (3.8 μm) and Brα (4.05 μm) data and reprocessed archival L' data for the young, planet-hosting star HR 8799 obtained with Keck/NIRC2, VLT/NaCo, and Subaru/IRCS. We detect all four HR 8799 planets in each data set at a moderate to high signal-to-noise ratio (S/N ≳ 6-15). We fail to identify a fifth planet, 'HR 8799 f', at r < 15 AU at a 5σ confidence level: one suggestive, marginally significant residual at 0.''2 is most likely a point-spread function artifact. Assuming companion ages of 30 Myr and the Baraffe planet cooling models, we rule out an HR 8799 f with a mass of 5 M J (7 M J ), 7 M J (10 M J ), or 12 M J (13 M J ) at r proj ∼ 12 AU, 9 AU, and 5 AU, respectively. All four HR 8799 planets have red early T dwarf-like L' – [4.05] colors, suggesting that their spectral energy distributions peak in between the L' and M' broadband filters. We find no statistically significant difference in HR 8799 cde's color. Atmosphere models assuming thick, patchy clouds appear to better match HR 8799 bcde's photometry than models assuming a uniform cloud layer. While non-equilibrium carbon chemistry is required to explain HR 8799 b and c's photometry/spectra, evidence for it from HR 8799 d and e's photometry is weaker. Future, deep-IR spectroscopy/spectrophotometry with the Gemini Planet Imager, SCExAO/CHARIS, and other facilities may clarify whether the planets are chemically similar or heterogeneous.

Linking educational leadership styles to the HR architecture for new teachers in primary education.

Science.gov (United States)

Vekeman, Eva; Devos, Geert; Valcke, Martin

2016-01-01

This study aims to gain insight in the relationship between principals' leadership styles and the configuration of different HR practices for new teachers in primary education. Besides the longstanding interest in educational leadership as a key element in teacher and student performance, there is a growing interest in strategic human resource management (SHRM) in the educational sector. However, few educational studies link educational leadership to SHRM. In particular, this study examines the relationship between principals' instructional and transformational leadership style and principals' strategic and HR orientation in configuring HR practices for new teachers. Data were gathered using a mixed methods approach, including interviews with 75 principals as well as an online survey of 1058 teachers in Flemish primary education. Qualitative interview data were transformed and analysed together with the quantitative survey data using logistic regression and ANOVA analyses. The results indicate that both instructional and transformational leadership is associated with the strategic orientation of principals. The HR orientation, on the other hand, is not reflected in the principals' leadership style. Recommendations for further research in this area are discussed.

A Unified Model for Repeating and Non-repeating Fast Radio Bursts

International Nuclear Information System (INIS)

Bagchi, Manjari

2017-01-01

The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

A Unified Model for Repeating and Non-repeating Fast Radio Bursts

Energy Technology Data Exchange (ETDEWEB)

Bagchi, Manjari, E-mail: manjari@imsc.res.in [The Institute of Mathematical Sciences (IMSc-HBNI), 4th Cross Road, CIT Campus, Taramani, Chennai 600113 (India)

2017-04-01

The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

Value-based HR practices, i-deals and clinical error control with CSR as a moderator.

Science.gov (United States)

Luu, Tuan; Rowley, Chris; Siengthai, Sununta; Thanh Thao, Vo

2017-05-08

Purpose Notwithstanding the rising magnitude of system factors in patient safety improvement, "human factors" such as idiosyncratic deals (i-deals) which also contribute to the adjustment of system deficiencies should not be neglected. The purpose of this paper is to investigate the role of value-based HR practices in catalyzing i-deals, which then influence clinical error control. The research further examines the moderating role of corporate social responsibility (CSR) on the effect of value-based HR practices on i-deals. Design/methodology/approach The data were collected from middle-level clinicians from hospitals in the Vietnam context. Findings The research results confirmed the effect chain from value-based HR practices through i-deals to clinical error control with CSR as a moderator. Originality/value The HRM literature is expanded through enlisting i-deals and clinical error control as the outcomes of HR practices.

Repeatability of Cryogenic Multilayer Insulation

Science.gov (United States)

Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

2017-12-01

Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation (MLI) has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five Glenn Research Center (GRC) provided coupons with 25 layers was shown to be +/- 8.4% whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0%. A second group of 10 coupons has been fabricated by Yetispace and tested by Florida State University, the repeatability between coupons has been shown to be +/- 15-25%. Based on detailed statistical analysis, the data has been shown to be statistically significant.

EXCEPTIONAL CLOSURE OF VARIOUS HR DEPARTEMENT SERVICES ON 20 AND 21 SEPTEMBER 2007

CERN Document Server

HR Department

2007-01-01

Due to a group training event, the following services will be exceptionally closed on Thursday 20 and Friday 21 September 2007 : installation service (removals, cars, diplomatic privileges), school fees, Personnel Records Office (including attestations), French visas; duty travel, leave, reinstallation indemnity, unemployment benefit, tax information and social affairs. The French and Swiss cards service will remain open as usual, from 8:30 to 12:30. Thank you for your understanding. HR Department HR-SPS Group

EXCEPTIONAL CLOSURE OF VARIOUS HR DEPARTMENT SERVICES ON 20 AND 21 SEPTEMBER 2007

CERN Document Server

*Beyond was established as CIC Productions to produce the television series Beyond 2000 for the Seven Network in Australia,

2007-01-01

Due to a group training event, the following services will be exceptionally closed on Thursday 20 and Friday 21 September 2007: installation service (removals, cars, diplomatic privileges), school fees, Personnel Records Office (including attestations), French visas; duty travel, leave, reinstallation indemnity, unemployment benefit, tax information and social affairs. The French and Swiss cards service will remain open as usual, from 8:30 to 12:30. Thank you for your understanding. HR Department HR-SPS Group

Asymmetry of inverted-topology repeats in the AE1 anion exchanger suggests an elevator-like mechanism

Science.gov (United States)

Faraldo-Gómez, José D.

2017-01-01

The membrane transporter anion exchanger 1 (AE1), or band 3, is a key component in the processes of carbon-dioxide transport in the blood and urinary acidification in the renal collecting duct. In both erythrocytes and the basolateral membrane of the collecting-duct α-intercalated cells, the role of AE1 is to catalyze a one-for-one exchange of chloride for bicarbonate. After decades of biochemical and functional studies, the structure of the transmembrane region of AE1, which catalyzes the anion-exchange reaction, has finally been determined. Each protomer of the AE1 dimer comprises two repeats with inverted transmembrane topologies, but the structures of these repeats differ. This asymmetry causes the putative substrate-binding site to be exposed only to the extracellular space, consistent with the expectation that anion exchange occurs via an alternating-access mechanism. Here, we hypothesize that the unknown, inward-facing conformation results from inversion of this asymmetry, and we propose a model of this state constructed using repeat-swap homology modeling. By comparing this inward-facing model with the outward-facing experimental structure, we predict that the mechanism of AE1 involves an elevator-like motion of the substrate-binding domain relative to the nearly stationary dimerization domain and to the membrane plane. This hypothesis is in qualitative agreement with a wide range of biochemical and functional data, which we review in detail, and suggests new avenues of experimentation. PMID:29167180

Asymmetry of inverted-topology repeats in the AE1 anion exchanger suggests an elevator-like mechanism.

Science.gov (United States)

Ficici, Emel; Faraldo-Gómez, José D; Jennings, Michael L; Forrest, Lucy R

2017-12-04

The membrane transporter anion exchanger 1 (AE1), or band 3, is a key component in the processes of carbon-dioxide transport in the blood and urinary acidification in the renal collecting duct. In both erythrocytes and the basolateral membrane of the collecting-duct α-intercalated cells, the role of AE1 is to catalyze a one-for-one exchange of chloride for bicarbonate. After decades of biochemical and functional studies, the structure of the transmembrane region of AE1, which catalyzes the anion-exchange reaction, has finally been determined. Each protomer of the AE1 dimer comprises two repeats with inverted transmembrane topologies, but the structures of these repeats differ. This asymmetry causes the putative substrate-binding site to be exposed only to the extracellular space, consistent with the expectation that anion exchange occurs via an alternating-access mechanism. Here, we hypothesize that the unknown, inward-facing conformation results from inversion of this asymmetry, and we propose a model of this state constructed using repeat-swap homology modeling. By comparing this inward-facing model with the outward-facing experimental structure, we predict that the mechanism of AE1 involves an elevator-like motion of the substrate-binding domain relative to the nearly stationary dimerization domain and to the membrane plane. This hypothesis is in qualitative agreement with a wide range of biochemical and functional data, which we review in detail, and suggests new avenues of experimentation. © 2017 Ficici et al.

Structural Determinants at the Interface of the ARC2 and LRR Domains Control the Activation of the NB-LRR Plant Immune Receptors Rx1 and Gpa2

NARCIS (Netherlands)

Slootweg, E.J.; Spiridon, L.N.; Roosien, J.; Butterbach, P.B.E.; Pomp, H.; Westerhof, L.B.; Wilbers, R.H.P.; Bakker, E.H.; Bakker, J.; Petrescu, A.J.; Smant, G.; Goverse, A.

2013-01-01

Many plant and animal immune receptors have a modular NB-LRR architecture in which a nucleotide-binding switch domain (NB-ARC) is tethered to a leucine-rich repeat sensor domain (LRR). The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly

Understanding the effectiveness of precursor reductions in lowering 8-hr ozone concentrations--Part II. The eastern United States.

Science.gov (United States)

Reynolds, Steven D; Blanchard, Charles L; Ziman, Stephen D

2004-11-01

Analyses of ozone (O3) measurements in conjunction with photochemical modeling were used to assess the feasibility of attaining the federal 8-hr O3 standard in the eastern United States. Various combinations of volatile organic compound (VOC) and oxides of nitrogen (NOx) emission reductions were effective in lowering modeled peak 1-hr O3 concentrations. VOC emissions reductions alone had only a modest impact on modeled peak 8-hr O3 concentrations. Anthropogenic NOx emissions reductions of 46-86% of 1996 base case values were needed to reach the level of the 8-hr standard in some areas. As NOx emissions are reduced, O3 production efficiency increases, which accounts for the less than proportional response of calculated 8-hr O3 levels. Such increases in O3 production efficiency also were noted in previous modeling work for central California. O3 production in some urban core areas, such as New York City and Chicago, IL, was found to be VOC-limited. In these areas, moderate NOx emissions reductions may be accompanied by increases in peak 8-hr O3 levels. The findings help to explain differences in historical trends in 1- and 8-hr O3 levels and have serious implications for the feasibility of attaining the 8-hr O3 standard in several areas of the eastern United States.

Limited field investigation report for the 100-HR-2 Operable Unit

International Nuclear Information System (INIS)

1994-09-01

This report summarizes the data collection and analysis activities conducted during the 100-HR-2 Operable Unit investigative phase and the associated qualitative risk assessment (QRA). The 100-HR-2 Operable Unit contains solid waste burial grounds, an ash pit, bum pits, electrical facilities, septic systems, and support facilities. All known and suspected areas of contamination were classified as solid waste burial grounds or low-priority waste sites based on the collective knowledge of the operable unit managers (representatives from the US Department of Energy [DOE], the US Environmental Protection Agency [EPA], and Washington Department of Ecology [Ecology]) during the preparation of the 100-HR-2 Operable Unit work plan (DOE/RL 1993f). Solid waste burial grounds were judged to pose sufficient risk(s), through one or more pathways, to require evaluation for an interim remedial measure (IRM) as per the Hanford Past-Practice Strategy (HPPS) (DOE/RL 1991) and negotiations with DOE, EPA, and Ecology. An IRM is intended to achieve remedies that are likely to lead to a final record of decision. Low-priority sites are those judged not to pose significant risk to require the streamlined evaluation. There were six low-priority waste sites and seven solid waste burial grounds identified. The investigative phase was conducted in accordance with the RCRA Facility Investigation/Corrective Measures Study Work Plan for the 100-HR-2 Operable Unit (DOE/RL 1993f). The QRA was performed in accordance with the Hanford Site Baseline Risk Assessment Methodology (DOE/RL 1993b) and the recommendations incorporate the strategies of the HPPS. The purpose of this report is to: (1) provide a summary of site investigative activities; (2) refine the conceptual exposure model (as needed); (3) identify chemical- and location-specific corrective action requirements; and (4) provide a human health and ecological QRA associated with solid waste burial grounds

Implementation HR information system – part of a unified information environment of MPEI

Directory of Open Access Journals (Sweden)

I. M. Krepkov

2016-01-01

Full Text Available The article is devoted to the unified information environment of National Research University “Moscow Power Engineering Institute” (MPEI, and its most important component – the HR information system. The article describes the architecture of the unified information space of MPEI. The main objective of the development of the HR information system – to provide access to users, including other information systems, to actual information about employees of MPEI.HR information system are based on many years of operating experience of the previous system and the like, are available on the market today, taking into account the decisions of personnel. The earlier HR information system was developed in 1995–1997 and used until mid-2015. In the process of its using it has accumulated a large number of «patches» and requests for revision that was stopped by limitations in the platform and solutions architecture. Comparative analysis of 1C and SAP products showed that the cost of implementation, configuration and maintenance of these products is higher than developing new solutions. Package of Microsoft technology software was chosen as a platform. These technologies have proven themselves in the development of similar projects, and vendor solutions for a long time support all key processes of information systems. Important is the presence of the selected software Microsoft FSTEC certificates (Federal Service for Technical and Export Control, which support the use of these products for storing and processing information in accordance with the laws of the Russian Federation. The MPEI has already implemented a number of systems on the Microsoft platform – postgraduate register, an Internet portal, etc. The use of technology of one supplier facilitates the integration processes and products into a unified information environment. The article details the technical and hardware specifications of the HR information system. The result of the work on

How the impact of HR practices on employee well-being and performance changes with age

NARCIS (Netherlands)

Kooij, T.A.M.; Guest, D.; Clinton, M.; Knight, T.; Jansen, P.G.W.; Dikkers, J.S.E.

2013-01-01

With changing retirement ages and an aging workforce, interest is growing on the potential contribution of relevant bundles of HR practices in eliciting well-being and performance among aging workers. Drawing on theories on lifespan development and self-regulation, we distinguished two bundles of HR

How the impact of HR Practices on employee well-being and performance changes with age

NARCIS (Netherlands)

Kooij, T.A.M.; Guest, D.; Clinton, M.; Knight, T.; Jansen, P.G.W.; Dikkers, J.S.E.

2013-01-01

With changing retirement ages and an aging workforce, interest is growing on the potential contribution of relevant bundles of HR practices in eliciting well-being and performance among aging workers. Drawing on theories on lifespan development and self-regulation, we distinguished two bundles of HR

[THE FIRST EPIDEMIOLOGICAL DATA ABOUT THE HR-HUMAN PAPILLOMA VIRUS TYPES IN SOUTH AND NORTHERN BULGARIA].

Science.gov (United States)

Kovachev, S; Slavov, V; Slavova, K; Ganovska, A

2015-01-01

The aim of our study were to evaluate the prevalence of HR-HPV infection in women between 15 and 55 years of age in the South and Northern Bulgaria. We have analyzed the HPV status (using DNA-sorb-AM nucleic acid extraction kit) in cervical samples collected during a 3 year period (2010-2012) from 1020 women, aged 15-55 and divided in four age groups, who attended their gynecologists for HPV-DNA cervical test. The rate of the HR-HPV infection was established to be 39.9%. HR-HPV negative were 60.1% of the evaluated subjects. The most commonly isolated genotype in all 407 (100%) infected women was HPV 16 - 190 women (46.7%), followed by HPV 56 - 78 (19.1%), HPV 31- 48 (11.8%) and HPV 33 - 45 (11.1%). To our knowledge, this is the first survey evaluating the prevalence of HR-HPV infection in the South and Northern regions of Bulgarian towns and drawing attention to the unusually high proportion of different HR-HPV.

Deployment Repeatability

Science.gov (United States)

2016-04-01

evaluating the deployment repeatability builds upon the testing or analysis of deployment kinematics (Chapter 6) and adds repetition. Introduction...material yield or failure during a test. For the purposes of this chapter, zero shift will refer to permanent changes in the structure, while reversible ...the content of other chapters in this book: Gravity Compensation (Chapter 4) and Deployment Kinematics and Dynamics (Chapter 6). Repeating the

Src binds cortactin through an SH2 domain cystine-mediated linkage

Science.gov (United States)

Evans, Jason V.; Ammer, Amanda G.; Jett, John E.; Bolcato, Chris A.; Breaux, Jason C.; Martin, Karen H.; Culp, Mark V.; Gannett, Peter M.; Weed, Scott A.

2012-01-01

Summary Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions. PMID:23097045

Src binds cortactin through an SH2 domain cystine-mediated linkage.

Science.gov (United States)

Evans, Jason V; Ammer, Amanda G; Jett, John E; Bolcato, Chris A; Breaux, Jason C; Martin, Karen H; Culp, Mark V; Gannett, Peter M; Weed, Scott A

2012-12-15

Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions.

Mutations in the FHA-domain of ectopically expressed NBS1 lead to radiosensitization and to no increase in somatic mutation rates via a partial suppression of homologous recombination

International Nuclear Information System (INIS)

Ohara, Maki; Funyu, Yumi; Ebara, Shunsuke

2014-01-01

Ionizing radiation induces DNA double-strand breaks (DSBs). Mammalian cells repair DSBs through multiple pathways, and the repair pathway that is utilized may affect cellular radiation sensitivity. In this study, we examined effects on cellular radiosensitivity resulting from functional alterations in homologous recombination (HR). HR was inhibited by overexpression of the forkhead-associated (FHA) domain-mutated NBS1 (G27D/R28D: FHA-2D) protein in HeLa cells or in hamster cells carrying a human X-chromosome. Cells expressing FHA-2D presented partially (but significantly) HR-deficient phenotypes, which were assayed by the reduction of gene conversion frequencies measured with a reporter assay, a decrease in radiation-induced Mre11 foci formation, and hypersensitivity to camptothecin treatments. Interestingly, ectopic expression of FHA-2D did not increase the frequency of radiation-induced somatic mutations at the HPRT locus, suggesting that a partial reduction of HR efficiency has only a slight effect on genomic stability. The expression of FHA-2D rendered the exponentially growing cell population slightly (but significantly) more sensitive to ionizing radiation. This radiosensitization effect due to the expression of FHA-2D was enhanced when the cells were irradiated with split doses delivered at 24-h intervals. Furthermore, enhancement of radiation sensitivity by split dose irradiation was not seen in contact-inhibited G0/G1 populations, even though the cells expressed FHA-2D. These results suggest that the FHA domain of NBS1 might be an effective molecular target that can be used to induce radiosensitization using low molecular weight chemicals, and that partial inhibition of HR might improve the effectiveness of cancer radiotherapy. (author)

Patient-reported Quality of Life and Treatment Satisfaction in Patients With HR+/HER2- Advanced/Metastatic Breast Cancer.

Science.gov (United States)

Wood, Robert; Mitra, Debanjali; de Courcy, Jonathan; Iyer, Shrividya

2017-08-01

Social/Family Well-Being and Functional Well-Being domains of the Functional Assessment of Cancer Therapy-Breast. Patients with bone and visceral metastases had significantly greater concerns about treatment side effects than those with metastases at other sites. Receipt of a greater number of prior lines of therapy was associated with poorer well-being scores. There was a significant negative association between number of lines of treatment and treatment expectations. Findings from this study from clinical practice suggest that treatment outcomes in HR + /HER2 - ABC/MBC could be optimized through improved understanding of the impact that components of patient care have on health-related quality of life and treatment satisfaction. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

A conserved domain in type III secretion links the cytoplasmic domain of InvA to elements of the basal body

International Nuclear Information System (INIS)

Lilic, Mirjana; Quezada, Cindy M.; Stebbins, C. Erec

2010-01-01

The cytoplasmic domain of Salmonella InvA shares homology to a recurring scaffold in the membrane-spanning components of the type II and type III secretion systems. Protein type III secretion systems (T3SSs) are organic nanosyringes that achieve an energy-dependent translocation of bacterial proteins through the two membranes of Gram-negative organisms. Examples include the pathogenic systems of animals, plants and symbiotic bacteria that inject factors into eukaryotic cells, and the flagellar export system that secretes flagellin. T3SSs possess a core of several membrane-associated proteins that are conserved across all known bacterial species that use this system. The Salmonella protein InvA is one of the most highly conserved proteins of this core of critical T3SS components. The crystal structure of a C-terminal domain of InvA reveals an unexpected homology to domains that have been repeatedly found as building blocks of other elements of the T3SS apparatus. This suggests the surprising hypothesis that evolution has produced a significant component of the apparatus structure through a series of gene-duplication and gene-rearrangement events

A Qualitative Study of HR/OHS Stress Interventions in Australian Universities

Science.gov (United States)

Winefield, Anthony H.; Boyd, Carolyn M.

2018-01-01

To enhance the understanding of psychosocial factors and extend research on work stress interventions, we investigated the key human resource (HR)/occupational health and safety (OHS) stress interventions implemented at five Australian universities over a three-year period. Five senior HR Directors completed an online survey to identify the intervention strategies taken at their university in order to reduce stress and enhance employee well-being and morale. We also explored the types of individual-, organization-, and individual/organization-directed interventions that were implemented, and the strategies that were prioritized at each university. Across universities, the dominant interventions were strategies that aimed to balance the social exchange in the work contract between employee-organization with an emphasis on initiatives to: enhance training, career development and promotional opportunities; improve remuneration and recognition practices; and to enhance the fairness of organizational policies and procedures. Strategies to improve work-life balance were also prominent. The interventions implemented were predominantly proactive (primary) strategies focused at the organizational level and aimed at eliminating or reducing or altering work stressors. The findings contribute to the improved management of people at work by identifying university-specific HR/OHS initiatives, specifically leadership development and management skills programs which were identified as priorities at three universities. PMID:29315278

A Qualitative Study of HR/OHS Stress Interventions in Australian Universities.

Science.gov (United States)

Pignata, Silvia; Winefield, Anthony H; Boyd, Carolyn M; Provis, Chris

2018-01-09

To enhance the understanding of psychosocial factors and extend research on work stress interventions, we investigated the key human resource (HR)/occupational health and safety (OHS) stress interventions implemented at five Australian universities over a three-year period. Five senior HR Directors completed an online survey to identify the intervention strategies taken at their university in order to reduce stress and enhance employee well-being and morale. We also explored the types of individual-, organization-, and individual/organization-directed interventions that were implemented, and the strategies that were prioritized at each university. Across universities, the dominant interventions were strategies that aimed to balance the social exchange in the work contract between employee-organization with an emphasis on initiatives to: enhance training, career development and promotional opportunities; improve remuneration and recognition practices; and to enhance the fairness of organizational policies and procedures. Strategies to improve work-life balance were also prominent. The interventions implemented were predominantly proactive (primary) strategies focused at the organizational level and aimed at eliminating or reducing or altering work stressors. The findings contribute to the improved management of people at work by identifying university-specific HR/OHS initiatives, specifically leadership development and management skills programs which were identified as priorities at three universities.

A Qualitative Study of HR/OHS Stress Interventions in Australian Universities

Directory of Open Access Journals (Sweden)

Silvia Pignata

2018-01-01

Full Text Available To enhance the understanding of psychosocial factors and extend research on work stress interventions, we investigated the key human resource (HR/occupational health and safety (OHS stress interventions implemented at five Australian universities over a three-year period. Five senior HR Directors completed an online survey to identify the intervention strategies taken at their university in order to reduce stress and enhance employee well-being and morale. We also explored the types of individual-, organization-, and individual/organization-directed interventions that were implemented, and the strategies that were prioritized at each university. Across universities, the dominant interventions were strategies that aimed to balance the social exchange in the work contract between employee-organization with an emphasis on initiatives to: enhance training, career development and promotional opportunities; improve remuneration and recognition practices; and to enhance the fairness of organizational policies and procedures. Strategies to improve work-life balance were also prominent. The interventions implemented were predominantly proactive (primary strategies focused at the organizational level and aimed at eliminating or reducing or altering work stressors. The findings contribute to the improved management of people at work by identifying university-specific HR/OHS initiatives, specifically leadership development and management skills programs which were identified as priorities at three universities.

Reconfigurable multiport EPON repeater

Science.gov (United States)

Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

2009-11-01

An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

Direct detection and orbital analysis of the exoplanets HR 8799 bcd from archival 2005 Keck/NIRC2 data

NARCIS (Netherlands)

Currie, T.; Fukagawa, M.; Thalmann, C.; Matsumura, S.; Plavchan, P.

2012-01-01

We present previously unpublished 2005 July H-band coronagraphic data of the young, planet-hosting star HR 8799 from the newly released Keck/NIRC2 archive. Despite poor observing conditions, we detect three of the planets (HR 8799 bcd), two of them (HR 8799 bc) without advanced image processing.

100-HR-2 Operable Unit Focused Feasibility study report

International Nuclear Information System (INIS)

1995-01-01

The standard Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) Feasibility Study (FS) includes development and screening of alternatives (Phases 1 and 2) and the detailed analysis of alternatives (Phase 3). This focused feasibility study (FFS) was conducted for the 100-HR-2 Operable Unit (OU) at the Hanford Site in southeastern Washington. This FFS constitutes the Phase 3 portion of the FS process for the remedial alternatives initially developed and screened in the 100 Area Feasibility Study Phases 1 and 2 (DOE-RL 1993a). The objective of this OU-specific FFS is to provide decision makers with sufficient information to allow appropriate and timely selection of interim remedial measures (IRM) for the seven IRM candidate sites associated with the 100-HR-2 OU. The IRM candidate waste sites identified in Table ES-1 are determined in the limited field investigation (DOE-RL 1994b). Site profiles are developed for each of these waste sites. The site profiles are used in the application of the plug-in approach. The waste site either plugs into the analysis of the alternatives for the group, or deviations from the developed group alternatives are described and documented. A summary for the 100-HR-2 IRM candidate waste site is as follows: none of the waste sites require additional alternative development. six of the seven waste sites directly plug into the waste site group alternatives. The site-specific detailed analysis is conducted, referencing the waste site group analysis as appropriate. A waste site detailed analysis summary is presented in Table ES-1.A comparative analysis of remedial alternatives is presented for each waste site. A summary of the comparative analysis is presented in Table ES-2

Oral streptococci utilize a Siglec-like domain of serine-rich repeat adhesins to preferentially target platelet sialoglycans in human blood.

Directory of Open Access Journals (Sweden)

Lingquan Deng

2014-12-01

Full Text Available Damaged cardiac valves attract blood-borne bacteria, and infective endocarditis is often caused by viridans group streptococci. While such bacteria use multiple adhesins to maintain their normal oral commensal state, recognition of platelet sialoglycans provides an intermediary for binding to damaged valvular endocardium. We use a customized sialoglycan microarray to explore the varied binding properties of phylogenetically related serine-rich repeat adhesins, the GspB, Hsa, and SrpA homologs from Streptococcus gordonii and Streptococcus sanguinis species, which belong to a highly conserved family of glycoproteins that contribute to virulence for a broad range of Gram-positive pathogens. Binding profiles of recombinant soluble homologs containing novel sialic acid-recognizing Siglec-like domains correlate well with binding of corresponding whole bacteria to arrays. These bacteria show multiple modes of glycan, protein, or divalent cation-dependent binding to synthetic glycoconjugates and isolated glycoproteins in vitro. However, endogenous asialoglycan-recognizing clearance receptors are known to ensure that only fully sialylated glycans dominate in the endovascular system, wherein we find these particular streptococci become primarily dependent on their Siglec-like adhesins for glycan-mediated recognition events. Remarkably, despite an excess of alternate sialoglycan ligands in cellular and soluble blood components, these adhesins selectively target intact bacteria to sialylated ligands on platelets, within human whole blood. These preferred interactions are inhibited by corresponding recombinant soluble adhesins, which also preferentially recognize platelets. Our data indicate that circulating platelets may act as inadvertent Trojan horse carriers of oral streptococci to the site of damaged endocardium, and provide an explanation why it is that among innumerable microbes that gain occasional access to the bloodstream, certain viridans group

Next HR Department Public meeting

CERN Multimedia

2012-01-01

  Dear Colleagues, I am pleased to invite you to the next public meeting organized by HR Department, which will take place on Monday 25 June at 14:30, for the first time in the Globe (in front of the Reception). The agenda will comprise of: ·         the recent staff member survey results ·         the Diversity at CERN ·         the Learning and Development Policy The first topic concerns, more specifically, staff members. All presentations will be made in English, however, we are pleased to inform you that a simultaneous interpretation in French is foreseen. Should you not be able to attend the meeting, it can also be followed via Webcast and the recording will be made available on Indico. Finally, subject to a favourable weather, refreshments...

The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator

DEFF Research Database (Denmark)

Behrendt, N; Ploug, M; Patthy, L

1991-01-01

with the internal repeats of u-PAR constitute the extracellular part of Ly-6 antigens and of the squid glycoprotein Sgp-2. Like u-PAR, these proteins are attached to the membrane by a glycosyl-phosphatidylinositol anchor. The hydrophilic, ligand-binding u-PAR domain identified in the present study has potential...

Reducing employees’ turnover intention through Hr-induced organizational citizenship behaviour: Leader-member exchange as the mediator

Directory of Open Access Journals (Sweden)

YU GHEE WEE

2013-07-01

Full Text Available This study examines the possibility of inducing organizational citizenship behavior (OCB through human resource (HR philosophy and high involvement HR practices administered at the workplace. Leader-member exchange (LMX, a basis of relational infrastructure, is posited to be a potential mediator. Data was collected from hotel frontline employees, tested and analyzed through structural equation modeling. Findings show that HR philosophy drives the formulation of the bundles of high involvement human resource practices and such philosophy contribute to employees’ willingness in exhibiting organizational citizenship behavior (OCB directed at individuals (OCBI as well as organizations (OCBO as a whole. High involvement HR practices, however, do not elicit OCB but these practices are significantly related to LMX, a new theoretical insight which should invite future research. Although exchanges between supervisors and subordinates are shown to have influences on employees’ willingness in performing OCB, LMX does not, however, mediate the relationship between high involvement HR practices and OCB. Overall, hotel frontline employees participated in this study exhibit more OCBO, rather than OCBI; and such behavior reduce their intention to leave. Both theoretical and practical implications as well as avenues for future research are discussed.

Sequence analyses reveal that a TPR–DP module, surrounded by recombinable flanking introns, could be at the origin of eukaryotic Hop and Hip TPR–DP domains and prokaryotic GerD proteins

Science.gov (United States)

Papandreou, Nikolaos; Chomilier, Jacques

2008-01-01

The co-chaperone Hop [heat shock protein (HSP) organising protein] is known to bind both Hsp70 and Hsp90. Hop comprises three repeats of a tetratricopeptide repeat (TPR) domain, each consisting of three TPR motifs. The first and last TPR domains are followed by a domain containing several dipeptide (DP) repeats called the DP domain. These analyses suggest that the hop genes result from successive recombination events of an ancestral TPR–DP module. From a hydrophobic cluster analysis of homologous Hop protein sequences derived from gene families, we can postulate that shifts in the open reading frames are at the origin of the present sequences. Moreover, these shifts can be related to the presence or absence of biological function. We propose to extend the family of Hop co-chaperons into the kingdom of bacteria, as several structurally related genes have been identified by hydrophobic cluster analysis. We also provide evidence of common structural characteristics between hop and hip genes, suggesting a shared precursor of ancestral TPR–DP domains. Electronic supplementary material The online version of this article (doi:10.1007/s12192-008-0083-8) contains supplementary material, which is available to authorized users. PMID:18987995

High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology

Science.gov (United States)

Rijkaart, D. C.; Heideman, D. A. M.; Coupe, V. M. H.; Brink, A. A. T. P.; Verheijen, R. H. M.; Skomedal, H.; Karlsen, F.; Morland, E.; Snijders, P. J. F.

2012-01-01

Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy. PMID:22553244

The Plant Leucine-Rich Repeat Receptor-Like Kinase PSY1R from Head to Toe

DEFF Research Database (Denmark)

Oehlenschlæger, Christian Berg

PSY1R belongs to the family of plant leucine-rich repeat receptor-like kinases that play important roles in processes such as growth regulation and plant immunity response. PSY1R was proposed to be the receptor of the plant peptide hormone PSY1 which promotes cell expansion. PSY1R was furthermore...... is activated. This work provides the first study of the direct interaction between PSY1R and the peptide ligand PSY1. The binding was evaluated both for full length PSY1R expressed in plants and for the isolated extracellular domain expressed in insect cells. PSY1 binds to the extracellular domain of PSY1R...... shown to phosphorylate and regulate the activity of the plasma membrane localized H+-ATPase, AHA2. While the mechanism of PSY1R-mediated AHA2 phosphorylation has previously been studied in detail, little is known about how PSY1R binds PSY1 peptide ligand and how the intracellular PSY1R kinase domain...

The Perceived Importance of HR duties to Danish line managers

DEFF Research Database (Denmark)

Brandl, Julia; Madsen, Mona Toft; Madsen, Henning

2009-01-01

Today, HR scholars widely acknowledge that realising HRM requires the involvement of all managers and that the personal motivation of line managers plays an important role in their successful involvement. Yet, previous research has neglected to study how line managers rate the importance of parti...

Research on electron beam welding technology of steel HR-4

International Nuclear Information System (INIS)

Guo Peng; Guan Kai

2001-01-01

The electron beam weldability of HR- 4 steels (J75 and J90) is studied and the welding parameters needed for design and usage are presented. The assessment on the effect of mechanical properties by different processing order of welding and heat-treatment is made

HR practices for enhancing sustainable employability : implementation, use, and outcomes

NARCIS (Netherlands)

Ybema, Jan Fekke; van Vuuren, Tinka; van Dam, Karen

2017-01-01

With the aging of the workforce, organizations need to maintain or improve the sustainable employability of their workforce throughout their working life. This raises the question which HR practices increase workers’ sustainable employability at work. The aim of this study is to investigate the

Atypical Employment Relationships and Commitment: Wishful Thinking or HR Challenge?

NARCIS (Netherlands)

Torka, Nicole

2004-01-01

Nowadays, simultaneously maintaining flexible working practices and commitment is an important topic for HR managers since they both can contribute to organisational success. However, many HRM researchers and practitioners are unsure whether these can go together as job security is often seen as a

Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

Energy Technology Data Exchange (ETDEWEB)

Karatas, Hacer; Li, Yangbing; Liu, Liu; Ji, Jiao; Lee, Shirley; Chen, Yong; Yang, Jiuling; Huang, Liyue; Bernard, Denzil; Xu, Jing; Townsend, Elizabeth C.; Cao, Fang; Ran, Xu; Li, Xiaoqin; Wen, Bo; Sun, Duxin; Stuckey, Jeanne A; Lei, Ming; Dou, Yali; Wang, Shaomeng (Michigan)

2017-06-06

We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5–mixed lineage leukemia (MLL) protein–protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis for their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5–MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.

Statistical HR diagrams for one hundred and fifteen thousand proper-motion stars

International Nuclear Information System (INIS)

Luyten, W.J.

1978-01-01

Since regular HR diagrams require apparent magnitudes, colors or spectra, and parallaxes, and such complete data are available for relatively few stars, there may be some advantage in making up diagrams which utilize proper motions instead of parallaxes, and are thus statistically similar to an HR diagram. The reduced proper motion, first used by Hertzsprung, is defined as H=m+5+5log μ, but may also be written as H=M+5log T, where T is the tangential velocity, and is expressed in astronomical units per year. A diagram plotting H against color will thus contain the considerable dispersion in tangential velocity which is a serious disadvantage. However, this is outweighed by two practical advantages. First, the one and the same person who does the proper motion survey can, and does also determine the other two quantities needed. Second, when using data obtained from such a proper motion survey one deals, statistically, with all the stars within a given distance and the results, therefore, are much more representative of the real situation in space than many HR diagrams which often contain an unrealistic preponderance of giants. (Auth.)

Crystallization and preliminary crystallographic analysis of human LR11 Vps10p domain

International Nuclear Information System (INIS)

Nakata, Zenzaburo; Nagae, Masamichi; Yasui, Norihisa; Bujo, Hideaki; Nogi, Terukazu; Takagi, Junichi

2010-01-01

LR11/sorLA contains in its extracellular region a large (∼700-residue) Vps10p domain that is implicated in its intracellular protein-trafficking function. Here, the expression, purification, crystallization and preliminary crystallographic characterization of this domain are described. Low-density lipoprotein receptor (LDLR) relative with 11 binding repeats (LR11; also known as sorLA) is genetically associated with late-onset Alzheimer’s disease and is thought to be involved in neurodegenerative processes. LR11 contains a vacuolar protein-sorting 10 protein (Vps10p) domain. As this domain has been implicated in protein–protein interaction in other receptors, its structure and function are of great biological interest. Human LR11 Vps10p domain was expressed in mammalian cells and the purified protein was crystallized using the hanging-drop vapour-diffusion method. Enzymatic deglycosylation of the sample was critical to obtaining diffraction-quality crystals. Deglycosylated LR11 Vps10p-domain crystals belonged to the hexagonal space group P6 1 22. A diffraction data set was collected to 2.4 Å resolution and a clear molecular-replacement solution was obtained

Human XPC-hHR23B interacts with XPA-RPA in the recognition of triplex-directed psoralen DNA interstrand crosslinks

DEFF Research Database (Denmark)

Thoma, Brian S; Wakasugi, Mitsuo; Christensen, Jesper

2005-01-01

(NER), XPA-RPA, recognizes DNA ICLs. We now report the use of triplex technology to direct a site-specific psoralen ICL to a target DNA substrate to determine whether the human global genome NER damage recognition complex, XPC-hHR23B, recognizes this lesion. Our results demonstrate that XPC-hHR23B...... recognizes psoralen ICLs, which have a structure fundamentally different from other lesions that XPC-hHR23B is known to bind, with high affinity and specificity. XPC-hHR23B and XPA-RPA protein complexes were also observed to bind psoralen ICLs simultaneously, demonstrating not only that psoralen ICLs...... are recognized by XPC-hHR23B alone, but also that XPA-RPA may interact cooperatively with XPC-hHR23B on damaged DNA, forming a multimeric complex. Since XPC-hHR23B and XPA-RPA participate in the recognition and verification of DNA damage, these results support the hypothesis that interplay between components...

Status of SiO2/TiO2 HR coating damage

International Nuclear Information System (INIS)

Lowermilk, W.H.

1979-01-01

The data, observations, and conclusions from a number of experiments on high-reflector (HR) coating damage which were done in FY 1979 are summarized. Damage threshold measurements for the experiments described are presented

The efficiency of SAP in improving the HR performance case study ...

African Journals Online (AJOL)

The efficiency of SAP in improving the HR performance case study: Masdar ... administrative and strategic levels, as well as identifying the contribution of ... Keywords: SAP, human resources management, Masdar Building Materials Company ...

Crystallization and preliminary crystallographic analysis of the fourth FAS1 domain of human BigH3

International Nuclear Information System (INIS)

Yoo, Ji-Ho; Kim, EungKweon; Kim, Jongsun; Cho, Hyun-Soo

2007-01-01

The crystallization and X-ray diffraction analysis of the fourth FAS1 domain of human BigH3 are reported. The protein BigH3 is a cell-adhesion molecule induced by transforming growth factor-β (TGF-β). It consists of four homologous repeat domains known as FAS1 domains; mutations in these domains have been linked to corneal dystrophy. The fourth FAS1 domain was expressed in Escherichia coli B834 (DE3) (a methionine auxotroph) and purified by DEAE anion-exchange and gel-filtration chromatography. The FAS1 domain was crystallized using the vapour-diffusion method. A SAD diffraction data set was collected to a resolution of 2.5 Å at 100 K. The crystal belonged to space group P6 1 or P6 5 and had two molecules per asymmetric unit, with unit-cell parameters a = b = 62.93, c = 143.27 Å, α = β = 90.0, γ = 120.0°

Deep Thermal Infrared Imaging of HR 8799 bcde: New Atmospheric Constraints and Limits on a Fifth Planet

OpenAIRE

Currie, Thayne; Burrows, Adam; Girard, Julien H.; Cloutier, Ryan; Fukagawa, Misato; Sorahana, Satoko; Kuchner, Marc; Kenyon, Scott J.; Madhusudhan, Nikku; Itoh, Yoichi; Jayawardhana, Ray; Matsumura, Soko; Pyo, Tae-Soo

2014-01-01

We present new $L^\\prime$ (3.8 $\\mu m$) and Br-$\\alpha$ (4.05 $\\mu m$) data and reprocessed archival $L^\\prime$ data for the young, planet-hosting star HR 8799 obtained with Keck/NIRC2, VLT/NaCo and Subaru/IRCS. We detect all four HR 8799 planets in each dataset at a moderate to high signal-to-noise (SNR $\\gtrsim$ 6-15). We fail to identify a fifth planet, "HR 8799 f", at $r$ $

Site specific health and safety plan, 100-HR-3 pump and treat. Revision 2

International Nuclear Information System (INIS)

St John, C.H.

1997-09-01

The 100-HR-3 Pump and Treat system is a groundwater remedial action to remove Hexavalent Chromium (Cr+6) from the groundwater underlying the 100-HR-3 Operable Unit. This plan covers operation, maintenance, repairs, resin exchange and equipment removal/installation. The 100-HR-3 Operable Unit addresses groundwater underlying the 100-D Area. The primary groundwater contaminant is Chromium +6. The chromium contamination resulted from the use of sodium dichromate during past reactor operations. Sodium dichromate was used to treat reactor coolant water during reactor operations. The purpose of this Pump and Treat system is to pump contaminated groundwater through above ground ion exchange resin and then return treated water to aquifer. Chromium levels extracted from the wells are anticipated to range in the low parts per billion (∼50 ppb) which is the drinking water limit for Cr+6

E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair.

Science.gov (United States)

Singh, Randeep K; Dagnino, Lina

2016-05-03

Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis.

hrHPV E5 oncoprotein: immune evasion and related immunotherapies.

Science.gov (United States)

de Freitas, Antonio Carlos; de Oliveira, Talita Helena Araújo; Barros, Marconi Rego; Venuti, Aldo

2017-05-25

The immune response is a key factor in the fight against HPV infection and related cancers, and thus, HPV is able to promote immune evasion through the expression of oncogenes. In particular, the E5 oncogene is responsible for modulation of several immune mechanisms, including antigen presentation and inflammatory pathways. Moreover, E5 was suggested as a promising therapeutic target, since there is still no effective medical therapy for the treatment of HPV-related pre-neoplasia and cancer. Indeed, several studies have shown good prospective for E5 immunotherapy, suggesting that it could be applied for the treatment of pre-cancerous lesions. Thus, insofar as the majority of cervical, oropharyngeal and anal cancers are caused by high-risk HPV (hrHPV), mainly by HPV16, the aim of this review is to discuss the immune pathways interfered by E5 oncoprotein of hrHPV highlighting the various aspects of the potential immunotherapeutic approaches.

A combined multiwavelength VLA/ALMA/Chandra study unveils the complex magnetosphere of the B-type star HR5907

Science.gov (United States)

Leto, P.; Trigilio, C.; Oskinova, L. M.; Ignace, R.; Buemi, C. S.; Umana, G.; Ingallinera, A.; Leone, F.; Phillips, N. M.; Agliozzo, C.; Todt, H.; Cerrigone, L.

2018-05-01

We present new radio/millimeter measurements of the hot magnetic star HR 5907 obtained with the VLA and ALMA interferometers. We find that HR 5907 is the most radio luminous early type star in the cm-mm band among those presently known. Its multi-wavelength radio light curves are strongly variable with an amplitude that increases with radio frequency. The radio emission can be explained by the populations of the non-thermal electrons accelerated in the current sheets on the outer border of the magnetosphere of this fast-rotating magnetic star. We classify HR 5907 as another member of the growing class of strongly magnetic fast-rotating hot stars where the gyro-synchrotron emission mechanism efficiently operates in their magnetospheres. The new radio observations of HR 5907 are combined with archival X-ray data to study the physical condition of its magnetosphere. The X-ray spectra of HR 5907 show tentative evidence for the presence of non-thermal spectral component. We suggest that non-thermal X-rays originate a stellar X-ray aurora due to streams of non-thermal electrons impacting on the stellar surface. Taking advantage of the relation between the spectral indices of the X-ray power-law spectrum and the non-thermal electron energy distributions, we perform 3-D modelling of the radio emission for HR 5907. The wavelength-dependent radio light curves probe magnetospheric layers at different heights above the stellar surface. A detailed comparison between simulated and observed radio light curves leads us to conclude that the stellar magnetic field of HR 5907 is likely non-dipolar, providing further indirect evidence of the complex magnetic field topology of HR 5907.

Surface antigens and potential virulence factors from parasites detected by comparative genomics of perfect amino acid repeats

Directory of Open Access Journals (Sweden)

Adler Joël

2007-12-01

Full Text Available Abstract Background Many parasitic organisms, eukaryotes as well as bacteria, possess surface antigens with amino acid repeats. Making up the interface between host and pathogen such repetitive proteins may be virulence factors involved in immune evasion or cytoadherence. They find immunological applications in serodiagnostics and vaccine development. Here we use proteins which contain perfect repeats as a basis for comparative genomics between parasitic and free-living organisms. Results We have developed Reptile http://reptile.unibe.ch, a program for proteome-wide probabilistic description of perfect repeats in proteins. Parasite proteomes exhibited a large variance regarding the proportion of repeat-containing proteins. Interestingly, there was a good correlation between the percentage of highly repetitive proteins and mean protein length in parasite proteomes, but not at all in the proteomes of free-living eukaryotes. Reptile combined with programs for the prediction of transmembrane domains and GPI-anchoring resulted in an effective tool for in silico identification of potential surface antigens and virulence factors from parasites. Conclusion Systemic surveys for perfect amino acid repeats allowed basic comparisons between free-living and parasitic organisms that were directly applicable to predict proteins of serological and parasitological importance. An on-line tool is available at http://genomics.unibe.ch/dora.

The hr locus and the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in newborn mice

Energy Technology Data Exchange (ETDEWEB)

Connor, M J [Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States); Puhvel, S M [Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States); Sakamoto, M [Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States); Nanthur, J [Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States)

1994-12-01

In mice, the recessive mutation hairless (hr) controls the cutaneous response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but its influence on TCDD's systemic toxicity is unclear. To clarify this, we compared the effects of lactational TCDD exposure on standardized litters of newborn HRS/J mice homozygous for either hr or + that were fostered by haired dams exposed to 0, 6, 8 or 12 [mu]g TCDD/kg body weight on postnatal day 0. At 12 [mu]g/kg, TCDD was lethal to both haired and hairless pups. At the lower doses (6 and 8 [mu]g/kg) the survival of hr/hr pups was significantly lower than +/+ pups. Affected pups succumbed following a 1 to 2-day period of cachexia and wasting. As has been reported for other mouse strains, TCDD exposure impacted on their neonatal development and lessened the time to eye opening for both haired and hairless pups. However, the hairless animals were affected at lower doses than were the haired. The results of this study document that the hr/hr genotype does influence the systemic toxicity of TCDD in mice. (orig.)

The hr locus and the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in newborn mice

Energy Technology Data Exchange (ETDEWEB)

Connor, M.J. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States)); Puhvel, S.M. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States)); Sakamoto, M. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States)); Nanthur, J. (Div. of Dermatology, Dept. of Medicine, UCLA School of Medicine, Los Angeles, CA (United States) Research Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, CA (United States))

1994-12-01

In mice, the recessive mutation hairless (hr) controls the cutaneous response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but its influence on TCDD's systemic toxicity is unclear. To clarify this, we compared the effects of lactational TCDD exposure on standardized litters of newborn HRS/J mice homozygous for either hr or + that were fostered by haired dams exposed to 0, 6, 8 or 12 [mu]g TCDD/kg body weight on postnatal day 0. At 12 [mu]g/kg, TCDD was lethal to both haired and hairless pups. At the lower doses (6 and 8 [mu]g/kg) the survival of hr/hr pups was significantly lower than +/+ pups. Affected pups succumbed following a 1 to 2-day period of cachexia and wasting. As has been reported for other mouse strains, TCDD exposure impacted on their neonatal development and lessened the time to eye opening for both haired and hairless pups. However, the hairless animals were affected at lower doses than were the haired. The results of this study document that the hr/hr genotype does influence the systemic toxicity of TCDD in mice. (orig.)

Spectral-domain Optical Coherence Tomography Retinal and Choroidal Thickness Metric Repeatability in Age-related Macular Degeneration

DEFF Research Database (Denmark)

Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie

2016-01-01

: Enrolled patients underwent repeated SDOCT imaging using the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). A single technician certified for clinical trials took 3 macular volume scans. Retinal thicknesses were calculated for each of the 9 Early Treatment Diabetic Retinopathy Study (ETDRS...... was 34.7 μm (95% CI 33.7-35.7 μm). CONCLUSIONS: This study suggests that a change of greater than 31 μm in Spectralis SDOCT-derived retinal thickness measurement of the central macular subfield and 35 μm in subfoveal choroidal thickness is necessary to detect true clinical change associated with disease...

A critical role of the nuclear receptor HR3 in regulation of gonadotrophic cycles of the mosquito Aedes aegypti.

Directory of Open Access Journals (Sweden)

Daniel Mane-Padros

Full Text Available The orphan nuclear receptor HR3 is essential for developmental switches during insect development and metamorphosis regulated by 20-hydroxyecdysone (20E. Reproduction of female mosquitoes of the major vector of Dengue fever, Aedes aegypti, is cyclic because of its dependence on blood feeding. 20E is an important hormone regulating vitellogenic events in this mosquito; however, any role for HR3 in 20E-driven reproductive events has not been known. Using RNA interference (RNAi approach, we demonstrated that Aedes HR3 plays a critical role in a timely termination of expression of the vitellogenin (Vg gene encoding the major yolk protein precursor. It is also important for downregulation of the Target-of-Rapamycin pathway and activation of programmed autophagy in the Aedes fat body at the end of vitellogenesis. HR3 is critical in activating betaFTZ-F1, EcRB and USPA, the expressions of which are highly elevated at the end of vitellogenesis. RNAi depletion of HR3 (iHR3 prior to the first gonadotrophic cycle affects a normal progression of the second gonadotrophic cycle. Most of ovaries 24 h post second blood meal from iHR3 females in the second cycle were small with follicles that were only slightly different in length from of those of resting stage. In addition, these iHR3 females laid a significantly reduced number of eggs per mosquito as compared to those of iMal and the wild type. Our results indicate an important role of HR3 in regulation of 20E-regulated developmental switches during reproductive cycles of A. aegypti females.

Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

Science.gov (United States)

Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

2014-02-01

The Gd5Ge2Si2 alloy and the off-stoichiometric Ni50Mn35In15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd5Ge2Si2 and Ni50Mn35In15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

International Nuclear Information System (INIS)

Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

2014-01-01

The Gd 5 Ge 2 Si 2 alloy and the off-stoichiometric Ni 50 Mn 35 In 15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd 5 Ge 2 Si 2 and Ni 50 Mn 35 In 15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis

Binding of HIV-1 gp41-directed neutralizing and non-neutralizing fragment antibody binding domain (Fab and single chain variable fragment (ScFv antibodies to the ectodomain of gp41 in the pre-hairpin and six-helix bundle conformations.

Directory of Open Access Journals (Sweden)

John M Louis

Full Text Available We previously reported a series of antibodies, in fragment antigen binding domain (Fab formats, selected from a human non-immune phage library, directed against the internal trimeric coiled-coil of the N-heptad repeat (N-HR of HIV-1 gp41. Broadly neutralizing antibodies from that series bind to both the fully exposed N-HR trimer, representing the pre-hairpin intermediate state of gp41, and to partially-exposed N-HR helices within the context of the gp41 six-helix bundle. While the affinities of the Fabs for pre-hairpin intermediate mimetics vary by only 2 to 20-fold between neutralizing and non-neutralizing antibodies, differences in inhibition of viral entry exceed three orders of magnitude. Here we compare the binding of neutralizing (8066 and non-neutralizing (8062 antibodies, differing in only four positions within the CDR-H2 binding loop, in Fab and single chain variable fragment (ScFv formats, to several pre-hairpin intermediate and six-helix bundle constructs of gp41. Residues 56 and 58 of the mini-antibodies are shown to be crucial for neutralization activity. There is a large differential (≥ 150-fold in binding affinity between neutralizing and non-neutralizing antibodies to the six-helix bundle of gp41 and binding to the six-helix bundle does not involve displacement of the outer C-terminal helices of the bundle. The binding stoichiometry is one six-helix bundle to one Fab or three ScFvs. We postulate that neutralization by the 8066 antibody is achieved by binding to a continuum of states along the fusion pathway from the pre-hairpin intermediate all the way to the formation of the six-helix bundle, but prior to irreversible fusion between viral and cellular membranes.

Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41.

Science.gov (United States)

Sabin, Charles; Corti, Davide; Buzon, Victor; Seaman, Mike S; Lutje Hulsik, David; Hinz, Andreas; Vanzetta, Fabrizia; Agatic, Gloria; Silacci, Chiara; Mainetti, Lara; Scarlatti, Gabriella; Sallusto, Federica; Weiss, Robin; Lanzavecchia, Antonio; Weissenhorn, Winfried

2010-11-18

The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool.

The high resolution optical instruments for the Pleiades HR Earth observation satellites

Science.gov (United States)

Gaudin-Delrieu, Catherine; Lamard, Jean-Luc; Cheroutre, Philippe; Bailly, Bruno; Dhuicq, Pierre; Puig, Olivier

2017-11-01

Coming after the SPOT satellites series, PLEIADESHR is a CNES optical high resolution satellite dedicated to Earth observation, part of a larger optical and radar multi-sensors system, ORFEO, which is developed in cooperation between France and Italy for dual Civilian and Defense use. The development of the two PLEIADES-HR cameras was entrusted by CNES to Thales Alenia Space. This new generation of instrument represents a breakthrough in comparison with the previous SPOT instruments owing to a significant step in on-ground resolution, which approaches the capabilities of aerial photography. The PLEIADES-HR instrument program benefits from Thales Alenia Space long and successful heritage in Earth observation from space. The proposed solution benefits from an extensive use of existing products, Cannes Space Optics Centre facilities, unique in Europe, dedicated to High Resolution instruments. The optical camera provides wide field panchromatic images supplemented by 4 multispectral channels with narrow spectral bands. The optical concept is based on a four mirrors Korsch telescope. Crucial improvements in detector technology, optical fabrication and electronics make it possible for the PLEIADES-HR instrument to achieve the image quality requirements while respecting the drastic limitations of mass and volume imposed by the satellite agility needs and small launchers compatibility. The two flight telescopes were integrated, aligned and tested. After the integration phase, the alignment, mainly based on interferometric measurements in vacuum chamber, was successfully achieved within high accuracy requirements. The wave front measurements show outstanding performances, confirmed, after the integration of the PFM Detection Unit, by MTF measurements on the Proto-Flight Model Instrument. Delivery of the proto flight model occurred mi-2008. The FM2 Instrument delivery is planned Q2-2009. The first optical satellite launch of the PLEIADES-HR constellation is foreseen

Monitoring training status with HR measures: do all roads lead to Rome?

Directory of Open Access Journals (Sweden)

Martin eBuchheit

2014-02-01

Full Text Available Monitoring an athlete's physiological status in response to various types and volumes of (aerobic-oriented training can provide useful information for optimizing training programs. Measures of resting, exercise and recovery heart rate (HR are receiving increasing interest for monitoring fatigue, fitness and endurance performance responses, which has direct implications for adjusting training load 1 daily during specific training blocks and 2 throughout the competitive season. These measures are still not widely implemented to monitor athletes’ responses to training load, probably because of apparent contradictory findings in the literature. In this review I contend that most of the contradictory findings are related to methodological inconsistencies and/or misinterpretation of the data rather than to limitations of heart rate measures to accurately inform on training status. I also provide evidence that measures derived from 5-min (almost daily recordings of resting (indices capturing beat-to-beat changes in HR, reflecting parasympathetic activity and submaximal exercise (30- to 60-s average HR are likely the most useful monitoring tools. For appropriate interpretation at the individual level, changes in a given measure should be interpreted by taking into account the error of measurement and the smallest important change of the measure, as well as the training context (training phase, load and intensity distribution. The decision to use a given measure should be based upon the level of information that is required by the athlete, the marker’s sensitivity to changes in training status and the practical constrains required for the measurements. However, measures of HR cannot inform on all aspects of wellness, fatigue and performance, so their use in combination with daily training logs, psychometric questionnaires and non-invasive, cost-effective performance tests such as a countermovement jump may offer a complete solution to monitor

All-photonic quantum repeaters

Science.gov (United States)

Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

2015-01-01

Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

Site specific health and safety plan, 100-HR-3 pump and treat. Revision 1

International Nuclear Information System (INIS)

Tuttle, B.G.

1996-06-01

The 100-HR-3 Operable Unit encompasses groundwater contamination underlying the 100-D and 100-H Areas. The primary contaminate is chromium VI. The sources of chromium contamination resulted from the use of sodium dichromate during past reactor operations. The purpose of the 100-HR-3 Pump-and-Treat system is to pump contaminated groundwater through aboveground ion exchange resin and then return the treated waster to the aquifer. This plan covers operation, maintenance, repairs, and pump removal/installation

Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures

Directory of Open Access Journals (Sweden)

Hayes Michael L

2012-05-01

Full Text Available Abstract Background Pentatricopeptide repeat (PPR proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82 and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. Results All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3’ UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. Conclusion PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative

Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures.

Science.gov (United States)

Hayes, Michael L; Giang, Karolyn; Mulligan, R Michael

2012-05-14

Pentatricopeptide repeat (PPR) proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82) and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3' UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative selection even in the absence of an editing site target

Design of the high resolution optical instrument for the Pleiades HR Earth observation satellites

Science.gov (United States)

Lamard, Jean-Luc; Gaudin-Delrieu, Catherine; Valentini, David; Renard, Christophe; Tournier, Thierry; Laherrere, Jean-Marc

2017-11-01

As part of its contribution to Earth observation from space, ALCATEL SPACE designed, built and tested the High Resolution cameras for the European intelligence satellites HELIOS I and II. Through these programmes, ALCATEL SPACE enjoys an international reputation. Its capability and experience in High Resolution instrumentation is recognised by the most customers. Coming after the SPOT program, it was decided to go ahead with the PLEIADES HR program. PLEIADES HR is the optical high resolution component of a larger optical and radar multi-sensors system : ORFEO, which is developed in cooperation between France and Italy for dual Civilian and Defense use. ALCATEL SPACE has been entrusted by CNES with the development of the high resolution camera of the Earth observation satellites PLEIADES HR. The first optical satellite of the PLEIADES HR constellation will be launched in mid-2008, the second will follow in 2009. To minimize the development costs, a mini satellite approach has been selected, leading to a compact concept for the camera design. The paper describes the design and performance budgets of this novel high resolution and large field of view optical instrument with emphasis on the technological features. This new generation of camera represents a breakthrough in comparison with the previous SPOT cameras owing to a significant step in on-ground resolution, which approaches the capabilities of aerial photography. Recent advances in detector technology, optical fabrication and electronics make it possible for the PLEIADES HR camera to achieve their image quality performance goals while staying within weight and size restrictions normally considered suitable only for much lower performance systems. This camera design delivers superior performance using an innovative low power, low mass, scalable architecture, which provides a versatile approach for a variety of imaging requirements and allows for a wide number of possibilities of accommodation with a mini

Transgenic Cotton Plants Expressing the HaHR3 Gene Conferred Enhanced Resistance to Helicoverpa armigera and Improved Cotton Yield.

Science.gov (United States)

Han, Qiang; Wang, Zhenzhen; He, Yunxin; Xiong, Yehui; Lv, Shun; Li, Shupeng; Zhang, Zhigang; Qiu, Dewen; Zeng, Hongmei

2017-08-30

RNA interference (RNAi) has been developed as an efficient technology. RNAi insect-resistant transgenic plants expressing double-stranded RNA (dsRNA) that is ingested into insects to silence target genes can affect the viability of these pests or even lead to their death. HaHR3 , a molt-regulating transcription factor gene, was previously selected as a target expressed in bacteria and tobacco plants to control Helicoverpa armigera by RNAi technology. In this work, we selected the dsRNA- HaHR3 fragment to silence HaHR3 in cotton bollworm for plant mediated-RNAi research. A total of 19 transgenic cotton lines expressing HaHR3 were successfully cultivated, and seven generated lines were used to perform feeding bioassays. Transgenic cotton plants expressing ds HaHR3 were shown to induce high larval mortality and deformities of pupation and adult eclosion when used to feed the newly hatched larvae, and 3rd and 5th instar larvae of H. armigera . Moreover, HaHR3 transgenic cotton also demonstrated an improved cotton yield when compared with controls.

HR diagrams derived from the Michigan Spectral Catalogue

International Nuclear Information System (INIS)

Houk, N.; Fesen, R.

1978-01-01

The authors present some HR diagrams constructed using data from the Michigan Spectral Catalogues. Houk (1975) has been systematically reclassifying the Henry Draper stars on the MK system, from the south pole northward. Objective-prism plates, with a reciprocal dispersion of 108 A/mm, have been taken with the Michigan Curtis Schmidt telescope at Cerro Tololo Inter-American Observatory in Chile. The spectra are classified visually from the plates, and the results are put onto IBM cards and magnetic tape from which the catalogues are produced. (Auth.)

Calcium isotope measurement by combined HR-MC-ICPMS and TIMS

DEFF Research Database (Denmark)

Schiller, Martin; Paton, Chad; Bizzarro, Martin

2012-01-01

studies demonstrate that it is possible to measure the mass-dependent Ca isotope composition of terrestrial materials using HR-MC-ICPMS with an external reproducibility comparable to that typically obtained with double spike TIMS techniques. The resolution of the mass-independent 43Ca, 46Ca and 48Ca data...

HR Manager Leadership in Quality Improvement in a College Environment

Science.gov (United States)

Sharabi, Moshe

2010-01-01

Purpose: The purpose of this paper is to present the influence of the human resource (HR) manager on the quality of service in an academic college, and the human resource management (HRM) outcomes of the process. Design/methodology/approach: The paper relates to a customer satisfaction survey. More than 120 questionnaires were completed by the…

Prospective observational study on assessing the hemodynamic relevance of patent ductus arteriosus with frequency domain near-infrared spectroscopy.

Science.gov (United States)

Schwarz, Christoph E; Preusche, Antonio; Wolf, Martin; Poets, Christian F; Franz, Axel R

2018-02-16

What constitutes a hemodynamically relevant patent ductus arteriosus (hrPDA) in preterm infants is unclear. Different clinical and echocardiographic parameters are used, but a gold standard definition is lacking. Our objective was to evaluate associations between regional cerebral tissue oxygen saturation (rcStO 2 ), fraction of tissue oxygen extraction (rcFtO 2 E) measured by frequency domain near-infrared spectroscopy (fd-NIRS) and their correlation to echocardiographic, Doppler-ultrasound, and clinical parameters in preterm infants with and without a hrPDA. In this prospective observational study, 22 infants standard deviation (normalised to a median Hb of 13.8 mg/dl) was 57 ±5% for rcStO 2 and 0.39 ±0.05 for rcFtO 2 E. Comparing no-hrPDA with hrPDA infants, there were no significant differences in mean rcStO 2 (58 ±5% vs. 54 ±5%; p = .102), but in mean rcFtO 2 E (0.38 ±0.05 vs. 0.43 ±0.05; p = .038). Echocardiographic parameter and Doppler indices did not correlate with cerebral oxygenation. Oxygen transport capacity of the blood may confound NIRS data interpretation. Cerebral oxygenation determined by fd-NIRS provided additional information for PDA treatment decisions not offered by routine investigations. Whether indicating PDA therapy based on echocardiography complemented by data on cerebral oxygenation results in better outcomes should be investigated in future studies.

Sex and family history of cardiovascular disease influence heart rate variability during stress among healthy adults.

Science.gov (United States)

Emery, Charles F; Stoney, Catherine M; Thayer, Julian F; Williams, DeWayne; Bodine, Andrew

2018-07-01

Studies of sex differences in heart rate variability (HRV) typically have not accounted for the influence of family history (FH) of cardiovascular disease (CVD). This study evaluated sex differences in HRV response to speech stress among men and women (age range 30-49 years) with and without a documented FH of CVD. Participants were 77 adults (mean age = 39.8 ± 6.2 years; range: 30-49 years; 52% female) with positive FH (FH+, n = 32) and negative FH (FH-, n = 45) of CVD, verified with relatives of participants. Cardiac activity for all participants was recorded via electrocardiogram during a standardized speech stress task with three phases: 5-minute rest, 5-minute speech, and 5-minute recovery. Outcomes included time domain and frequency domain indicators of HRV and heart rate (HR) at rest and during stress. Data were analyzed with repeated measures analysis of variance, with sex and FH as between subject variables and time/phase as a within subject variable. Women exhibited higher HR than did men and greater HR reactivity in response to the speech stress. However, women also exhibited greater HRV in both the time and frequency domains. FH+ women generally exhibited elevated HRV, despite the elevated risk of CVD associated with FH+. Although women participants exhibited higher HR at rest and during stress, women (both FH+ and FH-) also exhibited elevated HRV reactivity, reflecting greater autonomic control. Thus, enhanced autonomic function observed in prior studies of HRV among women is also evident among FH+ women during a standardized stress task. Copyright © 2018 Elsevier Inc. All rights reserved.

Characterization of a Fasciola gigantica protein carrying two DM9 domains reveals cellular relocalization property.

Science.gov (United States)

Phadungsil, Wansika; Smooker, Peter M; Vichasri-Grams, Suksiri; Grams, Rudi

2016-01-01

Even at the present age of whole-organism analysis, e.g., genomics, transcriptomics, and proteomics, the biological roles of many proteins remain unresolved. Classified among the proteins of unknown function is a family of proteins harboring repeats of the DM9 domain, a 60-75 amino acids motif first described in a small number of Drosophila melanogaster proteins. Proteins may carry two or more DM9 domains either in combination with other domains or as their sole constituent. Here we have characterized a 16.8 kDa Fasciola gigantica protein comprising two tandem repeated DM9 domains (FgDM9-1). The protein was located in the parenchyma of the immature and mature parasite and consequently it was not detected in the ES product of the parasite but only in the whole worm extract. Interestingly, extraction with SDS yielded a substantially higher amount of the protein suggesting association with insoluble cell components. In Sf9 insect cells a heterologously expressed EGFP-FgDM9-1 chimera showed cell-wide distribution but relocated to vesicle-like structures in the cytoplasm after stimulating cellular stress by bacteria, heat shock or chloroquine. These structures did not colocalize with the markers of endocytosis/phagocytosis ubiquitin, RAB7, GABARAP. The same behavior was noted for Aedes aegypti PRS1, a homologous mosquito DM9 protein as a positive control while EGFP did not exhibit such relocation in the insect cells. Cross-linking experiments on soluble recombinant FgDM9-1 indicated that the protein can undergo specific oligomerization. It is speculated that proteins carrying the DM9 domain have a role in vesicular transport in flatworms and insects. Copyright © 2016 Elsevier B.V. All rights reserved.

Microturbulence as a third dimension in the G-K giant region of the HR diagram

International Nuclear Information System (INIS)

Foy, R.

1978-01-01

The structure of the HR diagram in the G-K giant region is complex, because of the funneling effect and of the intersection of evolutionary tracks for different stellar masses. Therefore it is impossible to derive the age of a cool giant from its location in the HR diagram alone. To remove this indeterminacy a third dimension is needed, and the author suggests microturbulence as the appropriate observational parameter. (Auth.)

Doctor-patient relationships (DPR) in China: managers and clinicians’ twofold pathways from commitment HR practices

OpenAIRE

Ma, S.; Xu, X.; Trigo, V.; Ramalho, N. J. C.

2017-01-01

Purpose: The first objective of this research is to develop and test theory on how commitment human resource (HR) practices affect hospital professionals’ job satisfaction that motivates them to generate desirable patient care and subsequently improve doctor-patient relationships (DPR). The second objective is to examine how commitment HR practices influence in different ways hospital managers and clinicians. Methodology: Using a cross-sectional survey, data were collect from 508 clinicians a...

Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin

Science.gov (United States)

Bhutoria, Savita

2016-01-01

Abstract The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein‐protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV‐1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c‐MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1. PMID:27261671

Next HR Department public meeting

CERN Multimedia

2016-01-01

Dear Colleagues, I am pleased to invite you to the next public meeting organized by the HR Department, which will take place on Tuesday 28 June at 3 p.m. in the Council Chamber. A drink will be served after the meeting as of 16:30 This meeting will be the opportunity to revisit the specificities of the Career Structure measures and Benchmark Jobs, what they entail and how they will be implemented, and to answer your questions. This meeting is also important for me on a personal note, as I will bid you farewell, at least for a few years, taking special leave as of 1 August 2016 to take up the position of Director-General for Human Resources at the European Central Bank in Frankfurt.  Should you not be able to attend the meeting, it can also be followed via Webcast and the recording will be made available on Indico. I look forward to meeting you. Best regards, Anne-Sylvie Catherin Head of the Human Resources Department

A Method against Interrupted-Sampling Repeater Jamming Based on Energy Function Detection and Band-Pass Filtering

Directory of Open Access Journals (Sweden)

Hui Yuan

2017-01-01

Full Text Available Interrupted-sampling repeater jamming (ISRJ is a new kind of coherent jamming to the large time-bandwidth linear frequency modulation (LFM signal. Many jamming modes, such as lifelike multiple false targets and dense false targets, can be made through setting up different parameters. According to the “storage-repeater-storage-repeater” characteristics of the ISRJ and the differences in the time-frequency-energy domain between the ISRJ signal and the target echo signal, one new method based on the energy function detection and band-pass filtering is proposed to suppress the ISRJ. The methods mainly consist of two parts: extracting the signal segments without ISRJ and constructing band-pass filtering function with low sidelobe. The simulation results show that the method is effective in the ISRJ with different parameters.

Reduction of starch granule size by expression of an engineered tandem starch-binding domain in potato plants

NARCIS (Netherlands)

Ji, Q.; Oomen, R.J.F.J.; Vincken, J.P.; Bolam, D.N.; Gilbert, H.J.; Suurs, L.C.J.M.; Visser, R.G.F.

2004-01-01

Granule size is an important parameter when using starch in industrial applications. An artificial tandem repeat of a family 20 starch-binding domain (SBD2) was engineered by two copies of the SBD derived from Bacillus circulans cyclodextrin glycosyltransferase via the Pro-Thr-rich linker peptice

78 FR 65594 - Vehicular Repeaters

Science.gov (United States)

2013-11-01

... coordinators estimate the effect on coordination fees? Does the supposed benefit that mobile repeater stations... allow the licensing and operation of vehicular repeater systems and other mobile repeaters by public... email: [email protected] or phone: 202-418- 0530 or TTY: 202-418-0432. For detailed instructions for...

CARF and WYL domains: ligand-binding regulators of prokaryotic defense systems

Directory of Open Access Journals (Sweden)

Kira eMakarova

2014-04-01

Full Text Available CRISPR-Cas adaptive immunity systems of bacteria and archaea insert fragments of virus or plasmid DNA as spacer sequences into CRISPR repeat loci. Processed transcripts encompassing these spacers guide the cleavage of the cognate foreign DNA or RNA. Most CRISPR-Cas loci, in addition to recognized cas genes, also include genes that are not directly implicated in spacer acquisition, CRISPR transcript processing or interference. Here we comprehensively analyze sequences, structures and genomic neighborhoods of one of the most widespread groups of such genes that encode proteins containing a predicted nucleotide-binding domain with a Rossmann-like fold, which we denote CARF (CRISPR-associated Rossmann fold. Several CARF protein structures have been determined but functional characterization of these proteins is lacking. The CARF domain is most frequently combined with a C-terminal winged helix-turn-helix DNA-binding domain and effector domains most of which are predicted to possess DNase or RNase activity. Divergent CARF domains are also found in RtcR proteins, sigma-54 dependent regulators of the rtc RNA repair operon. CARF genes frequently co-occur with those coding for proteins containing the WYL domain with the Sm-like SH3 β-barrel fold, which is also predicted to bind ligands. CRISPR-Cas and possibly other defense systems are predicted to be transcriptionally regulated by multiple ligand-binding proteins containing WYL and CARF domains which sense modified nucleotides and nucleotide derivatives generated during virus infection. We hypothesize that CARF domains also transmit the signal from the bound ligand to the fused effector domains which attack either alien or self nucleic acids, resulting, respectively, in immunity complementing the CRISPR-Cas action or in dormancy/programmed cell death.

Tevatron serial data repeater system

International Nuclear Information System (INIS)

Ducar, R.J.

1981-01-01

A ten megabit per second serial data repeater system has been developed for the 6.28km Tevatron accelerator. The repeaters are positioned at each of the thirty service buildings and accommodate control and abort system communications as well as distribution of the Tevatron time and energy clocks. The repeaters are transparent to the particular protocol of the transmissions. Serial data are encoded locally as unipolar two volt signals employing the self-clocking Manchester Bi-Phase code. The repeaters modulate the local signals to low-power bursts of 50 MHz rf carrier for the 260m transmission between service buildings. The repeaters also demodulate the transmission and restructure the data for local utilization. The employment of frequency discrimination techniques yields high immunity to the characteristic noise spectrum

Atmospheric retrieval analysis of the directly imaged exoplanet HR 8799b

Energy Technology Data Exchange (ETDEWEB)

Lee, Jae-Min [University of Zürich, Institute for Theoretical Physics, Winterthurerstrasse 190, CH-8057 Zürich (Switzerland); Heng, Kevin [University of Bern, Center for Space and Habitability, Sidlerstrasse 5, CH-3012 Bern (Switzerland); Irwin, Patrick G. J., E-mail: lee@physik.uzh.ch, E-mail: kevin.heng@csh.unibe.ch, E-mail: irwin@atm.ox.ac.uk [University of Oxford, Atmospheric, Oceanic and Planetary Physics, Clarendon Laboratory, Parks Road, Oxford OX1 3PU (United Kingdom)

2013-12-01

Directly imaged exoplanets are unexplored laboratories for the application of the spectral and temperature retrieval method, where the chemistry and composition of their atmospheres are inferred from inverse modeling of the available data. As a pilot study, we focus on the extrasolar gas giant HR 8799b, for which more than 50 data points are available. We upgrade our non-linear optimal estimation retrieval method to include a phenomenological model of clouds that requires the cloud optical depth and monodisperse particle size to be specified. Previous studies have focused on forward models with assumed values of the exoplanetary properties; there is no consensus on the best-fit values of the radius, mass, surface gravity, and effective temperature of HR 8799b. We show that cloud-free models produce reasonable fits to the data if the atmosphere is of super-solar metallicity and non-solar elemental abundances. Intermediate cloudy models with moderate values of the cloud optical depth and micron-sized particles provide an equally reasonable fit to the data and require a lower mean molecular weight. We report our best-fit values for the radius, mass, surface gravity, and effective temperature of HR 8799b. The mean molecular weight is about 3.8, while the carbon-to-oxygen ratio is about unity due to the prevalence of carbon monoxide. Our study emphasizes the need for robust claims about the nature of an exoplanetary atmosphere to be based on analyses involving both photometry and spectroscopy and inferred from beyond a few photometric data points, such as are typically reported for hot Jupiters.

Limited field investigation report for the 100-HR-2 Operable Unit

International Nuclear Information System (INIS)

1995-07-01

This report summarizes the data collection and analysis activities conducted during the 100-HR-2 Operable Unit investigative phase and the associated qualitative risk assessment. The 100-HR-2 Operable Unit contains solid waste burial grounds, an ash pit, burn pits, electrical facilities, septic systems, and support facilities. All known and suspected areas of contamination were classified as solid waste burial grounds or low-priority waste sites based on the collective knowledge of the operable unit managers (representatives from the US Department of Energy, the US Environmental Protection Agency, and Washington State Department of Ecology during the preparation of the 100-HR-2 Operable Unit Work Plan (DOE-RL 1993f). Solid waste burial grounds were judged to pose sufficient risk(s), through one or more pathways, to require evaluation for an interim remedial measure as per the Hanford Past-Practice Strategy (DOE-RL 1991) and negotiations with the Department of Energy, US Environmental Protection Agency, and Washington State Department of Ecology. An interim remedial measure is intended to achieve remedies that are likely to lead to a final record of decision. Low-priority sites are those judged not to pose significant risk to require the streamlined evaluation. There were six low-priority waste sites and seven solid waste burial grounds identified. The purpose of this report is to: (1) provide a summary of site investigative activities; (2) refine the conceptual exposure model (as needed); (3) identify chemical- and location-specific corrective action requirements; and 4) provide a human health and ecological QRA associated with solid waste burial grounds

Beyond cross-domain learning: Multiple-domain nonnegative matrix factorization

KAUST Repository

Wang, Jim Jing-Yan; Gao, Xin

2014-01-01

Traditional cross-domain learning methods transfer learning from a source domain to a target domain. In this paper, we propose the multiple-domain learning problem for several equally treated domains. The multiple-domain learning problem assumes that samples from different domains have different distributions, but share the same feature and class label spaces. Each domain could be a target domain, while also be a source domain for other domains. A novel multiple-domain representation method is proposed for the multiple-domain learning problem. This method is based on nonnegative matrix factorization (NMF), and tries to learn a basis matrix and coding vectors for samples, so that the domain distribution mismatch among different domains will be reduced under an extended variation of the maximum mean discrepancy (MMD) criterion. The novel algorithm - multiple-domain NMF (MDNMF) - was evaluated on two challenging multiple-domain learning problems - multiple user spam email detection and multiple-domain glioma diagnosis. The effectiveness of the proposed algorithm is experimentally verified. © 2013 Elsevier Ltd. All rights reserved.

Beyond cross-domain learning: Multiple-domain nonnegative matrix factorization

KAUST Repository

Wang, Jim Jing-Yan

2014-02-01

Traditional cross-domain learning methods transfer learning from a source domain to a target domain. In this paper, we propose the multiple-domain learning problem for several equally treated domains. The multiple-domain learning problem assumes that samples from different domains have different distributions, but share the same feature and class label spaces. Each domain could be a target domain, while also be a source domain for other domains. A novel multiple-domain representation method is proposed for the multiple-domain learning problem. This method is based on nonnegative matrix factorization (NMF), and tries to learn a basis matrix and coding vectors for samples, so that the domain distribution mismatch among different domains will be reduced under an extended variation of the maximum mean discrepancy (MMD) criterion. The novel algorithm - multiple-domain NMF (MDNMF) - was evaluated on two challenging multiple-domain learning problems - multiple user spam email detection and multiple-domain glioma diagnosis. The effectiveness of the proposed algorithm is experimentally verified. © 2013 Elsevier Ltd. All rights reserved.

The crystal structures of EAP domains from Staphylococcus aureus reveal an unexpected homology to bacterial superantigens.

Science.gov (United States)

Geisbrecht, Brian V; Hamaoka, Brent Y; Perman, Benjamin; Zemla, Adam; Leahy, Daniel J

2005-04-29

The Eap (extracellular adherence protein) of Staphylococcus aureus functions as a secreted virulence factor by mediating interactions between the bacterial cell surface and several extracellular host proteins. Eap proteins from different Staphylococcal strains consist of four to six tandem repeats of a structurally uncharacterized domain (EAP domain). We have determined the three-dimensional structures of three different EAP domains to 1.8, 2.2, and 1.35 A resolution, respectively. These structures reveal a core fold that is comprised of an alpha-helix lying diagonally across a five-stranded, mixed beta-sheet. Comparison of EAP domains with known structures reveals an unexpected homology with the C-terminal domain of bacterial superantigens. Examination of the structure of the superantigen SEC2 bound to the beta-chain of a T-cell receptor suggests a possible ligand-binding site within the EAP domain (Fields, B. A., Malchiodi, E. L., Li, H., Ysern, X., Stauffacher, C. V., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. (1996) Nature 384, 188-192). These results provide the first structural characterization of EAP domains, relate EAP domains to a large class of bacterial toxins, and will guide the design of future experiments to analyze EAP domain structure/function relationships.

Global well-posedness for Schrödinger equation with derivative in H(R)

Science.gov (United States)

Miao, Changxing; Wu, Yifei; Xu, Guixiang

In this paper, we consider the Cauchy problem of the cubic nonlinear Schrödinger equation with derivative in H(R). This equation was known to be the local well-posedness for s⩾1/2 > (Takaoka, 1999 [27]), ill-posedness for s (Biagioni and Linares, 2001 [1], etc.) and global well-posedness for s>1/2 > (I-team, 2002 [10]). In this paper, we show that it is global well-posedness in the endpoint space H(R), which remained open previously. The main approach is the third generation I-method combined with a new resonant decomposition technique. The resonant decomposition is applied to control the singularity coming from the resonant interaction.

Acute hyperhydration reduces athlete biological passport OFF-hr score

DEFF Research Database (Denmark)

Bejder Rasmussen, Jacob; Hoffmann, M F; Ashenden, M

2016-01-01

Anecdotal evidence suggests that athletes hyperhydrate to mask prohibited substances in urine and potentially counteract suspicious fluctuations in blood parameters in the athlete biological passport (ABP). It is examined if acute hyperhydration changes parameters included in the ABP. Twenty...... ingestion, and 54% (n = 19), 45%, and 47% (n = 19) were identified 40, 60, and 80 min, respectively, after ingestion. In conclusion, acute hyperhydration reduces ABP OFF-hr and reduces ABP sensitivity....

High-performance HR practices, positive affect and employee outcomes

OpenAIRE

Mostafa, Ahmed

2017-01-01

Purpose – The purpose of this paper is to provide insight into the affective or emotional mechanisms that underlie the relationship between high-performance HR practices (HPHRP) and employee attitudes and behaviours. Drawing on affective events theory (AET), this paper examines a mediation model in which HPHRP influence positive affect which in turn affects job satisfaction and organizational citizenship behaviours (OCBs). Design/methodology/approach – Two-wave data was collected from a sampl...

Repeat Customer Success in Extension

Science.gov (United States)

Bess, Melissa M.; Traub, Sarah M.

2013-01-01

Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

Film repeats in radiology department

International Nuclear Information System (INIS)

Suwan, A. Z.; Al-Shakharah, A. I

1997-01-01

During a one year period, 4910 radiographs of 55780 films were repeated. The objective of our study was to analyse and to classify the causes in order to minimize the repeats, cut the expenses and to provide optimal radiographs for accurate diagnosis. Analysis of the different factors revealed that, 43.6% of film repeats in our service were due to faults in exposure factors, centering comprises 15.9% of the repeats, while too much collimation was responsible for 7.6% of these repeats. All of which can be decreased by awareness and programmed training of technicians. Film blurring caused by patient motion was also responsible for 4.9% for radiographs reexamination, which can be minimized by detailed explanation to the patient and providing the necessary privacy. Fogging of X-Ray films by improper storage or inadequate handling or processing faults were responsible for 14.5% in repeats in our study. Methods and criteria for proper storage and handling of films were discussed. Recommendation for using modern day-light and laser processor has been high lighted. Artefacts are noticeably high in our cases, due to spinal dresses and frequent usage of precious metals for c osmotic purposes in this part of the world. The repeated films comprise 8.8% of all films We conclude that, the main factor responsible for repeats of up to 81.6% of cases was the technologists, thus emphasizing the importance of adequate training of the technologists. (authors). 15 refs., 9 figs., 1 table

Repeat migration and disappointment.

Science.gov (United States)

Grant, E K; Vanderkamp, J

1986-01-01

This article investigates the determinants of repeat migration among the 44 regions of Canada, using information from a large micro-database which spans the period 1968 to 1971. The explanation of repeat migration probabilities is a difficult task, and this attempt is only partly successful. May of the explanatory variables are not significant, and the overall explanatory power of the equations is not high. In the area of personal characteristics, the variables related to age, sex, and marital status are generally significant and with expected signs. The distance variable has a strongly positive effect on onward move probabilities. Variables related to prior migration experience have an important impact that differs between return and onward probabilities. In particular, the occurrence of prior moves has a striking effect on the probability of onward migration. The variable representing disappointment, or relative success of the initial move, plays a significant role in explaining repeat migration probabilities. The disappointment variable represents the ratio of actural versus expected wage income in the year after the initial move, and its effect on both repeat migration probabilities is always negative and almost always highly significant. The repeat probabilities diminish after a year's stay in the destination region, but disappointment in the most recent year still has a bearing on the delayed repeat probabilities. While the quantitative impact of the disappointment variable is not large, it is difficult to draw comparisons since similar estimates are not available elsewhere.

Repeated measures of body mass index and C-reactive protein in relation to all-cause mortality and cardiovascular disease

DEFF Research Database (Denmark)

O'Doherty, Mark G; Jørgensen, Torben; Borglykke, Anders

2014-01-01

Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single 'baseline' measurement and such analyses cannot account for possible changes in these which...... may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between......, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity....

How can HR practices support front-end innovation and increase the innovativeness of companies?

DEFF Research Database (Denmark)

Aagaard, Annabeth; Andersen, Torben

2014-01-01

to be reinterpreted in a context of heterogeneity and polyvalence. Finally performance management and talent management should play a greater role in emphasising exclusive values and rational goal-oriented behaviour among employees, compared to the more inclusive mainstream values that characterise much HRM......' innovativeness. If HR is to support these activities, focus should be on broader issues such as team-based organising, founded on a questioning attitude and a management style with a high level of empowerment. In addition, traditional HR themes such as recruitment, training and development have...

Conformational dynamics and ligand binding in the multi-domain protein PDC109.

Directory of Open Access Journals (Sweden)

Hyun Jin Kim

2010-02-01

Full Text Available PDC109 is a modular multi-domain protein with two fibronectin type II (Fn2 repeats joined by a linker. It plays a major role in bull sperm binding to the oviductal epithelium through its interactions with phosphorylcholines (PhCs, a head group of sperm cell membrane lipids. The crystal structure of the PDC109-PhC complex shows that each PhC binds to the corresponding Fn2 domain, while the two domains are on the same face of the protein. Long timescale explicit solvent molecular dynamics (MD simulations of PDC109, in the presence and absence of PhC, suggest that PhC binding strongly correlates with the relative orientation of choline-phospholipid binding sites of the two Fn2 domains; unless the two domains tightly bind PhCs, they tend to change their relative orientation by deforming the flexible linker. The effective PDC109-PhC association constant of 28 M(-1, estimated from their potential of mean force is consistent with the experimental result. Principal component analysis of the long timescale MD simulations was compared to the significantly less expensive normal mode analysis of minimized structures. The comparison indicates that difference between relative domain motions of PDC109 with bound and unbound PhC is captured by the first principal component in the principal component analysis as well as the three lowest normal modes in the normal mode analysis. The present study illustrates the use of detailed MD simulations to clarify the energetics of specific ligand-domain interactions revealed by a static crystallographic model, as well as their influence on relative domain motions in a multi-domain protein.

Quantum repeated games revisited

International Nuclear Information System (INIS)

Frąckiewicz, Piotr

2012-01-01

We present a scheme for playing quantum repeated 2 × 2 games based on Marinatto and Weber’s approach to quantum games. As a potential application, we study the twice repeated Prisoner’s Dilemma game. We show that results not available in the classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games proposed by Iqbal and Toor. We point out the drawbacks that make their results unacceptable. (paper)

Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms.

Science.gov (United States)

Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desirée; Forrest, Lucy R

2015-01-01

Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called "repeat-swap modeling" to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that nucleoside transport also

Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms

Directory of Open Access Journals (Sweden)

Cristina eFenollar Ferrer

2015-09-01

Full Text Available Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to either the outside or inside of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (asymmetry of these systems has been successfully used as a bioinformatic tool, called repeat-swap modeling to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that

Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41.

Directory of Open Access Journals (Sweden)

Charles Sabin

Full Text Available The human monoclonal antibody (mAb HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1 of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool.

Transcription instability in high-risk neuroblastoma is associated with a global perturbation of chromatin domains.

Science.gov (United States)

Zanon, Carlo; Tonini, Gian Paolo

2017-11-01

Chromosome instability has a pivotal role among the hallmarks of cancer, but its transcriptional counterpart is rarely considered a relevant factor in cell destabilization. To examine transcription instability (TIN), we first devised a metric we named TIN index and used it to evaluate TIN on a dataset containing more than 500 neuroblastoma samples. We found that metastatic tumors from high-risk (HR) patients are characterized by significantly different TIN index values compared to low/intermediate-risk patients. Our results indicate that the TIN index is a good predictor of neuroblastoma patient's outcome, and a related TIN index gene signature (TIN-signature) is also able to predict the neuroblastoma patient's outcome with high confidence. Interestingly, we find that TIN-signature genes have a strong positional association with superenhancers in neuroblastoma tumors. Finally, we show that TIN is linked to chromatin structural domains and interferes with their integrity in HR neuroblastoma patients. This novel approach to gene expression analysis broadens the perspective of genome instability investigations to include functional aspects. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

HR-MAS NMR allied to chemometric on Hancornia speciosa varieties differentiation

Energy Technology Data Exchange (ETDEWEB)

Flores, Igor S. [Instituto Federal de Goiás (IFG), Luziânia, GO (Brazil); Silva, Andressa K.; Chaves, Lazaro J.; Collevatti, Rosane G.; Lião, Luciano M., E-mail: lucianoliao@ufg.br [Universidade Federal de Goiás (UFG), Goiânia, GO (Brazil); Furquim, Leonnardo C. [Faculdade Objetivo, GO (Brazil); Castro, Carlos F.S. [Instituto Federal de Educação, Ciência e Tecnologia Goiano (IFGoiano), GO (Brazil)

2018-05-01

This work describes the potential of chemometric analyses applied to {sup 1}H high-resolution magic angle spinning nuclear magnetic resonance ({sup 1}H HR-MAS NMR) data for the chemotaxonomic investigation of Hancornia speciosa (Apocynaceae) varieties. This plant, popularly known as mangaba, has a complex morphological differentiation and thus chemical analyses can be used for their taxonomic classification. In comparison to traditional techniques, {sup 1}H HR-MAS NMR allied with chemometrics provided a simple and low cost method for chemotaxonomy. Leaves of four varieties of H. speciosa from a common garden experiment was studied and demonstrated that H. speciosa var. speciosa differs from others due to its specific metabolic profile, and var. pubescens was discriminated based on its high phenolic compound content. The distinction between the latter variety and gardineri is important once it allows for the selection of samples with greater commercial value, once they produce the largest and heaviest fruits. (author)

The evolution of the DLK1-DIO3 imprinted domain in mammals.

Directory of Open Access Journals (Sweden)

Carol A Edwards

2008-06-01

Full Text Available A comprehensive, domain-wide comparative analysis of genomic imprinting between mammals that imprint and those that do not can provide valuable information about how and why imprinting evolved. The imprinting status, DNA methylation, and genomic landscape of the Dlk1-Dio3 cluster were determined in eutherian, metatherian, and prototherian mammals including tammar wallaby and platypus. Imprinting across the whole domain evolved after the divergence of eutherian from marsupial mammals and in eutherians is under strong purifying selection. The marsupial locus at 1.6 megabases, is double that of eutherians due to the accumulation of LINE repeats. Comparative sequence analysis of the domain in seven vertebrates determined evolutionary conserved regions common to particular sub-groups and to all vertebrates. The emergence of Dlk1-Dio3 imprinting in eutherians has occurred on the maternally inherited chromosome and is associated with region-specific resistance to expansion by repetitive elements and the local introduction of noncoding transcripts including microRNAs and C/D small nucleolar RNAs. A recent mammal-specific retrotransposition event led to the formation of a completely new gene only in the eutherian domain, which may have driven imprinting at the cluster.

Single and 2-week repeated intravenous dose toxicity studies of disodium mercaptoundecahydro-closo-dodecaborate in rats

Energy Technology Data Exchange (ETDEWEB)

Itoh, Fumio; Yabuuchi, Kazuya; Ohno, Kouji; Muraoka, Yoshihiro [Shionogi and Co. Ltd., Toyonaka, Osaka (Japan). Developmental Research Lab.; Ikeuchi, Isao

1998-10-01

Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day. (author)

A Novel Sub-pixel Measurement Algorithm Based on Mixed the Fractal and Digital Speckle Correlation in Frequency Domain

Directory of Open Access Journals (Sweden)

Zhangfang Hu

2014-10-01

Full Text Available The digital speckle correlation is a non-contact in-plane displacement measurement method based on machine vision. Motivated by the facts that the low accuracy and large amount of calculation produced by the traditional digital speckle correlation method in spatial domain, we introduce a sub-pixel displacement measurement algorithm which employs a fast interpolation method based on fractal theory and digital speckle correlation in frequency domain. This algorithm can overcome either the blocking effect or the blurring caused by the traditional interpolation methods, and the frequency domain processing also avoids the repeated searching in the correlation recognition of the spatial domain, thus the operation quantity is largely reduced and the information extracting speed is improved. The comparative experiment is given to verify that the proposed algorithm in this paper is effective.

24 hr non-invasive ambulatory blood pressure and heart rate monitoring in Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Eva eStübner

2013-05-01

Full Text Available Non-motor symptoms are now commonly recognized in Parkinson’s Disease (PD and can include dysautonomia. Impairment of cardiovascular autonomic function can occur at any stage of PD but is typically prevalent in advanced stages or related to (anti-parkinsonian drugs and can result in atypical blood pressure (BP readings and related symptoms such as orthostatic hypotension (OH and supine hypertension. OH is usually diagnosed with a head-up-tilt test (HUT or an (active standing test (also known as Schellong test in the laboratory, but 24 hour Ambulatory Blood Pressure Monitoring (ABPM in a home setting may have several advantages, such as providing an overview of symptoms in daily life alongside pathophysiology as well as assessment of treatment interventions. This, however, is only possible if ABPM is administrated correctly and an autonomic protocol (including a diary is followed. which will be discussed in this review. A 24hr ABPM does not only allow the detection of OH, if it is present, but also the assessment of cardiovascular autonomic dysfunction during and after various daily stimuli, such as postprandial and alcohol dependent hypotension, as well as exercise and drug induced hypotension. Furthermore, information about the circadian rhythm of BP and heart rate (HR can be obtained and establish whether or not a patient has a fall of BP at night (i.e. ‘dipper’ vs. non-‘dipper’. The information about nocturnal BP may also allow the investigation or detection of disorders such as sleep dysfunction, nocturnal movement disorders and obstructive sleep apnea, which are common in PD. Additionally, a 24hr ABPM should be conducted to examine the effectiveness of OH therapy. This review will outline the methodology of 24 hr ABPM in PD, summarize findings of such studies in PD and briefly consider common daily stimuli that might affect 24 Hr ABPM.

THE CHARA ARRAY ANGULAR DIAMETER OF HR 8799 FAVORS PLANETARY MASSES FOR ITS IMAGED COMPANIONS

International Nuclear Information System (INIS)

Baines, Ellyn K.; White, Russel J.; Jones, Jeremy; Boyajian, Tabetha; McAlister, Harold A.; Ten Brummelaar, Theo A.; Turner, Nils H.; Sturmann, Judit; Sturmann, Laszlo; Goldfinger, P. J.; Farrington, Christopher D.; Riedel, Adric R.; Huber, Daniel; Ireland, Michael; Von Braun, Kaspar; Ridgway, Stephen T.

2012-01-01

HR 8799 is an hF0 mA5 γ Doradus-, λ Bootis-, Vega-type star best known for hosting four directly imaged candidate planetary companions. Using the CHARA Array interferometer, we measure HR 8799's limb-darkened angular diameter to be 0.342 ± 0.008 mas (an error of only 2%). By combining our measurement with the star's parallax and photometry from the literature, we greatly improve upon previous estimates of its fundamental parameters, including stellar radius (1.44 ± 0.06 R ☉ ), effective temperature (7193 ± 87 K, consistent with F0), luminosity (5.05 ± 0.29 L ☉ ), and the extent of the habitable zone (HZ; 1.62-3.32 AU). These improved stellar properties permit much more precise comparisons with stellar evolutionary models, from which a mass and age can be determined, once the metallicity of the star is known. Considering the observational properties of other λ Bootis stars and the indirect evidence for youth of HR 8799, we argue that the internal abundance, and what we refer to as the effective abundance, is most likely near solar. Finally, using the Yonsei-Yale evolutionary models with uniformly scaled solar-like abundances, we estimate HR 8799's mass and age considering two possibilities: 1.516 +0.038 –0.024 M ☉ and 33 +7 –13.2 Myr if the star is contracting toward the zero-age main sequence or 1.513 +0.023 –0.024 M ☉ and 90 +381 –50 Myr if it is expanding from it. This improved estimate of HR 8799's age with realistic uncertainties provides the best constraints to date on the masses of its orbiting companions, and strongly suggests they are indeed planets. They nevertheless all appear to orbit well outside the HZ of this young star.

Screening for high risk human papilloma virus (HR-HPV) subtypes, among Sudanese patients with oral lesions.

Science.gov (United States)

Babiker, Ali Yousif; Eltom, Faris Margani; Abdalaziz, Mohamed S; Rahmani, Arshad; Abusail, Saadalnour; Ahmed, Hussain Gadelkareem

2013-01-01

HR-HPV subtypes are strongly linked to etiology of many human cancers including oral cancer. The epidemiology of infection with different HPV genotypes greatly varies in different countries. The aim of this study was to identify and genotype the HR-HPV subtypes in oral tissues obtained from Sudanese patients with oral lesions. In this retrospective study 200 patients with oral lesions were screened by molecular methods (PCR) for the presence of HR-HPV subtypes. Of the 200 patients, 100/200 were patients with oral cancer (ascertained as case group) and 100/200 were patients with non-neoplastic oral lesions (ascertained as control group). Out of the 200 patients, 12/200 (6%) were found with HR-HPV infection. Of the 12 positive patients, 8/12 (66.7%) were among cases and the remaining 4/12 (33.3%) were among control group. The distribution of different genotypes was: type HPV 16 6/12 (50%), HPV18 4/12 (34%), HPV 31 1/12 (8%) and HPV 33 1/12 (8%). In view of these findings, HPV particularly subtypes 16 and 18 play a role in the etiology of oral cancer in the Sudan.

Intelligence and Information-Sharing Elements of S.4 and H.R. 1

National Research Council Canada - National Science Library

Masse, Todd

2007-01-01

Title I of S.4 and Title VII of H.R. 1 include corresponding measures related to enhancing information and intelligence sharing, both horizontally within the Federal Government and vertically between the Federal Government and state...

Thrombospondin-1 type 1 repeats in a model of inflammatory bowel disease: transcript profile and therapeutic effects.

Directory of Open Access Journals (Sweden)

Zenaida P Lopez-Dee

Full Text Available Thrombospondin-1 (TSP-1 is a matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To ascertain possible functions and evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and microarray analyses on a mouse model of induced colitis. We used dextran sulfate sodium (DSS to induce colitis in wild-type (WT mice for 7 days. Simultaneously, mice were injected with either saline or one form of TSP-1 derived recombinant proteins, containing either (1 the three type 1 repeats of the TSP-1 (3TSR, (2 the second type 1 repeat (TSR2, or (3 TSR2 with the RFK sequence (TSR2+RFK. Total RNA isolated from the mice colons were processed and hybridized to mouse arrays. Array data were validated by real-time qPCR and immunohistochemistry. Histological and disease indices reveal that the mice treated with the TSRs show different patterns of leukocytic infiltration and that 3TSR treatment was the most effective in decreasing inflammation in DSS-induced colitis. Transcriptional profiling revealed differentially expressed (DE genes, with the 3TSR-treated mice showing the least deviation from the WT-water controls. In conclusion, this study shows that 3TSR treatment is effective in attenuating the inflammatory response to DSS injury. In addition, the transcriptomics work unveils novel genetic data that suggest beneficial application of the TSR domains in inflammatory bowel disease.

Domains and domain loss

DEFF Research Database (Denmark)

Haberland, Hartmut

2005-01-01

politicians and in the media, especially in the discussion whether some languages undergo ‘domain loss’ vis-à-vis powerful international languages like English. An objection that has been raised here is that domains, as originally conceived, are parameters of language choice and not properties of languages...

Lifetime validation of high-reliability (>30,000hr) rotary cryocoolers for specific customer profiles

Science.gov (United States)

Cauquil, Jean-Marc; Seguineau, Cédric; Vasse, Christophe; Raynal, Gaetan; Benschop, Tonny

2018-05-01

The cooler reliability is a major performance requested by the customers, especially for 24h/24h applications, which are a growing market. Thales has built a reliability policy based on accelerate ageing and tests to establish a robust knowledge on acceleration factors. The current trend seems to prove that the RM2 mean time to failure is now higher than 30,000hr. Even with accelerate ageing; the reliability growth becomes hardly manageable for such large figures. The paper focuses on these figures and comments the robustness of such a method when projections over 30,000hr of MTTF are needed.

Repeatability of visual acuity measurement.

Science.gov (United States)

Raasch, T W; Bailey, I L; Bullimore, M A

1998-05-01

This study investigates features of visual acuity chart design and acuity testing scoring methods which affect the validity and repeatability of visual acuity measurements. Visual acuity was measured using the Sloan and British Standard letter series, and Landolt rings. Identifiability of the different letters as a function of size was estimated, and expressed in the form of frequency-of-seeing curves. These functions were then used to simulate acuity measurements with a variety of chart designs and scoring criteria. Systematic relationships exist between chart design parameters and acuity score, and acuity score repeatability. In particular, an important feature of a chart, that largely determines the repeatability of visual acuity measurement, is the amount of size change attributed to each letter. The methods used to score visual acuity performance also affect repeatability. It is possible to evaluate acuity score validity and repeatability using the statistical principles discussed here.

Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

Directory of Open Access Journals (Sweden)

Zomaya Albert Y

2006-12-01

Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

A 170kDa multi-domain cystatin of Fasciola gigantica is active in the male reproductive system.

Science.gov (United States)

Geadkaew, Amornrat; Kosa, Nanthawat; Siricoon, Sinee; Grams, Suksiri Vichasri; Grams, Rudi

2014-09-01

Cystatins are functional as intra- and extracellular inhibitors of cysteine proteases and are expressed as single or multi-domain proteins. We have previously described two single domain type 1 cystatins in the trematode Fasciola gigantica that are released into the parasite's intestinal tract and exhibit inhibitory activity against endogenous and host cathepsin L and B proteases. In contrast, the here presented 170kDa multi-domain cystatin (FgMDC) comprises signal peptide and 12 tandem repeated cystatin-like domains with similarity to type 2 single domain cystatins. The domains show high sequence divergence with identity values often 120kDa molecular mass in immunoblots of parasite crude extracts and ES product with different banding patterns for each antiserum demonstrating complex processing of the proprotein. The four domains with the highest conserved QVVAG motifs were expressed in Escherichia coli and the refolded recombinant proteins blocked cysteine protease activity in the parasite's ES product. Strikingly, immunohistochemical analysis using seven domain-specific antisera localized FgMDC in testis lobes and sperm. It is speculated that the processed cystatin-like domains have function analogous to the mammalian group of male reproductive tissue-specific type 2 cystatins and are functional in spermiogenesis and fertilization. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural analysis of poly-SUMO chain recognition by the RNF4-SIMs domain.

Science.gov (United States)

Kung, Camy C-H; Naik, Mandar T; Wang, Szu-Huan; Shih, Hsiu-Ming; Chang, Che-Chang; Lin, Li-Ying; Chen, Chia-Lin; Ma, Che; Chang, Chi-Fon; Huang, Tai-Huang

2014-08-15

The E3 ubiquitin ligase RNF4 (RING finger protein 4) contains four tandem SIM [SUMO (small ubiquitin-like modifier)-interaction motif] repeats for selective interaction with poly-SUMO-modified proteins, which it targets for degradation. We employed a multi-faceted approach to characterize the structure of the RNF4-SIMs domain and the tetra-SUMO2 chain to elucidate the interaction between them. In solution, the SIM domain was intrinsically disordered and the linkers of the tetra-SUMO2 were highly flexible. Individual SIMs of the RNF4-SIMs domains bind to SUMO2 in the groove between the β2-strand and the α1-helix parallel to the β2-strand. SIM2 and SIM3 bound to SUMO with a high affinity and together constituted the recognition module necessary for SUMO binding. SIM4 alone bound to SUMO with low affinity; however, its contribution to tetra-SUMO2 binding avidity is comparable with that of SIM3 when in the RNF4-SIMs domain. The SAXS data of the tetra-SUMO2-RNF4-SIMs domain complex indicate that it exists as an ordered structure. The HADDOCK model showed that the tandem RNF4-SIMs domain bound antiparallel to the tetra-SUMO2 chain orientation and wrapped around the SUMO protamers in a superhelical turn without imposing steric hindrance on either molecule.

The extracellular protein factor Epf from Streptococcus pyogenes is a cell surface adhesin that binds to cells through an N-terminal domain containing a carbohydrate-binding module.

Science.gov (United States)

Linke, Christian; Siemens, Nikolai; Oehmcke, Sonja; Radjainia, Mazdak; Law, Ruby H P; Whisstock, James C; Baker, Edward N; Kreikemeyer, Bernd

2012-11-02

Streptococcus pyogenes is an exclusively human pathogen. Streptococcal attachment to and entry into epithelial cells is a prerequisite for a successful infection of the human host and requires adhesins. Here, we demonstrate that the multidomain protein Epf from S. pyogenes serotype M49 is a streptococcal adhesin. An epf-deficient mutant showed significantly decreased adhesion to and internalization into human keratinocytes. Cell adhesion is mediated by the N-terminal domain of Epf (EpfN) and increased by the human plasma protein plasminogen. The crystal structure of EpfN, solved at 1.6 Å resolution, shows that it consists of two subdomains: a carbohydrate-binding module and a fibronectin type III domain. Both fold types commonly participate in ligand receptor and protein-protein interactions. EpfN is followed by 18 repeats of a domain classified as DUF1542 (domain of unknown function 1542) and a C-terminal cell wall sorting signal. The DUF1542 repeats are not involved in adhesion, but biophysical studies show they are predominantly α-helical and form a fiber-like stalk of tandem DUF1542 domains. Epf thus conforms with the widespread family of adhesins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), in which a cell wall-attached stalk enables long range interactions via its adhesive N-terminal domain.

Examination of the fine interstitial changes of pneumoconiosis with high resolution computed tomography (HR-CT)

International Nuclear Information System (INIS)

Kido, Masamitsu; Miyazaki, Nobuyoshi; Harada, Susumu; Nakata, Hajime

1986-01-01

High resolution CT was performed in 14 patients with fine interstitial changes of pneumoconiosis and Review image was evaluated for the diagnostic accuracy as compared with conventional chest roentgenogram. Of the 14 Patients in the study, 7 were divided category 1 by the ILO U/C classification, 4 were category 2, 3 were category 3. Studies of lung function showed obstructive ventilatory disturbance characterized by moderate reduction in FEV 1.0% (58.6 ± 16.5 %) and V25/H (0.34 ± 0.24 l/sec/m). HR-CT defined more sensitive in the presence of fine lung nodules than conventional X-p, and showed high contrast interfaces provided by the aerated lung. HR-CT was also of value in detecting bulla, bleb, peripleural changes and hilar lymphadenopathy. Radiologic-pathologic correlation was examined on tne specimens of transbronchial lung biopsy in 4 patients, and revealed the diagnostic usefullness of HR-CT. (author)

ATTITUDE ASSESSMENT USING PLEIADES-HR CAPABILITIES

Directory of Open Access Journals (Sweden)

J. M. Delevit

2012-07-01

Full Text Available Since SPOT1, the French national space centre (CNES has worked on improving the geometry of Earth observation spacecrafts. The accuracy of sensor calibration is one of the main key points for any Earth observation application such as orthorectification, DEM generation or surface change detection. For the last twenty years CNES has developed two families of methods: absolute methods and relative methods. These methods are used to characterize a pushbroom acquisition along the detector line and the time line. By this way, the viewing directions are measured and the residual of the spacecraft’s attitude angles (not restituted by the Attitude and Orbit Control System is estimated. This information can complete the geometric model of all the scenes acquired by the instrument and is used in all geometric applications. This paper presents new attitude assessment methods taking advantage of the capabilities of Pléiades-HR in terms of agility and focal plane arrangement – panchromatic band and multispectral (MS bands.

Getting used to academic public speaking: global self-esteem predicts habituation in blood pressure response to repeated thesis presentations.

Science.gov (United States)

Elfering, Achim; Grebner, Simone

2012-06-01

Global self-esteem was tested to predict quicker cardiovascular adaptation during stressful oral thesis presentation and faster habituation from the first to the second and third thesis presentations. Nineteen graduate students initially rated their global self-esteem and afterwards orally presented their theses proposals in 20-min presentations to their thesis supervisor and peers. A second and third presentation of the revised thesis concepts took place at 4-weeks intervals. Ambulatory blood pressure and heart rate were assessed repeatedly during the presentations. Post-talk self ratings of stressfulness indicated presentations to be a strong public speaking stressor. One hundred and thirty-eight measurements of systolic (SBP), diastolic blood pressure (DBP), and heart rate (HR) showed a significant adaptation (decrease) during presentations. There was an overall mean level decrease from the first to the second, and the second to the third presentations in HR, but not in SBP and DBP. However, habituation in SBP and DBP across three presentations was significantly faster (p < .05) in those participants who initially reported higher levels of global self-esteem. Higher global self-esteem did not foster adaptation within the presentations. Self-esteem is discussed as an important individual resource that allows successful coping with recurring evaluative threats.

HR Technology Tools: Less Time on Paper and More on People

Science.gov (United States)

Tillman, Tom

2009-01-01

Many human resource managers face a dilemma. They would like to spend more time improving the overall work environment for employees. They want to help their executives save on workforce-related expenses, find and hire better talent, and improve existing talent through training and development. Unfortunately, most days, HR managers are stuck doing…

The energy landscapes of repeat-containing proteins: topology, cooperativity, and the folding funnels of one-dimensional architectures.

Directory of Open Access Journals (Sweden)

Diego U Ferreiro

2008-05-01

Full Text Available Repeat-proteins are made up of near repetitions of 20- to 40-amino acid stretches. These polypeptides usually fold up into non-globular, elongated architectures that are stabilized by the interactions within each repeat and those between adjacent repeats, but that lack contacts between residues distant in sequence. The inherent symmetries both in primary sequence and three-dimensional structure are reflected in a folding landscape that may be analyzed as a quasi-one-dimensional problem. We present a general description of repeat-protein energy landscapes based on a formal Ising-like treatment of the elementary interaction energetics in and between foldons, whose collective ensemble are treated as spin variables. The overall folding properties of a complete "domain" (the stability and cooperativity of the repeating array can be derived from this microscopic description. The one-dimensional nature of the model implies there are simple relations for the experimental observables: folding free-energy (DeltaG(water and the cooperativity of denaturation (m-value, which do not ordinarily apply for globular proteins. We show how the parameters for the "coarse-grained" description in terms of foldon spin variables can be extracted from more detailed folding simulations on perfectly funneled landscapes. To illustrate the ideas, we present a case-study of a family of tetratricopeptide (TPR repeat proteins and quantitatively relate the results to the experimentally observed folding transitions. Based on the dramatic effect that single point mutations exert on the experimentally observed folding behavior, we speculate that natural repeat proteins are "poised" at particular ratios of inter- and intra-element interaction energetics that allow them to readily undergo structural transitions in physiologically relevant conditions, which may be intrinsically related to their biological functions.

A diverse host thrombospondin-type-1 repeat protein repertoire promotes symbiont colonization during establishment of cnidarian-dinoflagellate symbiosis.

Science.gov (United States)

Neubauer, Emilie-Fleur; Poole, Angela Z; Neubauer, Philipp; Detournay, Olivier; Tan, Kenneth; Davy, Simon K; Weis, Virginia M

2017-05-08

The mutualistic endosymbiosis between cnidarians and dinoflagellates is mediated by complex inter-partner signaling events, where the host cnidarian innate immune system plays a crucial role in recognition and regulation of symbionts. To date, little is known about the diversity of thrombospondin-type-1 repeat (TSR) domain proteins in basal metazoans or their potential role in regulation of cnidarian-dinoflagellate mutualisms. We reveal a large and diverse repertoire of TSR proteins in seven anthozoan species, and show that in the model sea anemone Aiptasia pallida the TSR domain promotes colonization of the host by the symbiotic dinoflagellate Symbiodinium minutum . Blocking TSR domains led to decreased colonization success, while adding exogenous TSRs resulted in a 'super colonization'. Furthermore, gene expression of TSR proteins was highest at early time-points during symbiosis establishment. Our work characterizes the diversity of cnidarian TSR proteins and provides evidence that these proteins play an important role in the establishment of cnidarian-dinoflagellate symbiosis.

Fostering repeat donations in Ghana.

Science.gov (United States)

Owusu-Ofori, S; Asenso-Mensah, K; Boateng, P; Sarkodie, F; Allain, J-P

2010-01-01

Most African countries are challenged in recruiting and retaining voluntary blood donors by cost and other complexities and in establishing and implementing national blood policies. The availability of replacement donors who are a cheaper source of blood has not enhanced repeat voluntary donor initiatives. An overview of activities for recruiting and retaining voluntary blood donors was carried out. Donor records from mobile sessions were reviewed from 2002 to 2008. A total of 71,701 blood donations; 45,515 (63.5%) being voluntary donations with 11,680 (25%) repeat donations were collected during the study period. Donations from schools and colleges contributed a steady 60% of total voluntary whilst radio station blood drives increased contribution from 10 to 27%. Though Muslim population is less than 20%, blood collection was above the 30-donation cost-effectiveness threshold with a repeat donation trend reaching 60%. In contrast Christian worshippers provided donations. Repeat donation trends amongst school donors and radio blood drives were 20% and 70% respectively. Repeat donations rates have been variable amongst different blood donor groups in Kumasi, Ghana. The impact of community leaders in propagating altruism cannot be overemphasized. Programs aiming at motivating replacement donors to be repeat donors should be developed and assessed. Copyright 2009 The International Association for Biologicals. All rights reserved.

P/2006 HR30 (Siding Spring): A Low-activity Comet in Near-Earth Space

Science.gov (United States)

Hicks, Michael D.; Bauer, James M.

2007-01-01

The low cometary activity of P/2006 HR30 (Siding Spring) allowed a unique opportunity to study the nucleus of a periodic comet while near perihelion. P/2006 HR30 was originally targeted as a potential extinct comet, and we measured spectral reflectance and dust production using long-slit CCD spectroscopy and wide-field imaging obtained at the Palomar Mountain 200 inch telescope on 2006 August 3 and 4. The dust production Afp = 19.7 +/- 0.4 cm and mass-loss rate Q(dust) 4.1 +/- 0.1 kg/sec of the comet were approximately 2 orders of magnitude dust less than 1P/Halley at similar heliocentric distance. The VRI colors derived from the spectral reflectance were compared to Kuiper Belt objects, Centaurs, and other cometary nuclei. We found that the spectrum of P/2006 HR30 was consistent with other comets. However, the outer solar system bodies have a color distribution statistically distinct from cometary nuclei. It is our conjecture that cometary activity, most likely the reaccretion of ejected cometary dust, tends to moderate and mute the visible colors of the surface of cometary nuclei.

Deletion in the first cysteine-rich repeat of low density lipoprotein receptor impairs its transport but not lipoprotein binding in fibroblasts from a subject with familial hypercholesterolemia

International Nuclear Information System (INIS)

Leitersdorf, E.; Hobbs, H.H.; Fourie, A.M.; Jacobs, M.; Van Der Westhuyzen, D.R.; Coetzee, G.A.

1988-01-01

The ligand-binding domain of the low density lipoprotein (LDL) receptor is composed of seven cysteine-rich repeats, each ∼ 40 amino acids long. Previous studies showed that if the first repeat of the ligand-binding domain (encoded by exon 2) is deleted, the receptor fails to bind an anti-LDL receptor monoclonal antibody (IgG-C7) but continues to bind LDL with high affinity. Cultured fibroblasts from a Black South African Xhosa patient (TT) with the clinical syndrome of homozygous familial hypercholesterolemia demonstrated high-affinity cell-surface binding of 125 I-labeled LDL but not 125 I-labeled IgG-C7. previous haplotype analysis, using 10 restriction fragment length polymorphic sites, suggested that the patient inherited two identical LDL receptor alleles. The polymerase chain reaction technique was used to selectively amplify exon 2 of the LDL receptor gene from this patient. Sequence analysis of the amplified fragment disclosed a deletion of six base pairs that removes two amino acids, aspartic acid and glycine, from the first cysteine-rich ligand binding repeat. The mutation creates a new Pst I restriction site that can be used to detect the deletion. The existence of this mutant allele confirms that the epitope of IgG-C7 is located in the first cysteine-rich repeat and that this repeat is not necessary for LDL binding. The mutant gene produced a normally sized 120-kilodalton LDL receptor precursor protein that matured to the 160-kilodalton form at less than one-fourth the normal rate

Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains.

Science.gov (United States)

Keren, Ido; Klipcan, Liron; Bezawork-Geleta, Ayenachew; Kolton, Max; Shaya, Felix; Ostersetzer-Biran, Oren

2008-08-22

CRM (chloroplast RNA splicing and ribosome maturation) is a recently recognized RNA-binding domain of ancient origin that has been retained in eukaryotic genomes only within the plant lineage. Whereas in bacteria CRM domains exist as single domain proteins involved in ribosome maturation, in plants they are found in a family of proteins that contain between one and four repeats. Several members of this family with multiple CRM domains have been shown to be required for the splicing of specific plastidic group II introns. Detailed biochemical analysis of one of these factors in maize, CRS1, demonstrated its high affinity and specific binding to the single group II intron whose splicing it facilitates, the plastid-encoded atpF intron RNA. Through its association with two intronic regions, CRS1 guides the folding of atpF intron RNA into its predicted "catalytically active" form. To understand how multiple CRM domains cooperate to achieve high affinity sequence-specific binding to RNA, we analyzed the RNA binding affinity and specificity associated with each individual CRM domain in CRS1; whereas CRM3 bound tightly to the RNA, CRM1 associated specifically with a unique region found within atpF intron domain I. CRM2, which demonstrated only low binding affinity, also seems to form specific interactions with regions localized to domains I, III, and IV. We further show that CRM domains share structural similarities and RNA binding characteristics with the well known RNA recognition motif domain.

miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1

Energy Technology Data Exchange (ETDEWEB)

Liu, Shikai; Song, Lili, E-mail: commasll@163.com; Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

2015-04-17

Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3′-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. - Highlights: • miR-21 is highly expressed in HR-HPV (+) radioresistant cervical cancer patients. • miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells. • miR-21 can decrease radiation induced G2/M block and increase S phase accumulation. • miR-21 modulates radiosensitivity cervical cancer cell by directly targeting LATS1.

miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1

International Nuclear Information System (INIS)

Liu, Shikai; Song, Lili; Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

2015-01-01

Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3′-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. - Highlights: • miR-21 is highly expressed in HR-HPV (+) radioresistant cervical cancer patients. • miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells. • miR-21 can decrease radiation induced G2/M block and increase S phase accumulation. • miR-21 modulates radiosensitivity cervical cancer cell by directly targeting LATS1

Cervical cancer screening by high risk HPV testing in routine practice: results at one year recall of high risk HPV-positive and cytology-negative women.

Science.gov (United States)

Del Mistro, Annarosa; Frayle, Helena; Ferro, Antonio; Callegaro, Susanna; Del Sole, Annamaria; Stomeo, Anna; Cirillo, Emanuela; Fedato, Chiara; Pagni, Silvana; Barzon, Luisa; Zorzi, Manuel

2014-03-01

Cervical cancer screening by human papillomavirus (HPV) testing requires the use of additional triage and follow-up analyses. We evaluated women's compliance with and the performance of this strategy in a routine setting. Five cervical service screening programmes in North-East Italy. Eligible women aged 25-64 invited for a new screening episode underwent HPV testing for high risk types (hrHPV by Hybrid Capture 2) and cytology triage. Women with positive HPV and cytology results were referred for colposcopy; women with positive HPV but negative cytology results were referred to 1-year repeat hrHPV testing. Of 46,694 women screened by HPV testing up to December 2011, 3,211 (6.9%) tested hrHPV positive; 45% of these had a positive triage cytology. Those with negative cytology were invited for 1-yr repeat testing. Compliance with invitation was 61.6% at baseline and 85.3% at 1-yr repeat. Rate of persistent hrHPV positivity was 58% (830/1,435). Colposcopy performed in women with a positive hrHPV test at 1-yr repeat accounted for 36% of all colposcopies performed within the screening programmes. Cumulatively, a histological high-grade lesion was detected in 276 women (5.9‰ detection rate), 234 at baseline (85%), and 42 (15%) at 1-yr repeat. Compliance with hrHPV-based screening programmes was high both at baseline and at 1-yr repeat. Compared with the randomized trials, a higher proportion of triage cytology was read as positive, and only a small number of high-grade lesions were detected among the group of hrHPV positive cytology negative women who repeated testing 1-yr after baseline.

Human mismatch repair protein hMutLα is required to repair short slipped-DNAs of trinucleotide repeats.

Science.gov (United States)

Panigrahi, Gagan B; Slean, Meghan M; Simard, Jodie P; Pearson, Christopher E

2012-12-07

Mismatch repair (MMR) is required for proper maintenance of the genome by protecting against mutations. The mismatch repair system has also been implicated as a driver of certain mutations, including disease-associated trinucleotide repeat instability. We recently revealed a requirement of hMutSβ in the repair of short slip-outs containing a single CTG repeat unit (1). The involvement of other MMR proteins in short trinucleotide repeat slip-out repair is unknown. Here we show that hMutLα is required for the highly efficient in vitro repair of single CTG repeat slip-outs, to the same degree as hMutSβ. HEK293T cell extracts, deficient in hMLH1, are unable to process single-repeat slip-outs, but are functional when complemented with hMutLα. The MMR-deficient hMLH1 mutant, T117M, which has a point mutation proximal to the ATP-binding domain, is defective in slip-out repair, further supporting a requirement for hMLH1 in the processing of short slip-outs and possibly the involvement of hMHL1 ATPase activity. Extracts of hPMS2-deficient HEC-1-A cells, which express hMLH1, hMLH3, and hPMS1, are only functional when complemented with hMutLα, indicating that neither hMutLβ nor hMutLγ is sufficient to repair short slip-outs. The resolution of clustered short slip-outs, which are poorly repaired, was partially dependent upon a functional hMutLα. The joint involvement of hMutSβ and hMutLα suggests that repeat instability may be the result of aberrant outcomes of repair attempts.

Repeated DNA sequences in fungi

Energy Technology Data Exchange (ETDEWEB)

Dutta, S K

1974-11-01

Several fungal species, representatives of all broad groups like basidiomycetes, ascomycetes and phycomycetes, were examined for the nature of repeated DNA sequences by DNA:DNA reassociation studies using hydroxyapatite chromatography. All of the fungal species tested contained 10 to 20 percent repeated DNA sequences. There are approximately 100 to 110 copies of repeated DNA sequences of approximately 4 x 10/sup 7/ daltons piece size of each. Repeated DNA sequence homoduplexes showed on average 5/sup 0/C difference of T/sub e/50 (temperature at which 50 percent duplexes dissociate) values from the corresponding homoduplexes of unfractionated whole DNA. It is suggested that a part of repetitive sequences in fungi constitutes mitochondrial DNA and a part of it constitutes nuclear DNA. (auth)

Topological characteristics of helical repeat proteins

NARCIS (Netherlands)

Groves, M R; Barford, D

The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem

Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A following Acute Repeated Inhalation Exposure

Directory of Open Access Journals (Sweden)

Jenny R. Roberts

2014-01-01

Full Text Available Introduction Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. Methods The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m 3 , five hours per day, over nine work days, or filtered air (control. At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. Results No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following metha-choline (MCh inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP responses to these agents; however, the baseline heart rate (HR and HR responses to isoproterenol (ISO were significantly elevated at one-day post exposure

The immunoglobulin-like domains 1 and 2 of the protein tyrosine phosphatase LAR adopt an unusual horseshoe-like conformation

Science.gov (United States)

Biersmith, Bridget H.; Hammel, Michal; Geisbrecht, Erika R.; Bouyain, Samuel

2011-01-01

Neurogenesis depends on exquisitely regulated interactions between macromolecules on the cell surface and in the extracellular matrix. In particular, interactions between proteoglycans and members of the type IIa subgroup of receptor protein tyrosine phosphatases underlie critical developmental processes such as the formation of synapses at the neuromuscular junction and the migration of axons to their appropriate targets. We report here the crystal structures of the first and second immunoglobulin-like domains of the Drosophila type IIa receptor Dlar and its mouse homologue LAR. These two domains adopt an unusual antiparallel arrangement that has not been previously observed in tandem repeats of immunoglobulin-like domains and that is presumably conserved in all type IIa receptor protein tyrosine phosphatases. PMID:21402080

Nuclear licensing reform. Hearings before the Subcommittee on Energy and the Environment, House of Representatives, Ninety-Eighth Congress, First Session on H.R. 2511 and H.R. 2512, June 9 and 30, 1983

International Nuclear Information System (INIS)

Anon.

1984-01-01

Two bills (H.R. 2511 and H.R. 2512) amend licensing and siting regulations in the Atomic Energy Act by introducing the concept of one-stop licensing, encouraging standardized design and early site permits, and replacing adjudicatory proceedings with ''hybrid'' hearings. Witnesses speaking for and against the controversial proposals during the two-day hearing included Nunzio Palladino and other Commissioners of the Nuclear Regulatory Commission, Energy Secretary Hodel, and representatives of electric utilities, the nuclear industry, and environmental and public interest groups. Two appendices with additional material submitted for the hearing record follow the test of the two bills and the statements and testimony of 12 witnesses

Design criteria and design basis for the 100-HR-3 and 100-KR-4 pump-and-treat projects

International Nuclear Information System (INIS)

McKinley, W.S.; Winters, J.N.

1996-06-01

The 100-HR-3 and 100-KR-4 Operable Units are located in the 100 Area at the Hanford Site in Richland, Washington. The document describes the project objectives and design criteria to be used for the 100-HR-3 and 100-KR-4 groundwater pump-and-treat design activities

1H HR-MAS NMR and S180 cells: metabolite assignment and evaluation of pulse sequence

International Nuclear Information System (INIS)

Oliveira, Aline L. de; Martinelli, Bruno César B.; Lião, Luciano M.; Pereira, Flávia C.; Silveira-Lacerda, Elisangela P.; Alcantara, Glaucia B.

2014-01-01

High resolution magic angle spinning 1 H nuclear magnetic resonance spectroscopy (HR-MAS NMR) is a useful technique for evaluation of intact cells and tissues. However, optimal NMR parameters are crucial in obtaining reliable results. To identify the key steps for the optimization of HR-MAS NMR parameters, we assessed different pulse sequences and NMR parameters using sarcoma 180 (S180) cells. A complete assignment of the metabolites of S180 is given to assist future studies. (author)

High-resolution magnetic resonance imaging (HR-MRI) of the pleura and chest wall: Normal findings and pathological changes

International Nuclear Information System (INIS)

Bittner, R.C.; Schnoy, N.; Schoenfeld, N.; Grassot, A.; Loddenkemper, R.; Lode, H.; Kaiser, D.; Krumhaar, D.; Felix, R.

1995-01-01

To determine the value of high-resolution MRI in pleural and chest wall diseases, the normal and pathologic costal pleura and adjacent chest wall between paravertebral and the axillar region were examined with contrast enhanced high-resolution T 1 -weighted MRI images using a surface coil. Normal anatomy was evaluated in 5 healthy volunteers and a normal specimen of the thoracic wall, and correlation was made with corresponding HR-CT and histologic sections. CT-proved focal and diffuse changes of the pleura and the chest wall in 36 patients underwent HR-MRI, and visual comparison of MRI and CT was done retrospectively. Especially sagittal T 1 -weighted HR-MRI images allowed accurate delineation of the peripleural fat layer (PFL) and the innermost intercostal muscle (IIM), which served as landmarks of the intact inner chest wall. PFL and IIM were well delineated in 3/4 patients with tuberculous pleuritis, and in all 7 patients with non-specific pleuritis, as opposed to impairment of the PFL and/or the IIM, which was detected in 15/18 malignancies as a pattern of malignant chest wall involvement. In one case of tuberculous pleural empyema with edema of the inner chest wall HR-MRI produced false positive diagnosis of malignant disease. HR-MRI images improved non-invasive evaluation of pleural and chest wall diseases, and allowed for differentiation of bengin and malignant changes. (orig./MG) [de

The gap between research and practice: a replication study on the HR professionals' beliefs about effective human resource practices

NARCIS (Netherlands)

Sanders, Karin; van Riemsdijk, Maarten; Groen, B.A.C.

2008-01-01

In 2002 Rynes, Colbert and Brown asked human resource (HR) professionals to what extent they agreed with various HR research findings. Responses from 959 American participants showed that there are large discrepancies between research findings and practitioners' beliefs about effective human

10 MMBt/Hr AFBC Commercial Demonstration Cedar Lane Farms

Energy Technology Data Exchange (ETDEWEB)

Harold M. Keener; Mary H. Wicks; Tom Machamer; Dave Hoecke; Don Bonk; Bob Brown

2005-10-31

The objective of this project was to demonstrate and promote the commercialization of coal-fired atmospheric fluidized bed combustion (AFBC) systems, with limestone addition for SO2 emissions control and a baghouse for particulate emissions control. This AFBC system was targeted for small scale industrial-commercial-institutional space and process heat applications in the 4-40 MMBtu/hr size range. A cost effective and environmentally acceptable AFBC technology in this size range could displace a considerable amount of heating gas and oil with coal, while resulting in significant total cost savings to the owner/operators.

PRGPred: A platform for prediction of domains of resistance gene analogue (RGA in Arecaceae developed using machine learning algorithms

Directory of Open Access Journals (Sweden)

MATHODIYIL S. MANJULA

2015-12-01

Full Text Available Plant disease resistance genes (R-genes are responsible for initiation of defense mechanism against various phytopathogens. The majority of plant R-genes are members of very large multi-gene families, which encode structurally related proteins containing nucleotide binding site domains (NBS and C-terminal leucine rich repeats (LRR. Other classes possess' an extracellular LRR domain, a transmembrane domain and sometimes, an intracellular serine/threonine kinase domain. R-proteins work in pathogen perception and/or the activation of conserved defense signaling networks. In the present study, sequences representing resistance gene analogues (RGAs of coconut, arecanut, oil palm and date palm were collected from NCBI, sorted based on domains and assembled into a database. The sequences were analyzed in PRINTS database to find out the conserved domains and their motifs present in the RGAs. Based on these domains, we have also developed a tool to predict the domains of palm R-genes using various machine learning algorithms. The model files were selected based on the performance of the best classifier in training and testing. All these information is stored and made available in the online ‘PRGpred' database and prediction tool.

UK 2009-2010 repeat station report

Directory of Open Access Journals (Sweden)

Thomas J.G. Shanahan

2013-03-01

Full Text Available The British Geological Survey is responsible for conducting the UK geomagnetic repeat station programme. Measurements made at the UK repeat station sites are used in conjunction with the three UK magnetic observatories: Hartland, Eskdalemuir and Lerwick, to produce a regional model of the local field each year. The UK network of repeat stations comprises 41 stations which are occupied at approximately 3-4 year intervals. Practices for conducting repeat station measurements continue to evolve as advances are made in survey instrumentation and as the usage of the data continues to change. Here, a summary of the 2009 and 2010 UK repeat station surveys is presented, highlighting the measurement process and techniques, density of network, reduction process and recent results.

Teaching HR Professionals: The Classroom as a Community of Practice

Directory of Open Access Journals (Sweden)

Alex Avramenko

2013-05-01

Full Text Available This paper introduces an innovative course design incorporating both communities of practice and reflective practice as a learning strategy for part-time learners in higher education. The new design has been applied to teaching HR practitioners in a UK-based business school. Findings indicate that the suggested way of organizing teaching and learning for part-time professionals is very informative and facilitates a richer engagement with theory whilst addressing issues of practice.

Glaucoma diagnosis by mapping macula with Fourier domain optical coherence tomography

Science.gov (United States)

Tan, Ou; Lu, Ake; Chopra, Vik; Varma, Rohit; Hiroshi, Ishikawa; Schuman, Joel; Huang, David

2008-03-01

A new image segmentation method was developed to detect macular retinal sub-layers boundary on newly-developed Fourier-Domain Optical Coherence Tomography (FD-OCT) with macular grid scan pattern. The segmentation results were used to create thickness map of macular ganglion cell complex (GCC), which contains the ganglion cell dendrites, cell bodies and axons. Overall average and several pattern analysis parameters were defined on the GCC thickness map and compared for the diagnosis of glaucoma. Intraclass correlation (ICC) is used to compare the reproducibility of the parameters. Area under receiving operative characteristic curve (AROC) was calculated to compare the diagnostic power. The result is also compared to the output of clinical time-domain OCT (TD-OCT). We found that GCC based parameters had good repeatability and comparable diagnostic power with circumpapillary nerve fiber layer (cpNFL) thickness. Parameters based on pattern analysis can increase the diagnostic power of GCC macular mapping.

Structures of BIR domains from human NAIP and cIAP2.

Science.gov (United States)

Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

2009-11-01

The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1'-P4' side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3' position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2' and P4' pockets make similar interactions to those seen in other BIR domain-peptide complexes. The structures also reveal how a serine in the P1' position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins.

The more the better…or is it? The contradictory effects of HR practices on knowledge sharing motivation and behavior

NARCIS (Netherlands)

Andreeva, T.; Sergeeva, A.

2016-01-01

This article examines how individual-level antecedents such as motivation and ability to share knowledge mediate the relationship between HR practices and knowledge-sharing behaviour. The results of a survey of 329 secondary school teachers reveal the contradictory effects of different HR practices

Reject/repeat analysis and the effect prior film viewing has on a department's reject/repeat rate

International Nuclear Information System (INIS)

Clark, P.A.; Hogg, P.

2003-01-01

Purpose: Achieving cost-effectiveness within the NHS is an old initiative but one that has again been highlighted by recent government policies (The New NHS-Modern and Dependable, Stationary Office, London, 1997). It has been reiterated that it is the responsibility of individual Trusts to devise means to provide such a service. Reject/repeat analyses have long been the primary tool used to assess the cost-effectiveness of radiography departments (Quality Assurance in Diagnostic Radiology, WHO, Geneva, 1982). This research paper examines an in-house initiative (viewing patients' previous films) commonly employed in other Health Trusts in order to reduce departmental repeat/reject rates. Method: Three hundred orthopaedic patients with hip, knee and ankle prostheses were included in a reject/repeat analysis. The aim was to investigate whether or not viewing patient's previous relevant radiographs would be advantageous to the practicing radiographer. This was done through an audit cycle consisting of two audit periods each lasting for 3 months. The primary audit period recorded the baseline repeat/reject rate, with the secondary audit period recording the repeat/reject rate under an experimental condition of viewing the relevant radiographs. Results: The baseline audit revealed repeat rates of 33% in orthopaedic patients with hip, knee and ankle prostheses. The availability of prior film viewing to the radiographer reduced this repeat rate to 10.6%. Conclusion: Prior film viewing dramatically reduced the department's repeat/reject rate by 22.4%. This provides scope for significant patient dose reductions as well as reducing departmental film expenses. This is an underestimated initiative and should be used appropriately in routine clinical practice

The Extracellular Protein Factor Epf from Streptococcus pyogenes Is a Cell Surface Adhesin That Binds to Cells through an N-terminal Domain Containing a Carbohydrate-binding Module*

Science.gov (United States)

Linke, Christian; Siemens, Nikolai; Oehmcke, Sonja; Radjainia, Mazdak; Law, Ruby H. P.; Whisstock, James C.; Baker, Edward N.; Kreikemeyer, Bernd

2012-01-01

Streptococcus pyogenes is an exclusively human pathogen. Streptococcal attachment to and entry into epithelial cells is a prerequisite for a successful infection of the human host and requires adhesins. Here, we demonstrate that the multidomain protein Epf from S. pyogenes serotype M49 is a streptococcal adhesin. An epf-deficient mutant showed significantly decreased adhesion to and internalization into human keratinocytes. Cell adhesion is mediated by the N-terminal domain of Epf (EpfN) and increased by the human plasma protein plasminogen. The crystal structure of EpfN, solved at 1.6 Å resolution, shows that it consists of two subdomains: a carbohydrate-binding module and a fibronectin type III domain. Both fold types commonly participate in ligand receptor and protein-protein interactions. EpfN is followed by 18 repeats of a domain classified as DUF1542 (domain of unknown function 1542) and a C-terminal cell wall sorting signal. The DUF1542 repeats are not involved in adhesion, but biophysical studies show they are predominantly α-helical and form a fiber-like stalk of tandem DUF1542 domains. Epf thus conforms with the widespread family of adhesins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), in which a cell wall-attached stalk enables long range interactions via its adhesive N-terminal domain. PMID:22977243

The selection and adaptation of staff as the basis of the successful implementation of HR strategy

Directory of Open Access Journals (Sweden)

Vanicheva A.G.

2016-11-01

Full Text Available the article deals with questions of effective strategies of HR policy in the field of selection and adaptation of staff in the company. The text gives an information about effective methods of selection and adaptation, also it draws our attention to development of communication between employees. This paper can help to pay managers’ attention to effective selection and adaptation taking into consideration that introduction of a new employee to a position is responsible enough. Probably, first days in a new company are crucial for the system of motivation of HR policy in the development of HR strategy. Much attention is given to stages of adaptation for employee or chief executive.

Enzymatic amplification of a Y chromosome repeat in a single blastomere allows identification of the sex of preimplantation mouse embryos

International Nuclear Information System (INIS)

Bradbury, M.W.; Isola, L.M.; Gordon, J.W.

1990-01-01

The polymerase chain reaction (PCR) technique has been adapted to identify the sex of preimplantation mouse embryos rapidly. PCR was used to amplify a specific repeated DNA sequence on the Y chromosome from a single isolated blastomere in under 12 hr. The remainder of the biopsied embryo was then transferred to a pseudopregnant female and carried to term. Using this technique, 72% of embryos can be classed as potentially either male or female. Transfers of such embryos have produced pregnancies with 8/8 fetuses (100%) being of the predicted sex. Variations of the technique have demonstrated certain limitations to the present procedure as well as indicated possible strategies for improvement of the assay. The PCR technique may have wide application in the genetic analysis of preimplantation embryos

Repeating Marx

DEFF Research Database (Denmark)

Fuchs, Christian; Monticelli, Lara

2018-01-01

This introduction sets out the context of the special issue “Karl Marx @ 200: Debating Capitalism & Perspectives for the Future of Radical Theory”, which was published on the occasion of Marx’s bicentenary on 5 May 2018. First, we give a brief overview of contemporary capitalism’s development...... and its crises. Second, we argue that it is important to repeat Marx today. Third, we reflect on lessons learned from 200 years of struggles for alternatives to capitalism. Fourth, we give an overview of the contributions in this special issue. Taken together, the contributions in this special issue show...... that Marx’s theory and politics remain key inspirations for understanding exploitation and domination in 21st-century society and for struggles that aim to overcome these phenomena and establishing a just and fair society. We need to repeat Marx today....

Members of a novel protein family containing microneme adhesive repeat domains act as sialic acid-binding lectins during host cell invasion by apicomplexan parasites.

Science.gov (United States)

Friedrich, Nikolas; Santos, Joana M; Liu, Yan; Palma, Angelina S; Leon, Ester; Saouros, Savvas; Kiso, Makoto; Blackman, Michael J; Matthews, Stephen; Feizi, Ten; Soldati-Favre, Dominique

2010-01-15

Numerous intracellular pathogens exploit cell surface glycoconjugates for host cell recognition and entry. Unlike bacteria and viruses, Toxoplasma gondii and other parasites of the phylum Apicomplexa actively invade host cells, and this process critically depends on adhesins (microneme proteins) released onto the parasite surface from intracellular organelles called micronemes (MIC). The microneme adhesive repeat (MAR) domain of T. gondii MIC1 (TgMIC1) recognizes sialic acid (Sia), a key determinant on the host cell surface for invasion by this pathogen. By complementation and invasion assays, we demonstrate that TgMIC1 is one important player in Sia-dependent invasion and that another novel Sia-binding lectin, designated TgMIC13, is also involved. Using BLAST searches, we identify a family of MAR-containing proteins in enteroparasitic coccidians, a subclass of apicomplexans, including T. gondii, suggesting that all these parasites exploit sialylated glycoconjugates on host cells as determinants for enteric invasion. Furthermore, this protein family might provide a basis for the broad host cell range observed for coccidians that form tissue cysts during chronic infection. Carbohydrate microarray analyses, corroborated by structural considerations, show that TgMIC13, TgMIC1, and its homologue Neospora caninum MIC1 (NcMIC1) share a preference for alpha2-3- over alpha2-6-linked sialyl-N-acetyllactosamine sequences. However, the three lectins also display differences in binding preferences. Intense binding of TgMIC13 to alpha2-9-linked disialyl sequence reported on embryonal cells and relatively strong binding to 4-O-acetylated-Sia found on gut epithelium and binding of NcMIC1 to 6'sulfo-sialyl Lewis(x) might have implications for tissue tropism.

Chemical profile of beans cultivars (Phaseolus vulgaris) by 1H NMR - high resolution magic angle spinning (HR-MAS);Perfil quimico de cultivares de feijao (Phaseolus vulgaris) pela tecnica de high resolution magic angle spinning (HR-MAS)

Energy Technology Data Exchange (ETDEWEB)

Liao, Luciano Morais; Choze, Rafael; Cavalcante, Pedro Paulo Araujo; Santos, Suzana da Costa; Ferri, Pedro Henrique, E-mail: luciano@quimica.ufg.b [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Inst. de Quimica; Ferreira, Antonio Gilberto [Universidade Federal de Sao Carlos (UFScar), SP (Brazil). Dept. de Quimica

2010-07-01

The application of one-dimensional proton high-resolution magic angle spinning ({sup 1}H HR-MAS) NMR combined with a typical advantages of solid and liquid-state NMR techniques was used as input variables for the multivariate statistical analysis. In this paper, different cultivars of beans (Phaseolus vulgaris) developed and in development by EMBRAPA - Arroz e Feijao were analyzed by {sup 1}H HR-MAS, which have been demonstrated to be a valuable tool in its differentiation according chemical composition and avoid the manipulation of the samples as used in other techniques. (author)

Photoelectric photometry of the Am star HR = V423 Per

International Nuclear Information System (INIS)

Jerzykiewicz, M.

1989-01-01

This spectroscopic binary is the largest amplitude variable among Am stars. UBV observations of the star are presented. They show that in 1964 and 1965 it was constant in B and was only marginally variable in U. The hypothesis of the ellipsoidal variability of HR 976 is then discussed and found untenable. It is pointed out that this result may reopen the issue of light variability of Am stars. 10 refs., 2 figs., 2 tabs. (author)

Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A(®)) Following Acute Repeated Inhalation Exposure.

Science.gov (United States)

Roberts, Jenny R; Anderson, Stacey E; Kan, Hong; Krajnak, Kristine; Thompson, Janet A; Kenyon, Allison; Goldsmith, William T; McKinney, Walter; Frazer, David G; Jackson, Mark; Fedan, Jeffrey S

2014-01-01

Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m(3), five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution by day 7. In summary, acute

Sex- and Site-Specific Normative Data Curves for HR-pQCT.

Science.gov (United States)

Burt, Lauren A; Liang, Zhiying; Sajobi, Tolulope T; Hanley, David A; Boyd, Steven K

2016-11-01

The purpose of this study was to develop age-, site-, and sex-specific centile curves for common high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite-element (FE) parameters for males and females older than 16 years. Participants (n = 866) from the Calgary cohort of the Canadian Multicentre Osteoporosis Study (CaMos) between the ages of 16 and 98 years were included in this study. Participants' nondominant radius and left tibia were scanned using HR-pQCT. Standard and automated segmentation methods were performed and FE analysis estimated apparent bone strength. Centile curves were generated for males and females at the tibia and radius using the generalized additive models for location, scale, and shape (GAMLSS) package in R. After GAMLSS analysis, age-, sex-, and site-specific centiles (10th, 25th, 50th, 75th, 90th) for total bone mineral density and trabecular number as well as failure load have been calculated. Clinicians and researchers can use these reference curves as a tool to assess bone health and changes in bone quality. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine.

Directory of Open Access Journals (Sweden)

Hannah E Gavin

2017-01-01

Full Text Available Vibrio vulnificus causes highly lethal bacterial infections in which the Multifunctional Autoprocessing Repeats-in-Toxins (MARTX toxin product of the rtxA1 gene is a key virulence factor. MARTX toxins are secreted proteins up to 5208 amino acids in size. Conserved MARTX N- and C-terminal repeat regions work in concert to form pores in eukaryotic cell membranes, through which the toxin's central region of modular effector domains is translocated. Upon inositol hexakisphosphate-induced activation of the of the MARTX cysteine protease domain (CPD in the eukaryotic cytosol, effector domains are released from the holotoxin by autoproteolytic activity. We previously reported that the native MARTX toxin effector domain repertoire is dispensable for epithelial cellular necrosis in vitro, but essential for cell rounding and apoptosis prior to necrotic cell death. Here we use an intragastric mouse model to demonstrate that the effector domain region is required for bacterial virulence during intragastric infection. The MARTX effector domain region is essential for bacterial dissemination from the intestine, but dissemination occurs in the absence of overt intestinal tissue pathology. We employ an in vitro model of V. vulnificus interaction with polarized colonic epithelial cells to show that the MARTX effector domain region induces rapid intestinal barrier dysfunction and increased paracellular permeability prior to onset of cell lysis. Together, these results negate the inherent assumption that observations of necrosis in vitro directly predict bacterial virulence, and indicate a paradigm shift in our conceptual understanding of MARTX toxin function during intestinal infection. Results implicate the MARTX effector domain region in mediating early bacterial dissemination from the intestine to distal organs-a key step in V. vulnificus foodborne pathogenesis-even before onset of overt intestinal pathology.

Analysis of repeated measures data

CERN Document Server

Islam, M Ataharul

2017-01-01

This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

Are They Fit For Purpose? Exploring Managers' Experiences of UK HR Graduates & Employability Implications: A Pilot Study

OpenAIRE

Mullen, Emma

2014-01-01

The purpose of this research is to expand on existing understandings of graduate employability through exploring the lived experiences and perceptions of key informants, in this case, those with direct line management responsibilities for graduates. The context of this research is focused on Human Resources (HR) graduates, a discipline that has seen little qualitative inquiry across the Higher Education (HE), employability and HR literature, and which is currently dominated by skills-led appr...

Full-length model of the human galectin-4 and insights into dynamics of inter-domain communication

Science.gov (United States)

Rustiguel, Joane K.; Soares, Ricardo O. S.; Meisburger, Steve P.; Davis, Katherine M.; Malzbender, Kristina L.; Ando, Nozomi; Dias-Baruffi, Marcelo; Nonato, Maria Cristina

2016-09-01

Galectins are proteins involved in diverse cellular contexts due to their capacity to decipher and respond to the information encoded by β-galactoside sugars. In particular, human galectin-4, normally expressed in the healthy gastrointestinal tract, displays differential expression in cancerous tissues and is considered a potential drug target for liver and lung cancer. Galectin-4 is a tandem-repeat galectin characterized by two carbohydrate recognition domains connected by a linker-peptide. Despite their relevance to cell function and pathogenesis, structural characterization of full-length tandem-repeat galectins has remained elusive. Here, we investigate galectin-4 using X-ray crystallography, small- and wide-angle X-ray scattering, molecular modelling, molecular dynamics simulations, and differential scanning fluorimetry assays and describe for the first time a structural model for human galectin-4. Our results provide insight into the structural role of the linker-peptide and shed light on the dynamic characteristics of the mechanism of carbohydrate recognition among tandem-repeat galectins.

Stability of Routine Biochemical Analytes in Whole Blood and Plasma From Lithium Heparin Gel Tubes During 6-hr Storage.

Science.gov (United States)

Monneret, Denis; Godmer, Alexandre; Le Guen, Ronan; Bravetti, Clotilde; Emeraud, Cecile; Marteau, Anthony; Alkouri, Rana; Mestari, Fouzi; Dever, Sylvie; Imbert-Bismut, Françoise; Bonnefont-Rousselot, Dominique

2016-09-01

The stability of biochemical analytes has already been investigated, but results strongly differ depending on parameters, methodologies, and sample storage times. We investigated the stability for many biochemical parameters after different storage times of both whole blood and plasma, in order to define acceptable pre- and postcentrifugation delays in hospital laboratories. Twenty-four analytes were measured (Modular® Roche analyzer) in plasma obtained from blood collected into lithium heparin gel tubes, after 2-6 hr of storage at room temperature either before (n = 28: stability in whole blood) or after (n = 21: stability in plasma) centrifugation. Variations in concentrations were expressed as mean bias from baseline, using the analytical change limit (ACL%) or the reference change value (RCV%) as acceptance limit. In tubes stored before centrifugation, mean plasma concentrations significantly decreased after 3 hr for phosphorus (-6.1% [95% CI: -7.4 to -4.7%]; ACL 4.62%) and lactate dehydrogenase (LDH; -5.7% [95% CI: -7.4 to -4.1%]; ACL 5.17%), and slightly decreased after 6 hr for potassium (-2.9% [95% CI: -5.3 to -0.5%]; ACL 4.13%). In plasma stored after centrifugation, mean concentrations decreased after 6 hr for bicarbonates (-19.7% [95% CI: -22.9 to -16.5%]; ACL 15.4%), and moderately increased after 4 hr for LDH (+6.0% [95% CI: +4.3 to +7.6%]; ACL 5.17%). Based on RCV, all the analytes can be considered stable up to 6 hr, whether before or after centrifugation. This study proposes acceptable delays for most biochemical tests on lithium heparin gel tubes arriving at the laboratory or needing to be reanalyzed. © 2016 Wiley Periodicals, Inc.

HIV-1 replication through hHR23A-mediated interaction of Vpr with 26S proteasome.